The LDKT scheme is needed for several reasons. Firstly, this is due to the benefits it offers recipients in comparison with deceased donor KT. LDKT is also necessary if we are to progress towards transplantation self-sufficiency, as it would be hard to meet the needs for KT in our population given the gradual change in the profile of deceased donors. Finally, the decision to implement this scheme is based on a substantial improvement in the procedure for donors.

LDKT is associated with better long-term results than deceased donor KT, regardless of the genetic relationship between the donor and recipient6,12 or whether it is a first or second transplantation.13 European Registry of Renal Replacement Therapy data (ERA-EDTA) show a renal graft survival rate (adjusted for age, sex and cause of primary renal disease) of 86.7% at 5 years for living donor recipients, as opposed to 81.4% for deceased donor recipients. Patient survival rates at 5 years (adjusted for age, sex and cause of primary renal disease) are 94.6% and 92.1%, respectively.14 American Registry data show very similar results to those of the European Registry.15

Different reasons have been suggested for the better results obtained with LDKT, including good living donor basal health, with less associated pathology than deceased donors.1 However, no significant differences are found in mid-term survival or the incidence of acute rejection when the results of deceased donor KT are compared with those of standard living donors in patients with similar characteristics. Nevertheless, there is a significant difference in graft function delay.16 These differences in favour of living donation are significant when the overall results of LDKT are compared with those corresponding to deceased donors, without differentiating deceased donor type (brain death or asystole, and standard or expanded criteria).6,13,17

On the other hand, LDKT is performed more often than deceased donor transplantation before the patient commences renal replacement therapy with dialysis 18. It has to be underlined that long-term dialysis and its associated comorbidity have repeatedly been identified as factors which have a negative association with transplanted graft and patient survival, regardless of chronic renal failure aetiology 19,20.

Based on current evidence, the better results achieved with LDKT are therefore fundamentally due to transplant recipient characteristics and degree of comorbidity, the delay until transplantation and donor profile.

Road and industrial safety laws have changed fundamentally in Spain over the last 20 years, and there has also been a continuous improvement in medical care. These factors have given rise to a fortunate decrease in the mortality of the population, although this has also caused a gradual fall in potential donations due to brain death 21.

Thanks to its transplant coordination network and medical and surgical teams, our system has adapted to this new scenario. However, although this has increased the number of transplantations, it has also involved a substantial change in donor profile.

The changes in end-of-life care for critical patients have continued, with the unprecedented development of controlled asystole donation programmes 16,22. Successful organ transplants from elderly and very elderly donors now occur regularly, adapting to potential older donors with associated comorbidities. The implementation of projects such as the one for non-standard risk donors 23,24 and the preparation of clinical guides 25–28 to ensure appropriate evaluation of the risk-benefit of transplanting organs from donors with different pathologies, have made it possible to gradually broaden the degree of acceptance and subsequent use of organs from more complex donors.

It is within this context that Spain achieved its highest ever rate of KT and the highest in the world, with 72.8 transplants pmp in 2019 29. Nevertheless, in spite of the fact that the transplantation waiting list shortens year after year, at the end of 2019 it still stood at 3.933 patients, so we are still a long way from becoming self-sufficient. When examining the negative effect of the time spent in dialysis on post-transplantation survival, we find that only 5% of ESRD patients were transplanted before starting treatment with dialysis 30.

The increase in deceased donors has occurred due to the ongoing rise in the number of progressively older donors, including those in controlled asystole. This makes it unlikely that young patients with end stage renal failure will be transplanted after only a short delay. Although this population segment may benefit more clearly from living renal donation, this therapy is suitable for patients in any age band.

It has to be pointed out that the scarcity of young donors also affects the availability of other organs, such as the pancreas. Very briefly, diabetic patients compete against potential young recipients for young kidneys. They all seek an appropriate donor in terms of age, especially in the case of highly sensitized patients. LDKT may help to resolve this situation by occasionally offering the possibility of pancreas transplant.

Although the benefit of LDKT for patients is clear, this therapy could not be used without the sine qua non condition of guaranteeing donor safety. Each chapter of this clinical guide therefore takes into account the possible consequences for donors and their subsequent quality of life.

The standardization of the evaluation and care of living donors 1,31, as well as the use of increasingly less invasive nephrectomy techniques 32, have the primordial aim of protecting donor health 1,8,9.

Although performing a nephrectomy in a healthy individual is not innocuous, the risk of immediate mortality associated with living renal donation is estimated to stand at 0.03%, and this has not varied in the last 15 years 33. The introduction of laparoscopic nephrectomy has led to a considerable improvement in the immediate postoperative period, and donors recover and recommence their social and professional lives sooner. Although the probability of a living renal donor developing renal disease over the long-term is lower than the figure for the general population (where comorbidity is a factor), it is still higher than it would have been if the donor had not been subjected to nephrectomy 34–37. Age, African American, obesity and familial genetic diseases have been shown to be risk factors in long-term donor evolution. It is therefore necessary to evaluate donor risk and take these factors into account, in the information supplied to donors and recipients as well as in donor care after the procedure 9.

A LDKT scheme has to be based on the fundamental principle of complete protection of the living organ donor. The basic principles of this protection are contained in different international legal documents: the WHO Guiding Principles on Human Cell, Tissue and Organ Transplantation, the Council of Europe Convention on Human Rights and Biomedicine, as well as its Additional Protocol concerning Transplantation of Organs and Tissues of Human Origin, and Directive 2010/53/EU of the European Parliament and the Council, of 7 July 2010, on the Standards of Quality and Safety of Human Organs intended for Transplantation38–40. In Spain these principles are expressed in Law 30/1979, of 27 October, on organ harvesting and transplantation, and in Royal Decree 1723/2012, of 28 December, which governs the Activities of Obtaining, Clinical Use and Territorial Coordination of Human Organs intended for Transplantation, establishing Quality and Safety Requisites 41. Apart from this national and international legislative framework there are also national professional standards 1, such as this Guide, and international ones, especially the KDIGO guides 9.

The protection of a living donor starts with the appropriate evaluation and selection of a potential candidate, based on medical and psychosocial criteria 8. Prospective donors should be subjected to an exhaustive standardized evaluation of their potential as such to assess the risk that donation would involve for their state of health–as well as for the potential recipient of the donated organ. Risk assessment covers aspects of psychosocial as well as physical health, enabling the identification of absolute or relative contraindications to donation.

The public health system acquires a responsibility towards living donors, because of the complications they may develop over the short, medium or long-term. It is therefore obligatory to ensure living donors have continuous medical protection and care to preserve their residual renal function (in the case of renal donors) while treating any possible complications deriving from donation. Within the European Union it is also obligatory to record information about each living donor in national registries designed to show their basal clinical and demographic characteristics and evolution, including any complications associated with the donation process. Apart from recording this information, it is also obligatory for medical workers to notify the National Biovigilance System 42 of any adverse events (donation incidents that place a living donor at risk, even if no harm was caused) and adverse reactions (incidents that harmed a living donor).

Determining the validity of the consent to donate is a basic part of evaluating a living donor. A valid consent must be freely given, informed and clearly expressed. When evaluating a living donor it is fundamental to elucidate the underlying reasons for the donation, and to evaluate the legitimacy of the relationship between the potential donor and the recipient. Information about the process should be broad in scope, structured and comprehensible. The possibility of discontinuing the process at any time and without the need for any explanation whatsoever should be expressed. The living donor advocate plays a fundamental role in determining the validity of consent: this professional is unconnected with the individuals who are going to perform the harvesting and engraftation of the organ, and they work to ensure the complete protection of the person. In our country this role is fulfilled by the intervention of an independent medical professional, while the Ethics Committee of the hospital in question also participates, and the potential donor has to appear before the Examining Magistrate. This three-filter system established by our legislation is probably one of the strongest safeguards in the world within this context. The donation procedure must be halted if situations which lead to suspicions of human trafficking or other comparable scenarios are identified. The relevant authorities should also be notified, to activate investigations and prosecute any possible crimes.

The protection of living donors also involves the elimination of disincentives against donating organs while alive. These include reimbursing any expenses incurred by the donor and compensation for loss of earnings due to the assessment, surgical operation and subsequent recuperation. Another example of measures to be applied would be protection against loss of employment due to time off work for diagnostic tests or the act of donation itself.

In spite of the strong international consensus in favour of LDKT, this treatment did not become widespread in Spain until the early years of the 21st century. This was partially because of the success of the Spanish model of donation and transplantation 43, and partially because clinicians did not wish to perform a nephrectomy on healthy individuals 44,45.

Given the agreement reached in the Amsterdam Forum, the international stance regarding donor protection and the good results obtained with this therapy in major international registries 8,33,46,47, LDKT started to be advocated in different areas (transplantation teams, scientific societies, patient associations, regional transplantation coordination bodies and the ONT) 48. Work was undertaken to raise awareness of this therapy among patients and their families: the benefits it offers patients, the type of assessment donors are subjected to and the possible consequences of donation for them 1. Major efforts were also made to train the clinicians involved in this activity.

The implementation of a national registry was fundamental in Spain to show the possible consequences of living donation. This registry includes data on the main clinical and epidemiological characteristics of living renal donors, the nephrectomy techniques used, their complication rates and the possible clinical implications of renal donation over the short-, medium- and long-terms. This registry started working in 2010 and, thanks to the commitment of administrative bodies and clinicians, it now contains information on 96% of living renal donors. It makes it possible to extract reliable conclusions, so that it is used to assess donor risk as well as supplying information they are given about the procedure.

These measures have driven the emergence of new LDKT schemes and increased activity in existing ones. While 61 LDKT were performed in 12 hospitals in 2004, more than 300 procedures in 33 accredited hospitals were performed in 2019, corresponding to an activity of 7.1 transplantations pmp 29 (Figure 2). Although this is good news, it is important to reflect that, in spite of the increase in activity, we are still a long way from achieving the aim of preventing many patients from having to enter dialysis. When LDKT over recent years in Spain is compared with the situation in other nearby countries or ones in similar sociodemographic and economic circumstances, we find a lower rate of activity than is the case in the Scandinavian countries, the Netherlands, the United Kingdom, the United States (U.S.A.) or Canada 49. A slight fall in recent years is a striking finding in the U.S.A., although this has been analysed by the system there and has now been reversed (Figure 3).

Figure 2.

Living donor kidney transplantation in Spain. Absolute number of kidney transplantations and rate per million population (pmp). Source: National Transplantation Organization.

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Figure 3.

Evolution of the rate of living donor kidney transplantations per million population in different countries. Years: 2009-2018. Source: Global Observatory on Donation and Transplantation.

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Nor has transplantation activity increased uniformly throughout Spain. There are large differences between the numbers of LDKT procedures pmp performed in the different Autonomous Communities, leading to unequal access to this therapeutic option (Figure 4). Several of the Communities with the highest rates of LDKT pmp also have high rates of deceased donor KT pmp. LDKT activity in Catalonia and Galicia is similar to that registered in a country as active in this field as the United Kingdom 49.

Figure 4.

Renal transplantations per million population (pmp) according to donor type and Autonomous Community. Spain 2019. Source: National Transplantation Organization.

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Standard LDKT takes place between a donor and recipient who are blood group and HLA compatible. One of the advantages of living as opposed to deceased donation is that as it often takes place between blood relatives, there is a higher probability that donor and recipient will share a higher number of antigens. Nevertheless, this fact has not prevented LDKT taking place between genetically unrelated individuals, with excellent results 50. This favours the increasing use of transplantation between couples, friends and unrelated individuals, as occurs in paired and altruistic renal donation programmes 51.

The increase in living donation has led to a rise in the number of potential donor assessments which detect incompatibility with the recipient. In fact, from 30% to 40% of potential donors who are evaluated are found to be incompatible with their recipient. This may be due to blood group incompatibility, the presence of hemagglutinins against the donor's blood group, or the detection in the recipient of specific antibodies against the HLA of their donor. Different strategies have been used to overcome incompatibility: some of them are based on desensitizing the recipient so that direct incompatible transplants can be used (ABO or HLA incompatible) 52–54 while others use donor interchange within a pool of incompatible pairs, known as pooled or paired transplantation 51,55,56. Both strategies have been used in Spain for more than 10 years, enabling LDKT for approximately 50 patients per year 29 who would otherwise have remained on the waiting list for a deceased donor.

Adapting the LDKT scheme is not solely based on overcoming incompatibility, as it also involves broadening donor acceptance criteria in terms of cardiovascular risk factors, as well as donor and recipient age. Respecting the former, and always with donor protection as the core aim, the number of donors with pharmacologically-controlled arterial hypertension (hypertension) has risen over recent years. This is also the case for patients with obesity (defined as a BMI≥30 Kg/m2), and these donors now amount to 10% and 16% of live renal donors, respectively 57.

Respecting age, according to Spanish Registry of Renal Patients (REER) data, annual post-transplantation mortality is lower than that of those patients of all age groups who remain in dialysis 30, so that LDKT is also an excellent option for the oldest group of patients. In fact, in Spain 16% of LDKT recipients are above 60 years old, as are 21% of donors, with good post-donation evolution 57.

The national LDKT scheme over recent years has gradually improved in quantitative terms, with an increasing number of transplantations. It has also improved qualitatively, thanks to better knowledge of the process and its results, increasingly systematic information about this therapy and the overcoming of technical obstacles against transplantations of this type. Nevertheless, several challenges still have to be faced, and these are described in the National Organ Donation and Transplantation Strategy for 2018-2022 58.

Insufficient LDKT activity and the differences between hospitals and Autonomous Communities mean that a strategy of identifying and spreading good practices is necessary. This is so for the organization and development of living donor information and assessment, as well as selection processes in terms of immunology, nephrology, urology and psychosocial aspects. Good practices should also be identified and shared regarding the surgical procedure for the donor and their care and follow-up. The ONT, the SEN and the SET have therefore led a benchmarking project which will produce specific recommendations to be adopted by hospitals and clinicians to improve critical areas within the LDKT process. It is important to always supply information about LDKT in ESRD consultations. The position in charge of coordinating LDKT activity in accredited hospitals should be identified, and ad hoc training actions for the teams and clinicians who are able to prescribe this renal replacement therapy have to be developed.

Measures to protect living donors have to be improved in our country, including those which apply to social and work-related factors that require reforms which are already being prepared. The introduction of technical improvements in the national paired KT, altruistic donation and incompatible donor schemes will also make it possible to increase the number of patients who are able to benefit from LDKT with suitable post-transplantation results.

Finally, the need to reach clinicians in an effective way is one of the reasons why the SEN, the SET and the ONT decided to prepare this LDKT recommendations document.

This regulation replaces Royal Decree 2070/1999, of 30 December, which had been in force since it repealed the Decree of 22 February 1980, which had been developed for the first time by Law 30/79. Throughout its existence the law has undergone these three regulatory developments, of which the modification that occurred in 1999 was especially relevant in the field of cadaveric organ donation. The regulatory reforms have not altered the living donor donation regime, although this does not mean that new forms of donation, such as altruistic donation, are excluded from the scope of coverage of the current regulation.

The Royal Decree that is currently in force incorporates in Spanish legal code Directive 2010/53/EU of the European Parliament and Council, of 7 July 2010, on quality and safety standards for human organs destined for transplant. The Directive determines the minimum requisites that have to be applied when donating, evaluating, characterising, obtaining, preserving, transporting and transplanting human organs, with the purpose of guaranteeing high levels of quality and safety for the said organs. It also sets requisites for traceability and the development of a system for the notification and management of events and severe adverse reactions, establishing the minimum data that have to be recorded for the evaluation of donors and organs.

Its outstanding ethical foundations include those which refer to the voluntary and free nature of donation, together with consent, the protection of living donors and personal data protection. For the first time it also introduces a list of administrative infractions due to failure to comply with the regulations governing the harvesting and transplantation of organs.

Observing the requisites and principles established in the Directive, RD 1723/2012 sets quality and safety requisites for activities connected with obtaining and clinically using human organs, with the aim of guaranteeing a high level of human health protection and reducing the loss of available organs as far as possible.

Law 30/79 states that the purpose of the said activities has to be therapeutic. That is, they should be guided by the sole purpose of favouring the health or conditions of life of the recipient, without prejudice to any research that may also be taking place. The exercise of these activities also has to respect the fundamental rights of persons and the ethical postulates applied to clinical practice and biomedical research.

The principles of the regulation contained in the Royal Decree are based on Law 30/79, which develops Organic Law 3/2018, of 5 December, on Personal Data Protection and the guarantee of digital rights. They are also based on Directive 2010/53/EU, which transposes them, and they are listed below:

- Confidentiality: this principle prohibits the communication of data that would make it possible to identify the donor and recipient. The exception to this rule are those cases in which an individual publicly, freely and voluntarily identifies herself as a donor or recipient. Even when this occurs, the principle should be respected that neither donors nor their family members may know the identity of the recipient or their family members, and vice versa.

In general, any diffusion of information that may directly connect obtaining an organ and its subsequent transplantation is to be avoided. However, this restriction is not applicable to the parties directly involved in the transplantation of organs from a living donor between individuals who are genetically related or connected by kinship or close friendship. Outside such cases, the principle of confidentiality should be respected even in the case of living donor organ transplantation.

Respecting this principle does not prevent taking preventive measures when the existence of an individual or collective risk to health is suspected.

- Personal data protection: information on human organ donors and recipients is to be recorded, processed and stored in the strictest confidentiality, according to the stipulations of data protection laws, in the General Health Law and in Law 41/2002, of 14 November, which governs patient autonomy and rights and obligations in the field of information and clinical documentation.

The individual in charge of the therapy will have to adopt the technical and organizational measures necessary to guarantee the security of the data in this special category, preventing their alteration, loss, processing or unauthorized access. The individual in charge as well as the person in charge of processing are obliged to keep professional secrecy, even after their professional relationship has ceased. Infractions in this area may be penalized by the Spanish Data Protection Agency, without prejudice to any criminal responsibility that may be incurred (articles 197 and 198 of the Penal Code).

According to article 9 of Organic Law 3/2018 on Personal Data Protection and the guarantee of digital rights, by reference to article 9.2 of Regulation (EU) 2016/679, data processing in the field of health may be supported when this is required by the management of healthcare, social, public and private systems, or the execution of an insurance contract which covers the affected party.

- Limitation of Promotion and Publicity: the promotion of organ donation activity should take place in general terms, underlining its altruistic, voluntary and selfless nature. It will not be possible to advertise the donation of organs to benefit specific individuals or certain hospitals, institutions, foundations or companies.

Deceitful advertising which leads to erroneous opinions on obtaining human organs and using them clinically is expressly prohibited.

Without prejudice to the foregoing point, the competent authorities will promote the information and education of the population regarding donation and transplantation, the benefits these offer to those who need them, as well as the conditions, requisites and guarantees which apply to them.

- Free of charge: it is not possible for the donor or any other physical person or legal entity to receive any reward or economic compensation whatsoever for donation. Nor will the recipient be subjected to any demand for any payment whatsoever for the transplanted organ, and nor is it possible to offer or deliver any economic benefits or benefits of any other type in connection with the assignation of one or several organs for transplantation, and nor is it possible to request them or accept such benefits. All advertising regarding the need for an organ or the availability of one is also prohibited, as is offering or seeking any type of reward or remuneration.

The Royal Decree reproduces the exception for the compensation of economic losses when it indicates that the performance of the medical procedures associated with obtaining an organ shall not, in any case, be at the expense of the living donor. Living donors are not to be prevented from receiving repayment of their expenses and compensation for any reduction in income directly associated with the donation. However, when the said repayment is applicable, it will necessarily have to be made using the mechanisms which may be supplied for this purpose by the competent authorities.

• -

  Fairness: the selection of and access to possible recipients should be subject to criteria of fairness, guaranteeing equality of opportunities for the therapy.

• -

  Adoption of the quality and safety measures which are necessary to reduce the loss of organs, minimise possible risks and attempt to ensure the maximum possibilities of success for transplantation, improving the efficiency of the process of obtaining and transplanting organs.

Respecting the specific regulation of donation of this type, it is governed by article 8 in a form that is consistent with the regulation contained in law 30/79, but more completely developed. Living donation is subject to the following requisites:

• 1.

  The harvesting should be of an organ or part of the same whose absence is compatible with life and whose function can be compensated by the donor's organism appropriately and sufficiently safely.

• 2.

  It will not be possible to harvest organs from minors, even with the consent of their parents or tutors.

• 3.

  Nor will it be possible to harvest - or, if applicable, to use - organs from a living donor when:

• -

  For any reason it may be considered that consent was obtained due to an economic conditioning factor or one of any other type, social or psychological.

• -

  There are suspicions that the free consent of the donor has been altered.

• -

  Sufficient possibilities of transplant success are not expected.

• 4.

  The right to information should include the planned procedure for the possible case in which after harvesting of the organ it cannot be transplanted in the recipient for whom it was intended. All information should be supplied to the donor in appropriate formats, so that it is accessible and comprehensible for persons with disability.

• 5.

  It will be mandatory for the Ethics Committee of the transplanting hospital to issue a report.

Accreditation of the state of health and mental faculties of the donor is a requisite demanded by Law 30/79. The Royal Decree stipulates that this accreditation should be by a doctor other than the one who will perform the harvesting, after being supplied with the corresponding information. This information will necessarily include the following aspects: a) inherent risks of the intervention, b) foreseeable physical and or psychological consequences, c) possible repercussions in their personal, family or professional life, and d) expected benefits of the transplantation and the potential risks for the recipient. The living donor should also be informed of the need for them to communicate their medical history, and they will be informed that they will be given medical care for their recovery and will be clinically followed-up in connection with the harvesting of the organ.

The above points will be accredited in a medical certificate which describes the donor's state of health, the information that was supplied and the donor's freely expressed response and motivations and, if applicable, any sign of external pressure on the same. This certificate will include the list of the names of the other clinicians who have helped the certifying doctor in the tasks involved.

Article 10 of the Royal Decree lists the general requisites which living donor organ removal hospitals have to fulfil, following authorization by the competent authority of the Autonomous Community:

• 1)

  It should be authorized as a deceased-donor organ removal hospital and as an organ transplantation hospital for which living-donor organ removal authorization is requested. Article 11.2 RD 1723/2012.2.

To be authorized, deceased-donor organ removal hospitals must fulfil at least the following requisites:

• a)

  They must have an organization and working regime which makes it possible to ensure that organ removal is performed in a satisfactory manner;

• b)

  They must have a hospital transplantation coordination unit with the appropriate personnel and material resources;

• c)

  They must guarantee the availability of qualified medical personnel and the technical means of verifying death;

• d)

  They must guarantee the availability of duly qualified medical and nursing personnel, as well as sufficient medical services and technical resources for the correct selection, evaluation, description and care of the donor;

• e)

  They must guarantee the availability of appropriate medical services, including laboratories and imaging techniques, to carry out the determinations that are considered necessary at any time and which permit appropriate clinical assessment of the donor. These services will be staffed by qualified personnel and will have appropriate facilities and equipment;

• f)

  They must guarantee the availability of the facilities and materials which are necessary for the correct performance of organ removal, according to the accepted standards in this field and the best medical practices;

• g)

  They must have framework programmes which guarantee the quality and safety of the whole process;

• h)

  They must have a confidential registry with restricted access, with its corresponding alphanumerical codes, to record the necessary data that makes it possible to ensure traceability, as well as to link the traceability of the tissues and cells obtained from donors;

• i)

  They must keep a donor serum deposit during a period of at least ten years, for the purpose of performing biological controls, if necessary;

• j)

  They must guarantee the availability of the appropriate personnel, facilities and services for the restoration of the body of the deceased person, after removal;

• k)

  They must comply with the requisites established for confidentiality and the protection of personal data, together with the promotion, publicity and free nature of donations.

• 1)

  They must have sufficient medical and nursing personnel with qualifications and accredited experience for correct donor assessment and selection and the performance of the removal.

• 2)

  They must have sufficient facilities and materials necessary for the correct performance of organ removal, according to the accepted standards within this field and the best medical practices.

• 3)

  They must have the medical services, including laboratories and imaging techniques, which are necessary to ensure the proper preoperative study of donors and to treat any complications which may arise in them. These medical services are to be staffed by qualified personnel and they are to have appropriate facilities and equipment.

• 4)

  They must have protocols which ensure appropriate donor assessment and selection, communicating relevant information about the donor and recipient when harvesting and transplant are not performed in the same hospital, as well as protocols for the process of organ removal and the immediate postoperative and long-term follow-up, together with other protocols or framework programmes with the aim of ensuring the quality and safety of the whole process.

• 5)

  They must have a confidential registry with restricted access and its corresponding alphanumerical codes, to record the necessary data that makes it possible to ensure traceability.

• 6)

  They must guarantee recording of information about living donors and their clinical follow-up, according to the stipulations of article 31, without prejudice to the regulations on the protection of personal data and statistical confidentiality. Article 31, on information systems, establishes:

• i.

  Without infringing the agreements that may be established with relevant professional and scientific associations or the systems that may be implemented by the autonomous communities for such purposes, and in cooperation with the same, the National Transplant Organization will develop and Maintain the state information systems that will record and store the data relating to: a) Donors and organs and their description; b) Organ traceability from their donation to transplantation or rejection and vice versa; c) The characteristics and movements of the patients included in the waiting list for transplantation; d) The characteristics and follow-up data of transplanted patients; e) The characteristics and follow-up data of living donors; f) Notification and measures used to manage events and severe adverse reactions.

• ii.

  For each one of the above sections, the National Transplant Organization will define, in cooperation with the autonomous communities, the minimum data that will have to be supplied to the state system for each donor, organ, patient in a waiting list or recipient.

• 7)

  They must comply with the established requisites regarding confidentiality and personal data protection, promotion and advertising and the free nature of donations.

The procedure for obtaining medical authorization from the corresponding autonomous community, as well as renewing or cancelling the same, without prejudice to the specific regulation in each one of the said communities, will follow the instructions of article 11 of RD 1723/2012 on authorising hospitals to remove the organs of deceased donors. This authorization must contain at least the following: a) the activity for which the hospital is authorized; b) The name(s) of the person(s) in charge of the removal process; c) The duration of the authorization, depending on the period during which it will be in force as determined by the competent authority.

When the authorization expires it may be renewed after checking that the conditions which made it possible continue. In no case may it be understood to have been renewed automatically.

Any form of substantial modification which occurs in the conditions, structure, persons in charge or working of the hospital should be reported to the competent authority, and it may give rise to review of the medical authorization or even to the cancellation of the same, even before the end of the period during which it would be in force.

The authorization will specify the person who, as well as being in charge of the medical unit in which the transplant will take place, has to approve each intervention, and this may be revoked or suspended as a result of inspection and checks by the competent authorities.

Respecting organ transplantation hospitals, article 19 of the Royal Decree stipulates, as well as the general requisites established for the hospitals where organs are removed, that the minimum specific requisites shown in appendix II will apply. To carry out any transplantation of organs from a living donor it will be indispensable that the hospital be authorized for the transplantation of the corresponding organ from a deceased donor, proving accredited experience in this intervention. Section 1 of article 18 of RD 1723/2012 states that human organ transplantation may only be performed in those hospitals which hold the specific authorization of the competent authority in their corresponding autonomous community. In section 2 it states that to be authorized, a human organ transplantation hospital must fulfil at least the following general requisites:

• a)

  It must be authorized as a hospital for obtaining the organs of deceased donors and accredited with sufficient activity to guarantee the viability and quality of the transplantation scheme.

• b)

  It must have a medical organization and working regime that are appropriate for performing the requested intervention.

• c)

  It must have the corresponding medical and surgical unit with sufficient medical personnel and have proven experience in the type of transplantation in question.

• d)

  It must guarantee the availability of specialist doctors with proven experience in the diagnosis and treatment of complications arising from the transplantation that is to be performed.

• e)

  It must have a hospital transplantation coordination unit.

• f)

  It must have the facilities and materials which are necessary for the appropriate performance of the transplantation process, in the preoperative stage, during the intervention and in the postoperative stage, according to the accepted standards in this field and the best medical practices.

• g)

  It must have the medical departments, including laboratories and imaging techniques, which are necessary to guarantee the performance of the transplantation, appropriate clinical follow-up of the recipient and the correct treatment of the possible complications which practising the type of transplantation in question requires. These medical services will have qualified staff and the appropriate equipment and facilities.

• h)

  It must have a pathological anatomy department with the necessary human and technical resources for the study of complications associated with transplantation and carrying out possible post-mortem studies.

• i)

  It must have a microbiology laboratory which is able to undertake checks of the infectious complications patients may suffer.

• j)

  It must guarantee the availability of an immunology laboratory and a histocompatibility unit with the technical and human resources which are necessary to guarantee the correct performance of the immunological studies which are necessary for pre- and post-transplantation monitoring.

• k)

  It must have a Transplantation Commission and the protocols to ensure the appropriate selection of recipients, the transplantation process and immediate and long-term postoperative follow-up, and to guarantee the quality and safety of the whole therapeutic process, as well as other quality and safety protocols.

• l)

  It must have a confidential registry with its corresponding alphanumerical codes, with records of the transplantations performed and the data that are necessary to guarantee traceability.

• m)

  It must guarantee registration of the information that makes it possible to evaluate the transplantation activity undertaken in the hospital, as well as the results obtained, according to the stipulations of article 31 and without prejudice to the regulations governing the protection of personal data and statistical confidentiality.

• n)

  At all times it should ensure that the actions and resources of the medical units involved in different types of transplantation are appropriate for the state of the art in science, using up-to-date diagnostic and therapeutic protocols.

• o)

  It must comply with the established requisites in the field of confidentiality and personal data protection, promotion and advertising and the free nature of donations.*

The procedure to obtain authorization by the corresponding autonomous community will commence with an application that should contain at least the following data: a) The type of transplantation to be performed. b) The list of doctors who are in charge of the transplantation team, as well as the documentation which accredits their qualifications, and c) A report with the detailed description of the human and material resources and the protocols which the hospital has, according to the requisites for undertaking the corresponding activity.

Without prejudice to the specific regulations of each autonomous community, the authorization should contain at least the following: a) the type of transplantation for which the hospital is authorized. b) The name(s) of the person(s) in charge of the transplantation team, and c) the duration of the authorization, according to the period it will be in force as determined by the competent authority.

It will be the responsibility of each autonomous community to inspect or supervise transplantation coordination units, organ removal hospitals and transplantation hospitals at regular intervals. For this purpose, units and hospitals should supply all of the information in the format and way which may be requested, in connection with the activity for which they have been authorized.

Article 32 of the Royal Decree governs the information systems that have to be implemented for the registration and custody of certain data. These are data on: a) The donors and the organs, and their description. b) The traceability of organs from donation until transplantation or rejection and vice versa. c) The characteristics and movements of the patients included in the transplantation waiting list. d) The characteristics and follow-up data of transplanted patients. e) The characteristics and follow-up data of living donors, and f) Notification and measures taken in the case of severe events and adverse reactions.

The National Transplant Organization has the function of developing and maintaining the state information systems in which the said data are registered and stored, in cooperation with the autonomous communities and without infringing on the systems the latter may develop and the agreements which may be entered into with the relevant professional and scientific associations.

In cooperation with the autonomous communities, the National Transplant Organization will establish the minimum data which will have to be supplied to the state system for each donor, organ, waiting list patient or recipient. The state information systems, which will have to permit regular statistical analyses, will receive data from the hospitals where organs are obtained or transplanted, as appropriate, either directly or through the available autonomous community systems. The National Transplant Organization will establish, in cooperation with the autonomous communities, the procedures that will make it possible for the state to compile the information.

With the data included in the systems, and without prejudice to other reports that may be prepared, the National Transplant Organization will prepare annual reports on the activity undertaken in hospitals where organs are obtained and transplanted throughout national territory, including aggregated data on living and deceased donors, the number and type of organs obtained and those which were transplanted or rejected. These reports will never contain the personal data of donors or recipients, and they will be supplied to the transplantation coordination network and the transplantation teams, and they will be publically accessible.

As well as permitting general use of the data in question, state information systems may also be used by hospital or autonomous community information systems for their own data, when the corresponding autonomous community or hospital requires this.

Access to any of the data contained in the information systems will be restricted to authorized persons in hospitals, autonomous community coordination units or in the National Transplant Organization, and all of the systems at hospital, autonomous community or state level will comply with the current regulations on personal data protection, confidentiality and statistical secrecy.

Law 30/79 refers to the development of regulations governing the granting of donor consent, as well as determining the authority before which consent must be granted. In Royal Decree 426/1980, of 22 February, and until RD 1723/2012 came into force, the regulations of the sector stipulated that consent had to be granted before a judge, and more specifically, the judge in charge of the Civil Registry. The second additional Regulation of Law 20/2011, of 21 July, on the Civil Registry, when it refers to the legal regime of the person In Charge of the Central Civil Registry Office and the General Civil Registry Offices, states that the posts of being in charge of Civil Registries were to be filled by career civil servants in Subgroup A1 who held a degree in Law or the university qualification which had replaced this, and the legal secretaries (now justice administration lawyers). Thus the legislator ordered the Civil Registry to be more independent of the judicial system, turning it into an administrative organ which was no longer under the control of a judge. In connection with the said legal project, RD 1723/2012 tried to keep to the same line as the previous regulations, stating that the authority before which donors had to give their consent was still a judicial authority. Nevertheless, given the legal plan to make civil registries independent of the judiciary, the Royal Decree attributed the competence to the examining magistrate. This also agrees with the project for the Law of Voluntary Jurisdiction, which was being processed at the time and is now in force (Law 15/2015, of 2 July, on Voluntary Jurisdiction).

The report issued by the General Council of Judicial Power on the project for Royal Decree 1723/2012 found in favour of the maintenance of judicial intervention in case of living donation, as it proved that the introduced reform is not “less important, or a trivial question, as the legal modification which made the Civil Registry independent of the judiciary involves, respecting the purposes of this report, the disappearance of the jurisdictional guarantee of the rights, in this case, of the freedom of a living donor to give consent, and the awareness of the same of the importance and repercussions of their decision (definitively, that they have the information that is necessary to freely give their consent), which had been conferred by the Judge in charge of the Civil Registry, and which cannot be substituted by the civil servant who is in charge of the Civil Registry, according to the model established in Law 20/2011”.

It is true that the civil registries have not become independent of the judiciary. Royal Decree-law 16/2020, of 28 April, on the organizational and procedural measures to combat COVID-19 within the context of the Legal Administration, modifies the final tenth regulation of Law 20/2011, of 21 July, on the Civil Registry, and stipulates that the same will come into force on 30 April 2021.

In any case the authority for giving consent is now definitively held by the examining magistrate of the court of first instance which exists in each judicial administrative area, with jurisdiction over the entire territory of the same and with its seat in its capital, who is the authority on recognition in civil law procedures, including procedures of voluntary jurisdiction.

The procedure which must be followed to obtain living donor organs requires the presentation, before the court of first instance of the locality where the harvesting or transplantation is to take place, as selected by the promotor of the proceedings, of a request by the donor or a communication by the director of the medical centre where this will be carried out, or the delegated individual, describing the personal and familial circumstances of the donor, the purpose of the donation, the medical centre where harvesting is to take place and the identity of the doctor in charge of the transplant, all this accompanied by the medical certificate referring to the mental and physical health of the donor.

The donor must give their express consent before the judge during the appearance that takes place in the voluntary jurisdiction proceedings (which require the intervention of a legal body for the tutelage of rights and interests, without any controversy or conflict which would have to take the form of litigation) and which commences, following the explanations of the doctor who is to carry out the harvesting and in the presence of the doctor who accredits the physical and mental health of the donor, the doctor in charge of the transplantation and the person who has to approve the intervention, according to the document which authorises the harvesting of organs in question.

The document transferring the organ where the donor expresses their agreement will be issued by the Judge and signed by the donor, the doctor who is to execute the harvesting and the others who are present. If any of the former doubt that consent was given expressly, freely, consciously and selflessly, they may effectively oppose the donation. A copy of this transference document will be given to the donor. In no case may organs be obtained without this document being signed beforehand.

To confirm that the consent of the donor is firm, the legislators set a period of at least twenty four hours from the moment the organ transfer document is signed to the moment of harvesting, during which the donor is able to revoke their consent at any time prior to the intervention without the need for any formality whatsoever. The said revocation may not give rise to compensation of any type.

In any case and prior to the presentation of the request to appear before the court of first instance, the potential donor will have signed an informed consent document in which they declare that they were sufficiently informed duly in advance of the proceedings to which they would be subjected, as well as the risks, possible complications, expected benefits and alternatives, with the possibility of asking all of the questions they considered to be appropriate and stating that all of their questions had been answered.

Voluntary Jurisdiction Law 15/2015, of 2 July, considers the giving of consent for the donation of organs by a living donor to be one of the acts in which a judge has to take part, for the effective tutelage of their rights and interests under civil law. The publication of this regulation, apart from establishing the legal procedure to follow to formalise consent for donation, does not modify the legal regime created by Royal Decree 1723/2012.

Articles 78, 79 and 80 (Chapter X under the heading “On the harvesting of organs from living donors”) of this Law centre on regulating this area, and they always consider that the judicial intervention has the sole aim of verifying that the consent of the donor is given freely, voluntarily, selflessly and that is complies with the other requisites of Law 30/79 and the resulting regulations.

The law stipulates that the request must be presented before the judicial body by the donor or through communication with the director of the medical centre, describing the personal and familial circumstances of the donor, the purpose of the donation, the medical centre where harvesting is to take place and the identity of the doctor in charge of the transplantation or harvesting, or the person who is delegated for this purpose. The said request or communication must be accompanied by a medical certificate on the mental and physical health of the donor. The appearance before the examining magistrate must be attended by the donor, the doctor who is to carry out the harvesting, the doctor who signed the health certificate and the doctor in charge of the transplantation or their delegate. The person who has to authorise the intervention must also be present. The examining magistrate is to authorise the transfer document if they consider that consent was expressly given freely, consciously and selflessly, and that the other requisites established by the law governing the harvesting and transplantation of organs have also been fulfilled. As demanded by the said legislation, the Voluntary Jurisdiction Law orders that the transfer document describes the possibility of revoking consent at any time prior to the intervention.

Both texts are completely consistent, as they have to be. One of them is for the medical sector and orders how it is to proceed, while the other is for the judge, informing them of the legal procedure to be followed. Giving consent before the legal authority confers a double guarantee on living donor organ donation. On the one hand, consent has to be given before an authority which is both external to and independent of the public health system. On the other hand, the fact that the organ transfer document is issued by a judge adds to security, as this validates the checks on consent undertaken in the medical sector.

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  The safety and well-being of the candidate donor should prevail over the potential benefit for the recipient, so that all of the clinicians who intervene in the study have the ethical duty to protect the best interests of the living donor (Quality of evidence: NG).

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  We recommend that the requisites for acceptance be specified with the donor, together with the information that they would wish to share with the recipient and the procedure in case of unexpected results, whether or not they are relevant for the donation (B).

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  We suggest that the studies of the donor and recipient should be carried out separately, although the teams involved have to be properly coordinated to guarantee good communication, without compromising donor and recipient independence (C).

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  We suggest that professional support and confidentiality be offered when a potential donor decides not to donate and expresses difficulties in communicating this decision to the recipient (NG).

The decision to donate while alive is a voluntary act that potential donors will evaluate finally after they have received complete information. Nevertheless, in the first meeting with the donor, the clinician who commences the study is to accredit their capacity and the reason which has led them to decide to donate one of their kidneys. Although qualified professionals will subsequently report on and accredit their mental state and capacity, the donor should be alone in this interview, in the absence of the recipient and even other family members. The chief benefit which donation will confer on the donor is psychological, based on the personal satisfaction which arises from improving the health of a sick person by means of an altruistic donation. The absence of pressures which mask other motivations should be evaluated at first by means of open questions such as: “Could you let me know your main motivation for becoming a donor?”; “Do you think that if you do not donate, the patient may die due to a lack of alternatives?”; “Do you think that your personal, financial or social situation may have influenced your decision to become a donor?”; “Have you ever felt pressured by anyone to become a donor?”.

In the first meeting the potential donor will be informed of the alternative therapies which are available to the recipient, as well as their survival estimations and waiting times. They will be assured that commencing the study for becoming a donor does not commit them to donating, as they are able to stop the process at any moment without any consequences at all.

In situations when LDKT is considered to be urgent (for example, a highly sensitized patient without vascular access) and study of the donor has to be completed within a short time, the potential donor may be under pressure to a certain degree to donate, thereby invalidating their consent. Due to this, emergency living donation should only be considered in exceptional circumstances, seeking other alternatives using a deceased donor 67.

Sometimes, if risks to the donor's health are increased by the donation, this may be accepted on condition that the consequences for their health are not unacceptable, and if complete and verified information is expressly shown in the consent document. Nevertheless, a conflict may arise between the autonomy of the donor who wishes to donate and the absence of malice of the medical team, which wishes to protect and exclude them. This dilemma may be resolved by reference to the ranking of the principles, in which justice and the absence of malice would be level 1 (the public sphere), while autonomy and beneficence would be level 2 (the private sphere) 61. Public sphere ethical principles affect everybody in the same way, and they take preference over private principles, which everyone manages according to their own ideals and life plan.

Finally, all living donors will be informed at the start of the study that if they find any difficulty in communicating their decision not to donate, they will receive assistance from the transplantation team to do so.

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  We suggest that the clinicians who are in charge of selecting donors minimise sex-based imbalances, ruling out the possible coercion of women to donate (NG).

The professionals who take part in the decisions to select the best of several possible donors should consider the ethical need to minimise any possible sex-based imbalance. Although many studies report that the majority of living renal donors are women, the reasons for this disparity in the donation rates of men and women are still controversial 68. According to the ONT 69 and the Amsterdam Forum 8, 65% of living renal donors are women, while 65% of the recipients were men 8. These differences make it necessary to consider the sex of donors from an ethical standpoint before selecting one. In some circumstances and due to cultural or social pressure, it would seem that women have no other choice but to be selected to donate. If this bias is suspected, the medical professionals and psychologists who evaluate the donor should rule out the existence of possible coercion due to sex.

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  We suggest that precautions be maximized under certain circumstances or when suspicions exist that there may be hidden economic agreements or other spurious benefits, above all in donors who are unrelated (NG).

This evaluation is more complicated in the case of donors who are not genetically or legally related. According to World Health Organization estimations, 8% of the more than 100,000 transplantations performed every year in the world use organs that have been illegally trafficked 70. The Istanbul Declaration defines commercialising organ transplantation as “a practice in which an organ is treated as a basic product, even buying it, selling it or using it to obtain another benefit71. With the exception of Iran, where payment is made and controlled by the state for living donation to unrelated recipients, this practice is universally rejected. Over and above its highly controversial ethical aspects 72, this practice is said to reduce the growth in donations from deceased donors 73. Such agreements are clandestine and are denied in other countries, although subsequent disagreements or failures to fulfil conditions bring to light acts of this type, in which intermediaries exploit the neediest individuals for profit. They also corrupt professionals and clinics in countries with limited resources to investigate and prosecute these illegal practices. Professionals who commence studying a living renal donor have to maximise precautions against certain circumstances which may mask economic agreements or other specious benefits. In the case of donors who are unrelated, unemployed, immigrants or prisoners, the first requirement is to accredit what forms the basis of the relationship of the donor and recipient. The next step is for a multidisciplinary team to help evaluate what motivates the donor, with the aim of reaching a decision. Such vulnerable donors should be considered to be victims, as their decision to donate may be due to coercion, regardless of any promised economic benefit or payment of any other type.

It is a crime to offer or accept an economic reward for donating an organ, and this should be reported if it is suspected. It is also unacceptable in ethical terms when the reward is intangible, as this undermines the principles of dignity, justice and equality. Such practices enable the richest patients to gain solutions for their health problems which are unattainable for ordinary people. Internet has made it easier to buy and sell kidneys from living donors. Although they are banned, it is not hard to find offers or requests for donation in exchange for economic rewards, and the authorities should prosecute these practices. Internet has also enabled the creation of web pages that have the purpose of finding unrelated living donors for direct transplantation. This is ethically inacceptable, unless such donation is anonymous and controlled by medical professionals, as is the case in “Good Samaritan” paired donation programmes with altruistic donors 74. Otherwise we would be turning these websites into what have been called beauty contests, where recipients are evaluated on the basis of their personal appearance and biography, which are irrelevant variables for organ assignation 75.

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  In the case of genetically unrelated donors we suggest that their relationship of kinship or the circumstances which accredit the donor-recipient relationship be documented, to ensure that the donation complies with the law and ethical standards (NG).

Exhaustive knowledge of the identity of the donor and their genetic or legal relationship with the recipient should be the priority in the initial phases of the suitability study. The professionals who take part in the study of the donor (nephrologists, urologists, psychologists/psychiatrists, nurses, social workers and transplantation coordinators, etc.) should investigate the identity of each donor and their relationship with the recipient in depth. To this end they will request all of the documentation which permits accreditation of kinship relationships and, in the case of unrelated donors, the circumstances which verify the intensity and duration of their relationship and its nature, to guarantee that altruism is the main motivation for the donation. The Convention on Human Rights and Biomedicine of the Council of Europe protocol on the Transplantation of Human Organs and Tissues urges protection of the dignity and identity of donors and recipients, guaranteeing individual rights and freedoms without discrimination to attain the maximum professional standards while minimising risks 76.

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  It is obligatory in Spain to maintain anonymity in living donor transplantations involving paired donation and non-directed altruistic donors (NG).

This regulation is not applicable to directed LDKT between individuals related genetically, by legal kinship or close friendship. Anonymity in Spain is obligatory for paired donation LDKT and in non-directed altruistic (Good Samaritan) donations which permit chain transplantations. Nevertheless, not all of the European countries with paired and altruistic donation programmes have legally regulated anonymity 51.

In a study of 414 donors and recipients who took place in non-directed and paired transplantation in Germany and Sweden, where such programmes demand anonymity, 22% of the donors and 31% of the recipients expressed the desire to meet after the transplantation 77. Other similar studies agree that more recipients than donors wish to meet the other party. Although donors and recipients are generally satisfied with anonymity, they consider a strict policy of anonymity to be unnecessary.

Experts in bioethics are divided on this point. Breaking with anonymity may lead to psychological or economic pressures on the beneficiary of the donation, terminating in conflict. Although such situations would be rare, they would cause stress for donors and recipients. As well as being legally obligatory in Spain, keeping anonymity is an ethically acceptable practice, because it encourages altruism and prevents forms of behaviour that could damage social perceptions of donation by living as well as deceased donors.

Occasionally, some donors request to be studied without the recipient knowing. It is not good clinical practice to assume that all recipients will accept related LDKT, although many health professionals or family members believe this. The ethical principle of autonomy for the LDKT recipient may be relevant in specific cases, in which their refusal to receive a certain kidney from a living donor would prevail.

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  The donation of one kidney for transplantation involves accepting a degree of risk for the donor's health that must be minimum, known and accepted by the donor before harvesting (NG).

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  We suggest that the information for the potential donor on the risks and benefits of LDKT be given in at least two phases, and in oral and written format (D).

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  All donors are recommended to undergo a lifelong medical follow-up (B).

From an ethical viewpoint the professionals who assess donors must not forget that they have to work in favour of the donors’ interests. Nephrectomy of a kidney for transplantation and the consequences of this for the donor will never be free of possible complications, and some may consider this risk to be ethically unacceptable. However, in LDKT it is accepted that to attain the benefit of the transplant it is possible to accept a minimum or reasonable level of risk for the donor. Due to this, all living renal donors must receive precise information as many times as is necessary about the risks of major surgery and the restrictions or precautions that are involved in living with a single kidney 79. We suggest that this information be offered in at least two phases, in oral and written format 80. The general risks shared by all living renal donors will be described in the first phase, and in the second phase, after the results of the tests on the donor's state of health have been received, the specific risks for the donor must be described (CRD, hypertension, diabetes mellitus, preeclampsia, etc.). These risks are covered in other chapters of this Guide. Tools such as the ESRD Risk Tool for Kidney Donor Candidates” may aid objective work when evaluating each one of these risks 81.

Additionally, donors must accept undergoing regular check-ups after nephrectomy to permit the early detection of cardiovascular and renal risk factors, among others, which can be controlled by changes in lifestyle, dietary recommendations, pharmacological therapies or surgical procedures. The data on living renal donors lost to follow-up in Spain (2010-2017) are 18% and 13% in the fourth and sixth years, respectively 69; some studies in other countries detect far higher percentages 82.

Post-donation follow-up for living renal donors is also an ethical obligation to protect their health. It is an indispensable tool which uses the best scientific methodology to verify the risks of donation at different times, with the smallest possible distortions 83. Living renal donor follow-up registries are included in a directive of the European Parliament 84 as well as in our regulations.

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  Donors with a genetic or emotional tie who do not live in the same country as the recipient are especially vulnerable, so that extraordinary vigilance is needed to ensure their protection and care after donation (NG).

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  We suggest that donation by non-resident donors should not be accepted when no long-term medical follow-up can be guaranteed for them (NG).

The Committee of Ministers of the Council of Europe is aware that many countries accept donations from non-resident living donors with or without a genetic, legal or emotional tie with the recipient and who arrive in the country legally (with a visa or other authorization) and who wish to donate. It therefore adopted a resolution in 2017 for the selection, assessment, donation and follow-up of non-resident living donors, as it recognized that such individuals are especially vulnerable, so that they require extraordinary vigilance to ensure their protection and care after donating 85.

It is important to maintain close vigilance to ensure the early detection of possible cases of human trafficking for the purpose of organ harvesting for transplantation. This question may be particularly difficult to detect when assessing and accepting a non-resident living donor.

- Recipient and living donor who live outside Spain. Before they travel to Spain the hospital where the transplantation is to take place should receive a detailed report which accredits the recipient and possible donor as suitable for transplantation and donation, respectively, according to Amsterdam Forum criteria for living donation. The recipient is to supply clear proof of genetic or legal kinship. In exceptional cases it will be possible to accept another type of emotional tie if this is accredited with absolute certainty within the legal framework in force in Spain. If a visa is required for entry into the country this must have a duration of at least six months. The medical reports on suitability, informed consent, approval by the Ethics Committee and the legal appearance are to be prepared according to the legal requisites, and a translation is to be supplied when applicable. The recipient will have no access to deceased donor KT in Spain. The expenses deriving from the procedure are payable by the recipient or secondarily by their country of origin.

- Recipient resident in Spain and a non-resident living donor. All of the above safeguards will be applied regarding the medical report on the donor, which must be prepared in the donor's own country. In the specific case of living donor transplantation, the transplant will be linked to the care associated with the donation process, as well as any possible complications of the same 86. This will therefore be applied to donors without social security or recipients who are covered by other regimes such as MUFACE.

Centres which are authorized for LDKT must have a specific protocol for acceptance of the recipient of an organ from a non-resident living donor. They should previously inform the ONT through the autonomous community coordination system of the dates on which the surgical operations are to take place, and comply with the protocol according to the document “Living donor KT in non-resident recipients” 85,87.

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  We recommend that the IC document should include the risks which are common to all donors, the particular risks for the donor in question and that it be signed by the latter without the presence of the recipient, family members or persons who could influence their decision (B).

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  Open questions are to be used in the signing of the IC document to confirm that the donor has understood the information on nephrectomy and its risks, and that their decision to donate is firm and without duress (NG).

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  Donors are to be informed of their right to leave the study at any time, as well as the procedure to be followed if after the removal of a kidney it were not possible to engraft it in the recipient (NG).

The instructions in this step must be followed exactly. The wording of the IC document varies widely from one hospital to another. Now may be the time to standardise a specific national informed consent document that includes the peculiarities associated with nephrectomy for LDKT. A copy of this must be given to the donor and recipient. This initiative agrees with the opinions of professionals involved in transplantation in transplanting hospitals in Spain and other European countries 47.

The act of signing the informed consent document (IC) is considered optimum when it takes place in the presence of professionals who have taken part in the study of the donor and a surgeon who is a member of the donation or transplantation team. In this session all of the analytical and radiological tests will be discussed, together with reports by other specialities and any other result which may affect the donor's safety or the success of the transplantation. Now will be the time to offer all of the additional explanations that the donor may require. Before signing, the medical team will use open questions to confirm that the donor has comprehended the information, is aware of the nephrectomy process and its intrinsic risks, and that their decision is firm and was made without any duress whatsoever. The donor will also be informed that they are free at any time to revoke their consent, and it is therefore advisable for the recipient to be absent during this step.

The IC document for the donor is to include at least the following:

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  The risks of the surgical procedure (type of surgery, anaesthesia, transfusions, infections, further surgery, mortality).

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  The risks deriving from the nephrectomy such as the possibility of CRD, hypertension or cardiac pathology.

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  The individualized risks for the donor studied, due to borderline analytical results, pre-existing disease or family history. In young women with the potential to become pregnant, risks of gestational hypertension or preeclampsia will be reported.

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  Actions in case the collected kidney cannot be engrafted in the recipient. The donor must decide at the moment of signing the IC if the kidney should be transplanted to another person or re-engrafted in the donor.

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  The right to withdraw their IC at any time prior to surgery.

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  Quantification of the risk or possibility that the kidney will not function in the recipient or that it will cease working prematurely.

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  Commitment to medical follow-up after donation.

The IC document for the recipient is to include at least the following:

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  The risks of the surgical procedure (anaesthesia, transfusions, infections, further surgery, mortality).

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  The risks that the transplanted kidney will not function (thrombosis, rejection) or will cease to work prematurely.

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  The adverse effects of immunosuppressant medication.

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  The risks of catching diseases that were not detected in the donor due to the window period or the impossibility of diagnosis.

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  The recurrence of the original renal disease.

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  The function of the Healthcare Ethics Committee is to protect the rights of donors and, in the case of conflict, to help decision-making (NG).

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  We suggest that the medical reports arising from the study of the donor and recipient be sent to the Healthcare Ethics Committee, as well as all of the information which is considered to be relevant for risks and motivation analysis (C).

RD 1723/2012 covers intervention by the Healthcare Ethics Committee in the evaluation of a living donor: “In any case, before proceeding to obtain the organ, it will be necessary to have a report by the corresponding Ethics Committee”. To this end the professionals who have studied the donor and recipient will send a request to the Healthcare Ethics Committee for its report, accompanied by the clinical reports on the donor and recipient which contain a detailed clinical history and the tests used to assess their state of health. These will be accompanied by the donor's mental health report and the informed consent documents of the donor and recipient. The Healthcare Ethics Committee has the function of protecting the rights of donors and, in case of conflict, to help decision-making. Its mission is not to evaluate the suitability of the procedure, but rather to ensure that the donor is properly informed of the probabilities of success and the risks which they accept. In some cases they may request an interview with the donor to confirm the degree to which they are informed and the absence of coercion.

The Healthcare Ethics Committee will issue a document on the suitability of the living donation, or it may request an additional report or consideration in connection with the guarantees for the donor. This report will never substitute the responsibility of those who control the process of living donation and transplantation.

In North American hospitals LDKT programmes have been introduced recently which include the so-called “independent living donor advocate”. This individual is independent of the transplantation team and is not involved in the study of the donor and recipient. Their mission is to ensure that the donor and recipient have all of the relevant information about the donation process and that they have understood it properly, ruling out the possibility of coercion or commercialization as far as possible and defending the donor's rights 88. One hospital in our country which is very active in LDKT has an independent professional who is unconnected with the transplantation team, who accredits the correctness of the whole process prior to the LDKT procedure. Nevertheless, for the majority of hospitals the authors consider that the Healthcare Ethics Committee included in Spanish law perfectly fulfil the role of this independent advocate and that therefore there would be no need to involve other professionals for the same purpose.

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  Selection of the type of renal replacement therapy is a shared decision-making process by the patient and the medical team (Quality of evidence: NG)

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  All patients who are considered candidates for receiving a KT should be offered the possibility of receiving a kidney from a living donor (NG).

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  All patients who are considered candidates for receiving a KT should be informed that the best option is transplantation before they need treatment by dialysis (NG).

The decision-making process for the type of renal replacement therapy (RRT) to be used is completely covered by the concept of shared decisions, with at least two parties: the patient and the medical team of clinicians, the nephrologist and a nephrology nurse. The clinicians will supply scientific evidence on the diagnosis, aetiology, prognosis and different therapeutic options, including conservative treatment without dialysis or a KT. The patient will describe their values, their social, family and economic circumstances and their worries and preferences. Both parties will eventually reach an agreement on the best options to be selected.

This selection of a RRT, within the context of an unstoppable flow of information associated with the increasingly explicit right of patients to independently decide on every aspect that affects their health, implies the complete abandonment of the classical paternalistic model. In this new deliberative model the patient decides, while medical professionals pay respectful sensitive attention to their individual preferences, needs and values, before agreeing to the decision of the true protagonist in this process. When choosing a RRT this deliberative model is far more suitable than the purely technical and informative alternative, in which the clinician simply functions as an advisor. In the deliberative model which this Guide proposes, the patient enters a trusting relationship with the clinician and nurses that is based on this active two-way exchange of information, to reach the best shared decision. The clinician guarantees that the information is appropriate, comprehensible and easy to access, especially the information about therapies and their advantages and risks.

The best shared decisions are those which have a sufficiently scientific basis for their efficacy and safety, while being as suitable as possible for the values, preferences and aims of the patient. The tools which can aid this decision-making are instruments that help the patient to obtain information and answers to their key questions about what they should do or what they have to know to reach a decision. These tools can come in a wide range of formats: pamphlets, information sheets, videos, on-line applications or interactive websites, etc. The information supplied should be expressed appropriately and effectively, high quality and in an easy-to-understand clear format 90,91.

When a patient reaches stage 4 CRD, with an estimated glomerular filtration rate (eGFR) below 30ml/min, the first step should be their assessment as a possible candidate for LDKT 92. Parallel to this option, it is also necessary to select one form of dialysis or the other (peritoneal or haemodialysis), in case it is impossible to carry out transplantation before dialysis is required. The ideal context for this process of information and selection of RRT type is during consultation for ESRD, where apart from this process a series of increasingly standardized activities are also implemented, in a way that could be formally accredited (Table 1).

The webpage set up by the Departament de Salut of the Generalitat de Catalunya contains a detailed set of tools for use in a joint decision for the treatment of ESRD 91 (Table 2). Whether online or personally, the different options have to be compared, and it would be advisable to detect patients’ preferences by means of a test. This space would allow patients to reflect and use the results in conversation with their clinician.

Shared decision-making ensures that patients know more and are better informed, with greater awareness of their own values and better able to perceive risks and advantages: they are able to decide without negatively affecting their health 93.

There is currently debate about the relevance of using quantitative methods to select the type of RRT to be used, to calculate the risk of mortality or the probability of survival. Calculators of this type are widely used in the Anglo-Saxon world, while they are used less often in Spain. One of the best is iChoose Kidney, which was developed in the Emory (Atlanta, U.S.A.) transplantation programme 94. This calculator was found to be useful in a randomized trial 95, and it was validated in Ontario, Canada 96. It includes age, sex, race, time in dialysis and the most important comorbidities. The Canadian validation of this calculator, which included 0,520 patients in dialysis and 4,505 transplanted patients, was able to predict mortality at 3 years. An example shown in the publication 96, is that a 70 year-old women of African American, with more than one year in dialysis, hypertensive and diabetic, has a risk of mortality at 3 years of 27% in dialysis and 11% if she receives a transplant. If the kidney comes from a living donor the risk is 6%, and if the donor is deceased it stands at 12%.

Apart from the different strategies developed by each hospital or ESRD unit to properly process the shared decision on the type of RRT to be used, other specific strategies have been developed to help the specific decision involved in LDKT (Table 3) 97. The materials which aid the decision (booklets, videos, online material, text messages and calculators, etc.) centre on general education about the process involved in renal disease and transplantation. They are more or less adapted to patients in general or culturally sensitive aspects, and they are aimed at potential donors as well as potential recipients. The strategy in which each unit prepares its own materials is more widespread in Spain, essentially pamphlets or small explanatory books which in a series of chapters explain different aspects associated with the process of donation, describing advantages and drawbacks, risks for the donor and recipient, and the results that can be expected. The questions which any material for potential renal donors should answer are shown in Table 4. Booklets can never completely replace a conversation which lasts for as long as a potential donor may require, in which they are able to raise any questions 98.

All CRD patients should be considered and assessed for KT, except for those with an absolute contraindication, because KT offers a higher quality and longer life than dialysis 3,4. Patients who receive an early KT from a living or deceased donor have better personal and graft survival than is the case for those who had already started dialysis 99. Thus an early KT should be offered to all of the patients who have the possibility of a living renal donor. Patients and their family will be informed of this option in the decision-making process in cases of ESRD, and they will be given informative booklets and referred for a first pre-transplantation consultation.

The European guides recommend that patients with gradual deterioration of renal function and an eGFR <15ml/min/1.73 m2 should be assessed for inclusion in the waiting list for a preventive or early KT 3,4. The patients who are considered to be potential candidates for KT will be referred to start assessment when their GFR is <20ml/min, once the possibility of a living donor KT has been examined.

• •

  The information given to the donor will be standardized and will include details about the assessment process and acceptance; the risks, benefits and evolution that can be expected in the donor's health; alternative therapies for the recipient; how personal health data are used and donor support personnel (NG).

KT programmes should develop the process by which candidate donors are informed 100. The use of standardized checklists has been suggested, to ensure that all of the relevant information is supplied 101. In the United States, the Organ Procurement and Transplantation Network has developed a list to ensure the suitability of the process 102, as well as a document for potential donors in language that is easy to understand 103.

This information should be communicated in each KT scheme in the most favourable environment in each case; the most frequent and appropriate circumstances for this are consultation in the case of ESRD, consultation before transplantation or transplantation coordination, where patients are referred after a general visit to nephrology or dialysis units. It often happens that the possibility of living donation is raised in the context of the selection of a RRT in a nephrology consultation. This leads to a specific visit and analysis of this type of transplant with specialized nephrologists. It is therefore essential that the nephrologists who are in charge of CRD patients always keep in mind the possibility of treating them with the best available therapy, which is living donor KT, if possible prior to the need for dialysis. The best time to present this possibility and check whether potential donors are available is when the potential recipient is in stage 4 CRD, with an eGFR of from 16ml/min to 30ml/min.

A range of printed material may be used to offer this information systematically, facilitating the presentation and discussion of the basic concepts with the patient or potential donors. From the first, potential donors should receive clear information on the details of the assessment process. The language used has to aid communication and the mutual understanding of a potential candidate and the clinicians 104,105. The climate in which this exchange takes place should permit questions of all types, adapting to the particularities of the candidate 105,106.

The information which has to be supplied is included in many guides and declarations 1,2,104,107,108. Some regulations stipulate a minimum content that should be present in the informed consent process 107. Table 5 shows the information that should be supplied to the potential donor.

The most common worry expressed by renal donors prior to donating is the possibility of suffering renal failure themselves in the future, together with the recovery process, its duration and possible complications 100,109,110.

Potential renal donors have to know that they will only be able to donate once in their life, and they should also be aware of the alternative renal replacement therapies available to any potential recipient. When incompatibility due to blood group or HLA sensitization is detected, the donor should be informed of the range of options that may be available, such as ABO-incompatible KT, paired KT 111–113 or HLA desensitization, which in general usually require a specific informed consent.

The assessment process for a potential renal donor involves the risk of discovering previously hidden pathologies and diseases, and these may even require diagnosis and therapy. All findings and the decision about what to do should be shared with the individual who has now ceased to be a renal donor candidate and is now a patient. One such finding may be that a previously accepted family relationship (such as paternity) is ruled out, or that a new previously unknown relationship is discovered 78. There is no agreement on the appropriate behaviour in these cases. At an early stage it is advisable to warn that such a discovery may occur. The KT scheme should establish an information protocol for such cases, regarding when and how to inform the interested parties 78,114–117.

Renal donor candidates should receive information on the surgical, medical and psychosocial risks involved (sections 5-7 and 17), including the necessary individualization and the inevitable degree of uncertainty and lack of evidence in the majority of cases. For example, the risk of mortality 3 months after donating is estimated to stand at 0.03%, and no profile has been established of donors who are at increased risk 118–120.

The surgeon who carries out nephrectomy on a renal donor has a particular responsibility to ensure that they understand the potential short and long-term risks. The surgeon is usually a urologist in Spain, and they will have their own process for informing the donor, centring on the nephrectomy itself, which is usually performed laparoscopically. The urologist will explain the purpose of the surgery and describe the technique they will use and the risks associated with it, obtaining the donor's informed consent. On the other hand, potential donors should also receive information on the circumstances that may arise while they live with a single kidney. These will include exceptional risks such as severe injuries or medical problems involving lithiasis or infections that may compromise the working of their remaining kidney. It can be confirmed that over the long-term there is no significant tendency for GFR to gradually decrease in any age group 121, and that the incidence of hypertension does not increase over time 122.

A question that young women who are potential donors ask is about the possibility of gestation. An increase in gestational hypertension and preeclampsia has been described in renal donors in comparison with their general non-donor health control group. Nevertheless, these findings are not associated with any extra complications for the mother or foetus 123. Special attention should be paid to checks of arterial pressure, weight gain and proteinuria, although these are generally the same as those recommended for all pregnant women 124.

Although it may be advisable to use transparent quantitative tools in the process of informing potential donors about the long-terms risks involved 125, calculations of this type are highly limited and we have no exact means of estimating the risk that could be attributed to renal donation. Even though no official regulation exists on this point, potential donors should be told that in the unlikely event of their developing ESRD, they would be given maximum priority to receive a kidney transplantation 126,127.

With the same degree of emphasis that is used to inform them of the risks involved, the transplant scheme should inform renal donation candidates of the potential benefits of their donation. The difficulty of measuring this benefit is not very different from the above-mentioned difficulty of measuring the risk 128.

The donor should be informed about the estimated survival of the kidney as well as the recipient at 1, 5 and 10 years, after LDKT as well as a deceased donor KT or treatment using different dialysis techniques. This information should preferentially be based on the results of the renal donation scheme in question. Although in the U.S.A. potential donors should be told about the survival of the kidney and recipient one year after KT 107, there is no such obligation in Spain.

Donor candidates should know that the potential recipient will not be informed of any aspect of their health without their express consent 129,130. Equally, the donor will not be informed of anything about the recipient without the consent of the latter 2,107. The potential donor should also know the economic and social implications of their donation, the impact that it may have on their professional performance and the length of time they will be temporarily off work, under normal circumstances as well as in case of complications. On the other hand, the donor should also be told that it is illegal to obtain any material benefit (economic or any other type) as a reward for the donation.

The informing clinician should tell the renal donor that they are able to decide not to donate at any time during the process, and that regardless of the reason for this, they will continue to have the full support of the transplantation scheme. On the other hand, the majority of programmes reserve the right to accept or refuse a potential renal donor, so that the latter should be informed of this in detail, together with the reason for the decision 131. In general, it is assumed that a transplantation scheme which rejects a donor due to unacceptable risk for their or the recipient's health should seek a second opinion from another scheme if the potential donor requests this.

The renal donor should be informed of the risks and benefits which the recipient of the kidney will experience, including among others: 1) that the therapy is not definitive, and that gradual loss of renal function over the years often occurs, due above all to the development of chronic forms of rejection, 2) that there is a possibility of around 5% that the graft will be lost at an early stage because of acute rejection, primary failure of the graft, thrombosis or infectious complications. This aspect is covered in greater detail in Table 689.

The essential point of the process is to hold a suitable interview in a completely trusting and frank atmosphere, without the potential recipient or any of their family being present. A persistent doubt or ambivalence will normally lead to a refusal to donate, and in this case as well as in that of a clear negation, the scheme should respectfully and confidentially support the decision and the individual who had been a potential donor and finally decided not to proceed 132. Although it often used to be employed in the past, it is unadvisable to use a “medical alibi”, or justification of the decision not to donate for the potential recipient by giving a false medical reason to justify the choice. It would seem to be better to state that “this donor is unsuitable” in general, without giving a false reason 133. The transplantation scheme should help the donor to communicate this if they wish. On the other hand, in some cases the potential recipient will not accept a voluntary renal donation, and in this context conflict reduction procedures should also be in place, permitting a refusal without any other consequences.

• •

  The process of studying a potential renal donor permits a very wide range of approaches which depend on the donor's characteristics, the urgency of the study and local facilities and waiting times for examinations (NG).

• •

  The first step consists of the screening of a potential renal donor to rule out unviable cases with a minimum of inconvenience for the donor and resource consumption. This screening should therefore include: a review of the pre-transplantation study of the recipient, donor-recipient compatibility (ABO group, crossmatch test) and evaluation of the potential donor, with basic analysis and estimation of their GFR rate (NG).

The process of studying a potential renal donor permits a very wide range of approaches which depend on the donor's characteristics, the urgency of the study and local facilities and waiting times for examinations. Studies may take place simultaneously from the first in very clear cases, above all if the aim is to reach a swift conclusion. The order in which examinations take place should also be varied depending on the case; for example, in donors with specific pathologies that require approval by other specialists, no in-depth studies should be undertaken until their approval has been obtained.

The first step has to consist of the screening of a potential renal donor within the context of the initial consideration of the donor-recipient pair, using hardly invasive and immediate basic examination techniques that will make it possible to decide whether the donation is possible. The aim here is to rule out unviable cases with minimum inconvenience for the donor and resource consumption. This also gives the donor time to confirm their decision. No written informed consent is required for this first step, simply the verbal acceptance of the potential donor. Written consent will be required later, when invasive examinations take place, as well as the final consent to nephrectomy.

This first screening should include three fundamental aspects:

• 1)

  Review of the pre-transplantation study of the recipient: confirm the indication for transplantation, that the pre-transplantation study is appropriate and complete, and assessment of the risk and prognosis.

• 2)

  Donor-recipient compatibility: determination or repetition of the ABO group in blood bank, donor HLA typing (and of the recipient, if they are not included in the deceased donor list) and the first crossmatch test. This makes it possible to consider the possibility of directed transplant if there is ABO compatibility and a negative crossmatch test; otherwise, it makes it possible to offer the option of a paired KT or a desensitization procedure.

• 3)

  Assessment of the potential donor, with anamnesis and physical examination, basic analysis with serum creatinine and eGFR, glycaemia, liver function, haemogram, haemostasis, HBV, HCV and HIV serologies and microalbuminuria/creatinine and sporadic sediment in urine.

• •

  Informing society about living donor transplantation should stimulate promotion of the same (NG).

• •

  Attending to the media and proactive information should be priorities (NG).

The scientific evidence in favour of LDKT, especially when it takes place before the need for dialysis, should stimulate its promotion in educational spaces for all types of healthcare professionals, including those who work in primary care 134. On the other hand, dialysis therapy providers should be fully aware of the advantages of transplantation, especially from a living donor, so that they will be able to educate the patients they treat regarding this.

Agreements should be reached at all levels of society, the media and even religious organizations to promote and drive LDKT. Technological advances should therefore be used to spread a wide range of educational and training tools throughout society. This educational work should be even more intense where there is a low educational level in different communities and regions, to overcome economic and social concerns.

Attending to the media has always been a priority for the ONT, as it is for regional and hospital transplantation coordinators. They are all aware that information given to the media will directly affect the whole of society. All medical professionals involved in the donation and transplantation of organs should cooperate all of the time with the media, always being available to answer their requests and questions, while attempting to quell the possible negative effects of a poorly expressed news item as quickly as possible. Medical professionals should maintain what is known in communication theory as “proactive communication”. Journalists welcome this attitude, and it leads to personalized daily attention. The continuous publication of positive news has helped to create the good image enjoyed by transplantation in our country, where it is considered to be not only normal, but also and above all a basic service of our healthcare system. In the social imagination transplantation is associated by Spanish citizens with life, and this perception surely aids the donation of organs in general, and donation by living individuals in particular. Basic communication principles such as the need to use clear, concise and well-argued messages, coherent arguments, properly explained complexities, the tone of messages and of course the most suitable techniques to express them are of key importance for the system to work.

As the ex-director of the ONT, Rafael Matesanz, writes: “You should always attend to journalists when they call, in the best possible way and regardless of where they are calling from. And you have to do so as quickly as possible, because journalists usually don’t have the luxury of being able to wait. That way we will be able to prevent lots of misunderstandings that may end up as malicious rumours, while on the other hand we’ll have the opportunity of spreading a positive image of the process.” 135

• •

  Extracting a kidney for donation should be included as a specific cause which justifies the declaration of temporary incapacity to work, with the resulting financial support from the social security system (NG).

• •

  The direct accredited costs incurred by a donor due to donation should be repayable, and their medical care should be guaranteed for life (NG).

• •

  The change in the health circumstances of an individual because they have donated cannot give rise to penalizations in contracting or renewing insurance policies or loans of any type (NG).

Kidney donation leads to problems at work in a certain number of cases. Donors have to miss a lot of workdays due to medical tests and the postoperative period. It is possible that they may even lose their job due to the consideration that interventions of this type are “voluntary”. Restrictive interpretation of the General Social Security Law (art. 128) prevents recognition of temporary incapacity to work with the right to economic support, as the donor is considered to be neither sick nor to have suffered an industrial accident. Many donors therefore take a holiday or unpaid leave during the donation process.

This lack of work-related protection for living donors has to be resolved, and the harvesting of an organ for donation should be included as a specific cause which justifies the declaration of temporary incapacity to work and the resulting economic support from the social security system during the harvesting and subsequent recovery of the donor, including the impossibility of dismissing the individual during the donation process. Although the current regulation governing temporary incapacity already permits this form of interpretation, it would be advisable for Spanish law to include this explicitly.

A more ambitious and encouraging initiative could take the form of social and work-related protection similar to the current system for pregnancy and birth, with a similar amount of leave to that granted to parents. This measure would affect about 400 people per year, a very low figure. Resolving this problem would encourage people to donate kidneys while alive. The direct and accredited costs incurred by donors due to their donation should be repaid, and they should be guaranteed life-long healthcare. Nevertheless, no economic reward can be set, as this is prohibited by current law.

The change in their health circumstances which someone may undergo due to having donated a kidney should not lead to penalties when they take out or renew an insurance policy or any type of loan. 136.

Although it is not the same in all hospitals, the majority recommend a study protocol similar to the one shown below 9,101,137,138:

• •

  We recommend that the initial study should include the estimation of GFR using validated formulas (Quality of evidence: B).

• •

  We recommend that the measurement of glomerular filtration should be confirmed by means of more precise exogenous markers, such as 125- iothalamate, 51 Cr-EDTA, iohexol or Tc-DTPA, especially in patients with borderline renal function (B).

• •

  Study using 99Tc DTPA is suggested when there is a size difference between both kidneys greater than 10% (C).

• •

  The donor GFR measured before donation should be sufficient so that afterwards the foreseeable GFR will remain within values that are acceptable for their age and sex during the rest of their life (B).

• •

  We suggest that the decision to accept a candidate with renal function below the required threshold or who has additional risk factors for progression to chronic renal failure should be made on an individual basis (D).

• •

  We suggest that the donor be informed and that the informed consent document should contain a statement of the slight increase in the risk of suffering chronic renal failure during their lifetime (D).

• •

  We recommend that all donors should be followed up for life, with especial attention to renal function, proteinuria and arterial blood pressure (B).

• •

  We recommend that a detailed clinical history should be prepared for all potential KT recipients, with especially detailed content on any family history of renal disease. It is indispensable to exclude hereditary renal disease from potential donors (A).

All potential KT recipients should have a detailed history of renal disease in their family and, when possible, the diagnoses of the same. This will help to detect familial risks in potential living donors. At the same time, all donors should be questioned about their personal or family history of hereditary diseases. If the disease of the recipient is due to a hereditary renal disease, it is indispensable to rule this out in the donor, using radiological examinations, renal biopsy or genetic studies if they are necessary 9,137,138. Autosomal dominant polycystic renal disease stands out among the most important diseases. Classically certain criteria were used to diagnose this and differentiate it from simple isolated cysts 153. In case of doubt a genetic diagnosis will help us to be sure that the donor will not suffer the disease in the future 154. Other hereditary diseases or ones with a familial component that should be ruled out in donors are Alport's syndrome, thin basement membrane disease, glomerular pathologies with increased familial involvement (IgA, membranous, focal and segmentary, membranoproliferative), LES and atypical haemolytic - uremic syndrome. Potential donors who are carriers of the same disease as the recipient must not be accepted as donors.

• •

  Tests to detect transmissible infections should be applied to all potential living donors (B).

• •

  We recommend that if a potentially transmissible infectious disease is found, the medical team and recipient should accept or reject the suitability of the donation after receiving detailed information about the risks that would be involved (B).

• •

  Positivity for HIV or HTLV (humanT lymphotropic virus) is considered to be an absolute contraindication against living donation (B).

• •

  We recommend that the donor and recipient be informed of the risk of post-transplant primo infection in the case of a CMV+ donor and CMV- recipient, and the risk of lymphoproliferative disease in the case of an EBV+ donor and EBV- recipient (B).

The tests to detect transmissible infections which should be applied to all living donors were described above 156,157. We recommend that these tests should be applied shortly before the transplant for the highest risk diseases, so that window periods can be ruled out. Especially for HIV, HBV and HCV it is preferable that the relevant tests be applied in the month before donation 9. Some active or latent infections will not be a contraindication if it is possible to treat the donor for them effectively. It is important to undertake a correct anamnesis of the risk factors for latent diseases in the donor, with special emphasis on factors involving their social behaviour, addictions, professional risks, geographical risks or exposure to animals. The criteria for accepting transmissible diseases in the donor vary from country to country 26,27 and they have changed rapidly over recent years. When the donor has a potentially transmissible disease, the fully informed medical team and recipient will reach a decision on whether it is possible to accept the risks of transmission 9,137.

• •

  An exhaustive study of the donor is recommended if they have anaemia (A).

Many hospitals already systematically perform hypercoagulability studies of all donors. In spite of this, such studies are considered to be obligatory only if there is a history of thrombosis. A previous incident of pulmonary thromboembolism or deep vein thrombosis may constitute a contraindication against donation (NG). In women who are carriers of V-Leiden factor the preoperative suspension of contraceptives or hormone replacement therapy would be indicated.

In the case of anaemia an exhaustive study prior to donation is indispensable 137. This is also the case when a haemoglobinopathy is detected.

• •

  We suggest that psychological assessment should be based on a clinical interview and psychometric evaluation (Quality of evidence: C).

• •

  We suggest that psychological assessment should be undertaken by psychologists or psychiatrists with clinical experience and who do not take part in care of the recipient (NG).

• •

  We suggest that the contents of the psychological assessment protocol should be uniform, regardless of donor type (NG).

• •

  We suggest that psychologists should be included in the multidisciplinary transplantation teams (NG).

Psychological assessment should include mental health evaluation of the donor, as well as their comprehension of the risks and circumstances of donation. The relationship between the potential donor and patient should be analysed, together with the motivation to donate and coping strategies for surgery and possible complications, among other factors 174–178. A wide range of methods and criteria exist for psychological assessment; in some cases formal criteria are used, while others use semi-structured clinical interviews 173,179,180. We therefore suggest that an interview and psychometric evaluation should be used, so that sufficient data are available for the generation of a final report. Psychosocial assessment should be performed by psychologists or psychiatrists with clinical experience and suitable qualifications, as well as mental health expertise. We also recommend that they should not take part in care of the recipient, to reduce conflicts of interest in their assessment of the donor candidate. Psychosocial assessment should take place in the absence of the recipient, family members or any other individuals who may influence the donor's decision, regardless of their type of relationship with the recipient.

• •

  We recommend not to proceed with the living donation process in case of severe clinical or personality disorders, as well as acute phase disorders and situations of stress, vulnerability, personal defencelessness or serious addictive disorders (B).

• •

  We recommend contraindicating donation in altruistic or Good Samaritan candidate donors if they have a notable or exaggerated predisposition to arouse the admiration of others or be the centre of attention (B).

In general, the main psychosocial contraindications for living donation would include severe psychiatric problems or substance abuse, the presence of major financial stresses that may have a coercive effect on the decision to donate, or which may worsen significantly as a result of donation, and any medical complication, evidence that the potential donor has experienced pressure or the undue pressure of other individuals to donate, restricted understanding or capacity to understand the risks and benefits for the renal donor or transplant candidate, or ambivalence about whether to proceed with the donation 172,181.

The following contraindications should also be taken into account for good Samaritan donors candidates: a) An unrealistic opinion that transplantation involves no risk of rejection or failures; b) Donor confusion about who is responsible in case of transplantation failure; c) Seeking monetary reward; d) Desire for media attention; e) Use of donation as a palliative for a psychological problem or another underlying disease; f) Donor willingness to decide on the type of recipient (regarding gender, age, race or ethnic group, and g) Desire to meet the recipient and become involved in their life 182.

• •

  We suggest that the psychological interview should elicit motivation and post-donation expectations, sociodemographic aspects and background. It should include cognitive evaluation, emotional evaluation and the evaluation of coping strategies, resilience and available emotional support (NG).

• •

  We recommend that altruistic or Good Samaritan donors should be subjected to a more exhaustive evaluation, with a careful assessment of their motivation as the most important criterion (B).

In the psychological interview with a potential donor all of the areas that could compromise the intervention in some way should be taken into account. These include not only the medical area, but also social, economic and professional, emotional, cognitive and familial factors. It is essential to ensure that the donor is aware of possible negative effects that may arise due to the donation 174,175. At the start of the interview it is advisable to check the knowledge of the donor about donation, in order to give comprehensive additional information about the procedure, possible risks, benefits, results and post-donation follow-up, etc. During the assessment some additional aspects should be assessed, such as that the donation is selfless and seeks no economic interest, publicity or any type of personal promotion in all cases, and most especially for Good Samaritan donors. This latter type of donation is anonymous in Spain by national law 172. The interview should cover a list of subjects including mental health history, drug abuse, that the donor is able to understand the risks, social support, motivation and voluntary nature and the donor recipient relationship, etc. 183. During the initial phase of the interview factors in connection with the information held by the donor about the procedure, risks and possible complications will be explored. In connection with post-intervention expectations, it is necessary to verify whether the donor has taken into account that, although rare, they may suffer renal complications that may threaten their health to the extent that they need renal replacement therapy. All of the above points will give us information about the motivation which leads to donation, and this is especially important for Good Samaritan donations.

The interview will focus on the sociodemographic data that are necessary for all psychological assessments and especially those which are relevant for organ donation, such as healthy habits and possible substance consumption.

The cognitive assessment will evaluate the intellectual capacity and maturity of the donor to ensure that they understand the significance and possible consequences of their actions. The aim here is to maximise precautions to ensure that the process of giving consent is free, without any family, professional or economic pressures 184.

The emotional assessment will explore the possible existence of emotional disorders which affect their free decision to donate, such as anxiety, depressive or impulse control disorders, etc. This assessment will be confirmed in the psychometric evaluation. Whether the decision is a mature one and the result of proper reflection will also be taken into account, or whether on the contrary it was due to a thoughtless act that may have been the consequence of a momentary impulsive action. Lastly the normal coping strategies used by the donor will be taken into account, as these may be predictors of good post-intervention well-being. The capacity of the donor to practically resolve problems will therefore be explored, together with their capacity to control their emotions and manage stressful situations, taking into account the fact that donating an organ is intrinsically stressful. Adaptive coping strategies such as active confrontation, planning, impulse control, positive reinterpretation and the search for social support may all be considered. On the contrary, negation, avoiding concentrating on their own negative emotions and addictive forms of behaviour would all be considered strategies that fail to adapt, and they would therefore be predictors of poorer post-intervention welfare 185.

• •

  We suggest that psychometric assessment based on the use of an objective test should be used, making it possible to evaluate clinical personality traits (C).

• •

  We suggest that the Millon MCMI Questionnaire (which is now in its IV edition) should be used for psychometric assessment (NG).

• •

  We suggest that the evaluator should be familiar with this test and have sufficient experience in applying it (NG).

Aside from the results of the interview, it is always advisable not to reach a diagnosis or take important decisions for patients without the support of objective data which complement clinical judgement or diagnostic impression 186.

We propose using the Millon MCMI Questionnaire for this purpose, because it is able to identify the presence of severe clinical syndromes such as clinical personality traits and severe personality pathologies. It supplies information and a nomenclature which better fit ICD and DSM diagnostic criteria, as medical personnel in general are more used to these ones 187,188. This questionnaire offers a dimensional vision of the normal-abnormality continuum in psychopathology, making it especially interesting for the evaluation of a collective (consisting of potential donors) who in principle are not considered to have any psychological pathologies at all 189–190, and it has been used to evaluate living renal donors 191,192.

• •

  We suggest that living donors should be followed up psychologically using interviews, especially those in whom pathological personality traits had been detected (NG).

• •

  We suggest that recipients should be followed up psychologically to improve the survival of the organ and patient (NG).

In the same way that follow-up of living donors is recommended over the short, medium and long-term to prevent or treat risk factors that could compromise their health in general and their renal function in particular 193, follow-up of the recipient should also be standardized to cover possible psychological complications that may arise after transplantation. Respecting this, high levels of anxiety and depression have been detected in the immediate post-transplantation period 194.

According to the Altruistic Renal Donation Protocol of the ONT, it would be advisable for candidates who had been accepted for donation to receive appropriate psychological assistance from the moment they are included in the scheme. This would aid the emotional expression and management of any possible anxiety and suffering caused during the donation process, with the aim of preventing future emotional complications and the development of psychological disorders triggered after donation 172. Identifying which donors could potentially have the greatest post-transplantation psychological problems could help to limit the follow-up of such cases 192, reducing the probability of subsequent complications emerging 195.

• •

  All donors should at least fulfil the GFR thresholds set for their age and sex (Table 7). The thresholds are valid under appropriate conditions of post-donation compensation and preservation of renal function (Quality of evidence: B).

• •

  We recommend that the GFR should be ≥ 90ml/min/1.73 m2 in donors<30 years old; and that the GFR is ≥ 80ml/min/1.73 m2 in donors aged from 30 to 45 years. The absence of additional risk factors should be confirmed in both cases (C).

• •

  The use of the Grams et al. risk calculator [21] is not recommended for young candidates as it may seriously under-estimate the risk of end-stage CRD (ESRD) (B).

• •

  In donors>45 years old with a GFR higher than the minimum rates which are required, but with other risk factors, it is recommended to estimate the risk of ESRD using the Grams et al. risk calculator tool [21] (C).

• •

  We suggest that donors with a GFR<70ml/min/1.73 m2 should not be accepted, except for elderly donors and after a careful assessment (C).

The GFR is now accepted to be the best renal function indicator, in healthy individuals as well as in patients with CRD. In spite of this, there is no clear agreement on what the GFR should be in any specific individual or how the GFR should be adjusted to the changes that occur with age. Much of the literature to date accepts that the average GFR for a young Caucasian male is 125ml/min/1.73 m2196,197. Nevertheless, more recent studies based largely on populations of healthy donors show lower GFR rates for the same average individual, at around 107ml/min/1.73 m2198–200 (Figure 5). In the same way, we have evidence that the GFR falls physiologically after a certain age, although the speed of this fall and its cause are also the subjects of intense debate 201–203. The study of potential healthy donors has shown that there is a constant drop in the GFR after the age of 40-45 years, amounting to approximately 0.9ml/min/1.73 m2 per year 198,199. These data, obtained from studies of the general population as well as candidate donors, have even been used to create a new proposal for the estimation of the GFR and its normal intervals as an alternative to the staging currently used for CRD in the KDIGO guides, so that the classification of CRD and its staging based on GFR thresholds uses limits which are adjusted to the age of the specific individual 204.

Figure 5.

Pre-donation glomerular filtration rates (mL/min/1.73m2) measured (United Kingdom, UK) 215 or estimated rates (Spain, United States, US) 200,237 per age group. The population figures in the United Kingdom correspond to the average of those published for men and women. The figures shown in the population of donors in the United States (US) correspond to representative values for the said population per age group. The figures for the Spanish population correspond to the average in donors of the Spanish Registry of Living Donor Kidney Transplantation 2010-2017.

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These circumstances are important when evaluating a candidate donor and, in fact and in consonance with them, there are now two different approaches in evaluating acceptable or borderline GFR for donation. The first approach is suggested by the KDIGO, and it is the result of classifying CRD in GFR intervals independently of the individual's age. It states that a donor is suitable if their GFR ≥ 90ml/min/1.73 m2 (9). The second approach is proposed by the Guides of the British Transplantation Society, BTS, and it accepts the concept that a physiological fall occurs in the GFR with ageing. It proposes GFR thresholds that are acceptable for donation in the normalcy ranges defined for each interval of donor age (Figure 6) 2. The use of one approach or the other has important consequences in the classification of candidates as suitable or not for donation 205.

Figure 6.

Graph and table showing the minimum estimated glomerular filtration rates (eGFR) for donation to be accepted, according to candidate age for men (-•-), women (- -), and both sexes (-•-) proposed by the latest British Transplantation Society Guides 2, comparing them with the limiting threshold per age group proposed for the definition of chronic renal disease by Delayane et al. 203.

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The aim in both cases is that the GFR after donation will not compromise the prognosis for the donor during their whole life expectancy, with zero or minimum impact on the long-term health of the donor. It is therefore necessary to know the expected donor GFR following donation, and the threshold GFR below which an excess of morbimortality is detected.

• •

  We suggest that donation by young people, especially those who are under 30 years old, should be restricted to candidates who have a GFR of at least the average for their age group, without any additional risk factors and a strictly normal result of evaluation of their health status (C).

• •

  We recommend that advanced age alone should not contraindicate donation, although such candidates are subject to more perioperative risks (A).

• •

  We suggest that hypertension, one of the risk factors for CRD, may have less impact in elderly donors, due to their reduced life expectancy (C).

• •

  We recommend that donor-recipient pairs should be informed that when donors are elderly, especially when they are older than 60 years, the renal function attained in the recipient and probably the long-term survival of the graft may be reduced (B).

Increasing numbers of elderly donors have been accepted in recent decades, and more than 30% of LDKT donors are now older than 50 234. This tendency reflects the change in the perceived long-term risk of ESRD for donors, as this affects younger candidates to a greater extent.

We now recognise that all donors have an increased risk of ESRD. This risk is very small in absolute terms, and it arises over the very long-term after donation (one or several decades), and it seems to increase exponentially with time after donation 223,229,235. Analysis of the donors who have reached a stage of ESRD shows that the majority of these patients took more than 10-15 years to arrive at this point, and they donated when they were young. Donation when young is therefore a risk factor of the first order for donors to reach stages of ESRD 235–238. Only 2% of the donors in the American UNOS registry were younger than 35 years old 223.

Young patients have a very long time of exposure to the risk of new diseases such as hypertension and DM, which usually debut after the age of 45 years. These diseases are difficult to predict, but may affect their future risk of CRD 223. We also know that hypertension and/or DM cause practically 50% of the cases of ESRD in donors, a situation that occurs several decades after donation 238. All these factors reduce the predictive power of a normal evaluation result in young candidates when they donate, and it may lead to an under-estimate of the risk 225. On the other hand, there is less available evidence for how young donors will evolve than there is for intermediate-age donors 223.

All these factors are inversely applicable for elderly donors. Although the latter are exposed to higher risk during nephrectomy and the immediate post-donation period, older donors with CRD risk factors such as hypertension and DM are less likely to be exposed to them for long enough to lead to ESRD 239. In spite of this, age may be a clear limiting factor for donation. According to the detailed analyses in other sections of these recommendations, advanced age is a risk factor for surgical complications during donation, recovery and the development of hypertension after donation 240,241. Donors older than 50 should therefore be subjected to exhaustive cardiorespiratory evaluation 242.

Age is an independent risk factor in for ESRD in donors, with the exception of African Americans 37,224,229. This fact may be due to the higher risk of developing hypertension and DM after donation in the African American population, so that the longer life expectancy in young and intermediate age donors would increase the long-term risk of ESRD 224.

The term “minor” urinary alterations does not always correlate with their importance for an individual's renal prognosis, so that the term “minor” is only applicable when it refers to lower grade urinary alterations that are close to normality.

• •

  We suggest that donation should not be contraindicated if dyslipidaemia is an isolated finding (C).

• •

  We suggest that dyslipidaemia should be taken into account when estimating the overall cardiovascular risk of a donor (C).

The prevalence of dyslipidaemia in the general Spanish population stands at 30%–51%, making it one of the most prevalent cardiovascular risk factors, surpassed only by hypertension in some studies 258. Additionally, within dyslipidaemia, hypertriglyceridemia and low levels of HDL cholesterol form part of the diagnosis of metabolic syndrome 259. Few studies have analysed the possible association between pre-donation lipid levels and the results after nephrectomy. One study in México found that metabolic syndrome had a negative impact, leading to a lower GFR at 5 years, although none of the components of metabolic syndrome that were analysed (abdominal perimeter, fasting glycaemia, hypertriglyceridemia, HDL cholesterol levels or hypertension) had any impact alone on post-donation renal functioning. In an Israeli study donors were found to be at higher risk of metabolic syndrome than the control group 261. However, no studies analyse the influence of dyslipidaemia as an isolated prognostic factor for renal donors. A meta-analysis in the general population found no association between LDL cholesterol levels and the development of ESRD 125. All of the guides consulted (2,4,9,262,263) recommend the determination of the lipid profile in the study of live donors, although none of them sets a limit for non-acceptance.

• •

  We suggest that hyperuricaemia or a history of gout in a donor are not a contraindication against donation (C).

• •

  We suggest that candidates with a history of hyperuricaemia and/or gout should be informed that donation is associated with increased levels of uric acid and perhaps a higher risk of gout (C).

A fall in the GFR is accompanied by a reduction in the excretion of uric acid and a subsequent increase of uric acid in the blood, while the risk of gout also rises 264. Within the context of the fall in the GFR which occurs after donor nephrectomy, an 8% increase has been observed in uric acid levels 6 months after donation in donors compared to healthy controls, and this increase persists 36 months after nephrectomy 210. If we compare donors pre- and post-donation, uric acid was found to have increased by 20% 7 years after nephrectomy and more episodes of gout were detected, although at a low absolute frequency 209. African American, male and older donors are the most likely to suffer gout after renal donation 265. A recent Japanese retrospective study found that donors with higher uric acid levels before donation were at greater risk of developing suboptimum compensatory renal hypertrophy 266.

As well as the risk of gout, high levels of uric acid have been associated with increased cardiovascular risk and the risk of developing CRD in the general population 209,267. These data have not been confirmed in cohorts of renal donors.

Of the recently published guides, only the 2017 KDIGO make recommendation about renal donor hyperuricaemia 204. As the development of hyperuricaemia and gout after donation seems to be strongly associated with sociodemographic factors 265, donors should be assessed on an individual basis, asking about possible episodes of gout and informing them about the potential risk of hyperuricaemia and/or gout after donation.

• •

  We suggest that the impact of smoking on whether candidate donors are accepted should be individualized, depending on the overall risk of the candidate (C).

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  Smoking cessation is recommended before donation as well as during donor follow-up (C).

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  Potential donors should be properly informed of the risks associated with smoking and having smoked (NG).

Tobacco consumption is a major but modifiable cardiovascular risk factor, with a prevalence in Spain of 39% among adults aged from 35-64 years 268. As well as its widely known cardiovascular and carcinogenic risks, smoking may also cause direct renal damage by promoting atherosclerosis and microvascular damage in tissues, and it has been associated with the appearance of CRD 269. The aforesaid meta-analysis on risk factors for developing ESRD in the general population after 15 years showed that active smokers had a 76% increase in risk, while ex-smokers too had a 45% increased risk 125.

There is little literature on the risk for smoking donors after nephrectomy. An American study found a risk of mortality at 12 years to be 5 times higher in donors who were smokers than it was in non-smokers 120.

No guide recommends contraindicating donation for smokers 2,4,9,262,263. They do recommend undertaking respiratory function tests to rule out structural pulmonary pathologies 2 and, depending on the accumulated packs per year index, it may also be necessary to use low radiation thoracic scan imaging to rule out lung neoplasia 263.

• •

  The overall and psychosocial assessment of donor candidates should specifically examine their consumption of alcohol and other drugs (NG).

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  We suggest that all donors should be encouraged to reduce their alcohol consumption to the recommended levels for the general population (D).

There is no evidence or recommendation whatsoever regarding the evaluation of alcohol consumption and/or addiction to other drugs in potential renal donors 2,4,9,262,263. The advice to reduce consumption or to consume alcohol in “moderation” seems to be insufficient to correctly assess donor risk, as alcohol consumption may be associated with the development of hypertension or gout, for example 204. Moreover, addiction in itself should be included within the psychological assessment of donors.

The European guides examined “alcohol consumption” in depth 4. The authors concluded that a reduction in alcohol consumption should not only be recommended but also encouraged and sought. The target was to reduce consumption to below 60 grams per day in men and 40 grams per day in women, according to World Health Organization criteria 270. Although extrapolation from renal recipients to donors should not be the norm, it would seem recommendable to at least evaluate donor alcohol consumption, over and above a simple question such as: “Do you drink?” Alcohol consumption prevalence in the previous 30 days stands at 60% in adults in Spain, and up to 25% of men aged from 55-64 years consume it daily 264. It is therefore necessary to assess alcohol consumption more precisely in our renal donor candidates, so that we can offer suitable information and detect possible alcohol dependency disorders. Excessive consumption can also be identified using indirect signs, such as altered liver function in analysis or ultrasound scan imaging.

On the other hand, there is no evidence or any recommendation on assessing donors for sporadic drug consumption. In fact, the majority of guides contextualise drug consumption within their donor assessment in terms of infectious diseases. Within this scenario, psychological assessment is the most important means of ruling out problems with addiction, so that the decision whether to accept a donor is based on their complete psychological and medical evaluation.

• •

  We suggest that the body mass index (BMI) should be used for the clinical evaluation of overweight and obese subjects (Quality of evidence: C).

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  We suggest that individuals with a BMI>35kg/m2 should be advised against renal donation (C).

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  We recommend that living donor renal donation should be contraindicated in obese patients with a second risk factor (B).

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  We recommend that obesity (BMI>30kg/m2) should be considered a relative contraindication against donation, and that this should be evaluated on an individual basis to detect the presence of other cardiovascular risk factors such as glucose intolerance, hypertension and proteinuria (B).

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  We recommend that obese donors should be advised on the increased risk of perioperative morbidity and the lack of data on long-term safety (B).

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  Donors with a BMI >27kg/m2 should be informed that they may be at higher long-term risk of developing CRD and that therefore, they should lose weight prior to donating and keep to a healthy weight afterwards (C).

Being overweight or obese is a public health problem due to its high rate of prevalence in the general population, as a result of a sedentary lifestyle and overeating. National Health Institutes define obesity as a BMI≥30kg/m2. Although historically living donors were free of pathologies, the selection criteria for marginal donors have been gradually broadened 271. Currently more than 25% of living donors are obese at the moment of donation, as opposed to 8% in the 1970s, and up to 43% are overweight.

Obesity is an independent risk factor for ESRD in the general population. It may cause functional and structural changes at renal level, such as glomerular hyperfiltration, glomerulomegalia and focal segmental glomerulosclerosis lesions. The risk of ESRD increases in patients with a solitary kidney, who develop compensatory glomerular hyperfiltration. Patients with a BMI >30kg/m2 at the moment of nephrectomy are therefore at higher risk of developing proteinuria and renal failure 10 years afterwards, due to reasons other than renal donation 272.

Obesity is associated with a higher risk of hypertension, DM, CRD, metabolic syndrome and cardiovascular disease in the general population, and this is also the case in living donors. Although BMI is a useful tool in the identification of overweight and obese patients, there is no established agreement on what constitutes a safe BMI for donors, and there are several different recommendations 2–4. The long-term impact of obesity on donors is therefore uncertain, and it is hard to find the limit that would predict a higher post-donation risk, so that candidates could be excluded during the pre-donation assessment, or lifestyle strategies could be implemented to modify this factor.

Obesity in living renal donors does not seem to affect their long-term health, except for a more complicated wound and a longer time in surgery. There are no differences in the GFR in comparison with non-obese donors in the years following donation 213,273. However, the long-term impact may be negative. In a national study in the U.S.A., obesity alone (without hypertension or DM) was associated with a higher rate of CRD and mortality in comparison with non-obese donors 271. They also developed DM and hypertension more often and earlier than donors who were not obese after donating 274,275, although this risk was not aggravated by the nephrectomy 276.

The above findings have important implications for the selection of living donors in terms of the BMI cut-off points set previously as contraindications for donation. It therefore varies from a BMI of 30kg/m2 to 35kg/m2, depending on the hospital. Being overweight may lead to a high risk of ESRD in the long-term in comparison with a normal BMI, so that potential donors who are obese or overweight should be advised to lose weight before donation. Moreover, a lower BMI is associated with an improvement in other cardiovascular risk factors over the short-term. Donors with normal BMI at the time of donation underwent significant weight loss prior to donation and kept a healthy bodyweight afterwards; donors with a BMI ≥25kg/m2 at the moment of donation underwent a significant weight gain during 1 year after the donation, suggesting the need to improve weight control efforts among obese renal donors and those with excess weight before and after donation to reduce their risk of advanced CRD 277.

To summarise, obese potential donors should be evaluated on an individual basis to detect other risk factors associated with CRD, such as glucose intolerance, hypertension and persistent proteinuria. Potential donors with metabolic syndrome should be evaluated individually, given the reversible nature of the alterations. Post-donation evaluation and follow-up to control weight, as well as to underline the importance of daily physical exercise and coordination with nutritionists for individualized healthy diet programmes should be an objective in living donor KT programmes, to minimise cardiovascular risks and to improve long-term renal survival.

• •

  We suggest that arterial blood pressure should be measured at least twice, separated by an interval (C).

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  We suggest that arterial blood pressure should be measured in the following cases: donors with hypertension under treatment, when measurement in the surgery shows raised blood pressure >140/90mmHg or normal-raised>130/85mmHg (C).

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  Eligible donors with controlled hypertension<140/90mmHg with one or two antihypertensive drugs, without evidence of organic harm that could be due to hypertension. Consider excluding donors with controlled hypertension but also with other associated risk factors, such as obesity, smoking or advanced age (C).

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  We suggest that potential donors with a blood pressure>140/90mmHg who are under antihypertensive treatment or signs of organic lesion should be excluded (C).

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  We suggest that blood pressure and other modifiable risk factors should be monitored annually after donation (C).

In the general population, the prevalence of hypertension in adults is estimated to stand at 30%-45%, reaching 60% in individuals over the age of 60 278. Hypertension is a relative contraindication for living renal donation, and individual assessment is necessary to determine whether there are any other associated comorbidities. The most recent clinical guides set an arterial blood pressure of >140/90mmHg with one or two antihypertensive drugs or evidence of organic damage induced by hypertension as contraindications for living renal donation. Nevertheless, the definition of hypertension may undergo slight variations over time 279.

A meta-analysis that included 48 studies in 28 countries with 5,145 living renal donors found an average weighted increase in systolic blood pressure of 6mm Hg, while the diastolic increase was 4mm Hg, which is higher than what would be foreseen in normal ageing 122. Donor may be at greater short - to long-term risk of developing hypertension 280–284. The associated risk factors are age, male sex, African-American ethnicity, a family history of hypertension, BMI and higher systolic and diastolic blood pressure. Nevertheless, given that these risk factors are similar to those in the general population of the Framingham cohort, it may be inferred that the effect of nephrectomy neither modifies nor increases the risk 283.

Donors with pre-existing hypertension maintain a higher blood pressure beforehand and two months after donation than their controls. They are similar at 5 years, and no differences in renal function or proteinuria have been found 285.

Although the majority of hospitals exclude patients with hypertension as renal donor candidates, they usually base this on blood pressure measured in a clinical examination, and this does not reflect their real blood pressure. In a study of 178 donors, 63 of them had hypertension when measured in the surgery, but two thirds of these were found to correspond to “white coat hypertension”, as when ambulatory blood pressure monitoring (ABPM) was used, these patients were found to be eligible for donation. On the contrary, of the 115 individuals found to be normotensive in clinical measurement, 17% were found to have masked hypertension in the ABPM, and they were excluded from donation. The individuals with masked hypertension were older, male and had a somewhat higher clinical blood pressure than the individuals with sustained normotension 286. ABPM better reflected the real blood pressure than measurements in the surgery. Several studies have pointed to the value of ABPM in renal donors when clinical measurement of blood pressure is in the hypertensive range. 30%-60% of potential donors who had hypertension during clinical assessment were found to be normotensive when studied using ABPM 287.

Eligible hypertensive donors should therefore be appropriately monitored using by ABPM and have no evidence of hypertension-induced organic harm. In the same way as for the general population, it is probable that a rise in blood pressure in living renal donors will increase their cardiovascular risk and the risk of CRD. The first therapeutic step would be to administer renin angiotensin system blockers. The donors without pre-existing hypertension should be informed that donation may accelerate the increase in blood pressure respecting what would be expected with normal ageing, and that it is necessary to monitor blood pressure regularly.

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  We recommend that basal glycaemia and glycated haemoglobin (HbA1c) should be determined in all donors (B).

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  We recommend that an oral overload glucose test should be performed if there is a history of gestational diabetes, a first-degree family history of type 2 diabetes, impaired fasting glycaemia, overweight, hypertension or dyslipidaemia (B).

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  Donors with type 1 DM should be excluded (D).

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  Donors with type 2 DM should generally be excluded, although they may be considered under special circumstances (C).

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  In cases with pre-diabetes or metabolic syndrome the decision should be taken on an individual basis (D).

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  Recommendations for a healthy lifestyle (C).

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  Follow-up after donation to monitor CV risk factors (C).

There has been a major increase in the prevalence of DM over recent decades 288,289. Potential renal donors should have a determination of basal glycaemia and glycated haemoglobin (HbA1c), In those ones with a first-degree family history of type 2 diabetes, a history of gestational diabetes, impaired fasting glycaemia (IFG), obesity, hypertension or dyslipidaemia, an Oral Glucose Tolerance Test (OGTT) should be performed.

Maintained hyperglycaemia triggers a series of haemodynamic and structural changes which, when they coincide with a genetic basis and converge with other factors such as obesity or hypertension, may lead to the appearance of diabetic nephropathy 290,291. If this is combined with hyperfiltration due to reduction in the nephron mass after nephrectomy, the risk of developing diabetic nephropathy in renal donors with diabetes may be considerable. The presence of type 1 DM has therefore classically been considered to be an exclusion criterion for renal donation. Nevertheless, in type 2 DM and under certain circumstances, especially if there are no other factors such as hypertension or overweight, donation may be considered 292. In a series of 225 donors, the 14 diabetics at the moment of donation were compared with the 211 non-diabetics over an average follow-up time of about 4 years. There were no differences in renal function or albuminuria between both groups 293. Another series found no differences in survival over the long-term, and none of the diabetic donors had advanced CRD 294.

Up to 70% of prediabetic individuals (basal glucose from 100mg/dl to 125mg/dl, or an altered OGTT) will develop type 2 DM 295,296. The proportion of donors with glucose intolerance has increased from 7% to 22% over the past two decades 297, and studies carried out with donors of this type show good outcomes, without differences in the GFR or albuminuria after 10 years of follow-up in comparison with non-prediabetics 298. A study of 93 donors with HbA1c and OGTT distributed them in three groups: high risk of DM (HbA1c and OGTT in the prediabetic range), low risk (one of both parameters altered) and the control group (with both parameters normal). After an average follow-up time of 76 months, a high percentage of the high risk group developed DM, in comparison with the low risk group and the control group (31.3% vs 6.5% vs 0%). They showed no higher risk of hypertension or microalbuminuria, and the prediabetic donors had a similar GFR to the control group. The conclusion was that although HbA1c identifies prediabetic donors at risk of progressing to DM, with careful selection these donors would not be at higher risk of renal function deterioration 299.

Notwithstanding all of the above, these results should be interpreted with caution since there is no long-term follow-up. A study of 2954 living renal donors found that after an average follow-up time of almost 18 years, 154 had developed type 2 DM. During the first decade, they had no increased risk of CRD after developing diabetes, although this was not the case for increased albuminuria 300. In a later publication this same group presented the outcomes of these diabetic donors, and over the longer term they showed faster deterioration of the GFR than the non-diabetic control group if they also had hypertension and proteinuria 301.

Several risk indexes have been prepared for the general population to estimate the probability of developing type 2 DM, but their predictive capacity varies widely as they exclude major risk factors. In practice, basal fasting glucose and the OGTT are the standard recommended tests for the diagnosis of type 2 DM, in renal patients too. Figure 7 shows a flow diagram that may help to detect type 2 DM before renal donation.

Figure 7.

Possible mechanisms which lead to hyperfiltration, progressive renal disease and proteinuria in potential living renal donors who have metabolic syndrome prior to donation. GFR: Glomerular Filtration Rate. Adapted from Hernández D 305.

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Metabolic syndrome arises when at least three of the following circumstances coincide: abdominal perimeter (waist circumference) >102cm in men and >88cm in women, fasting serum triglycerides ≥150mg/dl, HDL-cholesterol <40mg/dl in men and <50mg/dl in women, systolic blood pressure ≥130mmHg and/or diastolic≥85mmHg or taking antihypertensive drugs and fasting glucose ≥100mg/dl or taking hypoglycaemiant drugs. This syndrome has a prevalence in Spain of 25%, and it is associated with CV morbimortality, diabetes and renal damage 302–304. The high prevalence of metabolic syndrome, its comorbidities and its negative consequences, make it necessary to undertake an exhaustive search for this entity in potential renal donors 305. Metabolic syndrome and each one of its components are independently associated with a higher risk of CRD 306. However, it is less clear whether the presence of metabolic syndrome in a donor is associated with worse renal function after donation. In this respect, an interesting study analyses the association between the syndrome, renal function and histological damage in living renal donors. Of a total of 410 donors, 12% had metabolic syndrome at the time of donation; the pre-implantation renal biopsies of the donors with metabolic syndrome showed more histological signs of chronicity, and this finding was associated with slower recovery of the GFR after donation 307. One group of renal donors with metabolic syndrome reached a GFR <70ml/min in a shorter period of time (an average of 5 years vs 12 years) 260. Theoretically, in individuals with metabolic syndrome who are subjected to nephrectomy for living donation, insulin resistance and the fall in renal mass may predispose their remaining kidney to hyperfiltration, with proteinuria and progressive renal disease (Figure 8).

Figure 8.

Flow diagram for the detection of diabetes mellitus before living donation. OGTT: Oral Glucose Tolerance Test; AOGTT: Altered Oral Glucose Tolerance Test; AFG: Altered Fasting Glucose. DM: Diabetes Mellitus. Adapted from Hernández D et al. 305.

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In potential donors with type 2 DM, prediabetes or metabolic syndrome, changes should be recommended in lifestyle, diet, weight loss and physical exercise. The aim would be to prevent progression to diabetes and reduce CV risk and the risk of progression to CRD 308.

The benefits of weight reduction to slow the development of diabetes have been clearly proven, at least in the short-term 309–311. However, this benefit is not usually maintained over time, above all because the partial or total recovery of the weight that had been lost is very common over the long-term 312.

Physical exercise has also been shown to be effective in slowing the progression to diabetes 50. The ADA recommends at least 150minutes/week of moderate to vigorous physical activity, or shorter periods (at least 75minutes/week) of vigorous intensity exercise to prevent or delay the appearance of type 2 DM in high risk populations and/or those with prediabetes 313. Intermittent high intensity training and continuous moderate intensity training have a similar positive effect on functional capacity and cardiometabolic markers in individuals with prediabetes or type 2 DM 314–315.

• •

  An ABO blood group and HLA compatible transplant offers the best opportunity of success (Quality of evidence: A).

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  Incompatibility in ABO blood group and the HLA system are independent. Donor and recipient may be HLA identical and ABO incompatible (NG).

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  We recommend that blood group should be determined at an early stage in the study of a potential KT donor-recipient pair so that expectations can be properly managed and transplant options can be discussed (B).

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  ABO blood group incompatibility is not an absolute contraindication for transplant, and it can be resolved by paired KT or a desensitizing treatment (A).

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  To evaluate the transplant options for an ABO incompatible pair it is essential to quantify the isoagglutinins (ABO antibodies) in the recipient, preferably using donor erythrocytes (B).

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  HLA should be typed using molecular biology methodologies (B).

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  We recommend that HLA should be typed at allelic level (2 fields) and in the 11 loci HLA, that is: HLA-A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPA1 and DPB1, in the recipient as well as in the possible donors (B).

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  High resolution HLA typing makes it possible to interpret whether the recipient has donor-specific antibodies (DSA), detected using the new techniques for studying anti-HLA antibodies (NG).

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  The new solid phase techniques have higher sensitivity to detect anti-HLA antibodies in comparison with the classic cellular techniques (A).

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  The moment for studying histocompatibility should be decided on the basis of the characteristics of the recipient and the potential donors to prevent unnecessary examinations, guiding the expectations of the donor and recipient (NG).

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  We recommend that a detailed clinical immunological history of the recipient should be prepared, and this should be shared with the histocompatibility laboratory, including their potentially sensitizing events and the relationship between the recipient and potential donors (NG).

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  It is important to show whether the potential donor is the father of the descendants of a female recipient or whether the donor is the son of a female recipient, given the risk of sensitization during pregnancies.

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  Changes should be shown in immunosuppression if the recipient still carries a dysfunctioning graft.

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  We recommend that a crossmatch test should always be performed between the donor and recipient (A).

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  A virtual crossmatch test will give us an initial approximate idea of donor and recipient compatibility (NG).

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  A cell-based crossmatch test should be performed before transplantation, with cytotoxicity techniques and flow cytometry between the donor and recipient (NG).

• •

  The histocompatibility laboratory or a trained professional in this field should interpret the test data and advise the clinical team on the risk for the donor-recipient pair (NG).

Human KT became a reality in the 1950s after performing the procedures on identical monozygotic twins as donor and recipient 316. The required technical and surgical advances had occurred deces earlier. This underlines the fact that the most important barrier for the survival of a solid organ transplant lies in the potential immunological “incompatibility” with the donor, which may trigger the loss of the graft 317.

All of the molecules which are present in the donor but absent in the recipient are able to cause a potential immune response. Nevertheless, the barriers idntified in clinical practice which clearly generate incompatibility and possible rejection are:

• -

  Blood group incompatibility, due to the presence of antibodies which are naturally present in any individual older than 4 months.

• -

  Incompatibility in the Human Leukocyte Antigen (HLA) system, due to the presence of antibodies acquired by previous contact with HLA antigens.

More than one third of potential KT recipients have developed anti-HLA antibodies that may hinder compatibility 318. Incompatibility in both of these systems is independent. The gene involved in the definition of the ABO blood group is located in the long arm of chromosome 9, and the genes which encode the HLA antigens are located in the short arm of chromosome 6. This explains the fact that two brothers may be HLA identical and nevertheless also ABO incompatible.

However, it is possible to transplant a non-compatible organ but with different levels of HLA mismatches between the donor and recipient. The probability of rejection is associated with the number of HLA loci mismatches between the donor and the recipient, Greater match between them is related to the increase in graft survival 319.

The new techniques used to detect anti-HLA antibodies are more sensitive, and it is increasingly common to find living donor and recipient pairs who are HLA incompatible, especially in individuals with a very high cPRA, which makes it very difficult to find a compatible donor 348. For such individuals, and also for any potential recipient with anti-HLA antibodies, we suggest using this workflow for the recipient together with the potential living donors to achieve a KT from the living donor who is the best option in terms of quality. It is also an opportunity to evaluate the risk in detail, making it possible to fully plan the transplantation and the corresponding treatment.

Figure 11.

Working algorithm showing recipients and potential living donors to achieve kidney transplantation with a living donor as the best option.

(0.52MB).

To summarise, it is essential to have a good characterization of the immunological risk and the opportunities for the recipient, through a good immunological history. Individuals with a high level of HLA sensitization would benefit from the possibility of donation by a HLA-identical sibling, even if they were ABO incompatible, because as we will see in the specific chapters, ABO desensitization treatment is more effective than HLA desensitization. If they have no identical siblings, the possibility of having a higher level of HLA compatibility (a lower level of incompatibility) would lie in genetically related family members. If although no compatible living donor is found there is the wish to donate, the intensity of donor-specific anti-HLA antibodies in the recipient should be evaluated and the options of paired KT or HLA desensitization should be considered. It is sometimes possible to study a potential living donor while the patient is included in the deceased donor waiting list, to increase transplant options for a sensitized patient.

• •

  Left nephrectomy is usually preferred in live donors, although right nephrectomy may also be performed, with similar complications (Quality of evidence: NG).

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  Living donor nephrectomy when there are multiple vessels or anatomical alterations should take place in more experienced hospitals (NG).

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  We recommend that donors with widespread atheromatosis or fibromuscular dysplasia of both renal arteries should be rejected (NG).

Once the viability of donation has been confirmed on the basis of medical workout, the donor should be physically examined and the results of their angiotomography should be thoroughly reviewed. It is important to know the surgical history of the donor, to prevent possible complications during the operation. Donor weight and more specifically their physical examination will be important when selecting the surgical technique. If the aim is to perform a transvaginal nephrectomy, a digital vaginal examination should be performed prior to the surgery to confirm good elasticity that will permit the safe harvesting of the organ. In the case of a LESS nephrectomy the donor should be thin and without a history of major abdominal surgery (because it may have created adherences).

The anatomical evaluation of donors should include angiotomography with arterial, venous and nephrographic phases to identify any possible alterations in the urinary tract, and/or the vessels. This exploration has a sensitivity/precision of over 95% in the detection of renal veins and arteries 350,351. The radiologists will be in charge of supplying exact anatomical information, based on their own experience.

If both kidneys are similar, it is preferred to collect the left one as it has a longer vein, making it easier to engraft. The laparoscopic harvesting of a right kidney is not a contraindication nowadays, and it accounts for 15%-20% of nephrectomies in the majority of series. A higher rate of graft thrombosis in right living donor nephrectomies was described in the past. Several subsequent studies have shown similar results for organs from both sides (2D) 352. To facilitate renal transplantation with short veins, a transposition of the iliac vein in the recipient may be performed, as this reduces the space between veins in the anastomosis 353.

Variants and vascular alterations

During the study of a living donor we may find different situations that have to be evaluated separately, while also taking into account the characteristics of the recipient. One such situation consists of complex bilateral renal pedicles (multiple arteries and veins, fibromuscular dysplasia of the intima, calcifications in the arterial ostium and even aneurisms).

Kidneys with multiple pedicles are now accepted in the majority of hospitals, and they have been shown to give good functional results 354,355. In cases where there are multiple arteries it is preferable to obtain a single anastomotic opening by bench surgery on the graft whenever this is possible. When the arteries have similar calibres they should be joined laterolaterally in a “shotgun barrel”. When the arteries have different calibres, the smaller ones are anastomosed to the larger one (terminolaterally) using discontinuous or continuous stitches in Prolene 7/0 (Figure 12A). If the anatomy makes this necessary, it is possible to do independent anastomoses. In those cases where the renal artery has been sectioned after the bifurcation, so that we have short vessels, the hypogastric artery and its branches in the recipient may be used to obtain a viable vessel (Figure 12B).

Figure 12.

A: Shotgun barrel anastomosis and terminolateral anastomosis in a kidney from a living donor. B: Use of the hypogastric artery to obtain a single artery. C: Atheroma plaques in the ostium. D: Fibromuscular dysplasia of the unilateral intima. Bench surgery repair with a cadaveric graft. E: Repair of arterial aneurism by means of cadaveric arterial graft in bench surgery. F: Exeresis of a tumour in bench surgery.

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When there are upper polar vessels, these can be eliminated when they are small (<2mm) as they do not represent a significant loss of renal function. This is more controversial for the lower polar vessels, as these irrigate the urethra and ligating them may cause urinary tract ischemia. To avoid this tract ischemia an anastomosis can be done between the urethra of the donor and the recipient's one.

In the case of multiple veins, one of them can be ligated if they are of different diameters. When the veins are similar we should anastomose them to each other, ensuring good venous drainage. As older donors are now accepted atheromatosis at the level of the renal artery ostium is frequently observed. When this atheromatous plaque is large and bilateral, the donor should be rejected (Figure 12C). If these plaques are unilateral, the kidney can be collected while taking special precautions during the harvest. It is important to place clips with sufficient separation to border the plaque.

Fibromuscular dysplasia may affect the renal arteries. This consists of a heterogeneous group of changes in the arteries that are neither atherosclerotic nor inflammatory, and they cause a certain degree of stenosis, occlusion or vascular aneurisms which may restrict the renal flow. Donors will be rejected if they have bilateral involvement. They may be accepted if the dysplasia is unilateral, with replacement of the affected area in bench surgery using a cadaveric tissue graft (Figure 12D).

Renal artery aneurisms are rare, and they generally affect the arterial division. They are at risk of rupture when they are larger than 1.5cm and not calcified. Nephrectomy in a donor with an aneurismatic artery is therapeutic. The affected kidney may be repaired in bench surgery using a cadaveric tissue graft or the internal iliac of the recipient (Figure 12E).

• •

  Laparoscopic nephrectomy of a living donor is the technique of choice as it causes less postoperative pain and results in a shorter hospitalization and convalescence than open surgery (NG).

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  Living donor nephrectomy by lumbotomy may be indicated when the donor has had multiple abdominal interventions and intra-abdominal adherences (B).

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  Living donor nephrectomy using a mini-incision is a valid option for donation (NG).

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  LESS or transvaginal living donor nephrectomy should be performed in experienced hospitals (NG).

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  Robot-assisted living donor nephrectomy gives similar results to laparoscopic techniques, although it is more expensive (NG).

The experience of the surgeon should be taken into account when selecting a surgical technique, to minimise complications and obtain a good quality organ. Traditionally the surgical technique of choice for living donor nephrectomy was open surgery through a lumbotomy, which was associated with a high rate of morbidity and a high risk of eventration. Increased experience in laparoscopic surgery means that this technique is now used in the majority of hospitals with good results for donors and recipients, minimising complications 364,365. Due to this, laparoscopic nephrectomy of the donor is now the technique of choice 366.

All of the minimally invasive techniques require that the donor be in lateral decubitus, with 3 or more trocars in place through the abdominal cavity. The path for renal harvesting will vary depending on the technique used, and it may be a periumbilical incision, a pfannestiel, in the iliac fossa or transvaginal.

Live donor nephrectomy by lumbotomy is not considered a technique of choice, as it requires a larger incision and therefore involves more postoperative pain and longer hospitalization. Living donor nephrectomy through a lumbotomy may be considered in certain circumstances, when the donor has had multiple abdominal interventions and has intra-abdominal adherences.

Different techniques have been developed as alternatives, using an anterior mini-incision, in the side, subcostal or posterior, giving simple access to the kidney 367. Randomized studies which compared surgery using a mini-incision with classical open surgery and laparoscopic surgery found that surgery takes longer with the mini-incision than it does with classical lumbotomy, although it causes less morbidity in the donor (with less need for analgesics and a faster recovery). In comparison with laparoscopic surgery, donors require more analgesia and recovery time is longer. No significant differences were found in terms of the functional results of the graft between any of the three techniques 368,369. The micro-incision technique makes it possible to perform a nephrectomy with low morbidity and good functional results, so that it is a good alternative in certain circumstances when laparoscopy is still not viable 370.

• •

  If a right kidney is used with a very short vein, we recommend that bench surgery should be used to create an optimum length renal vein by reconstruction and lengthening techniques with saphena and gonadal vein (Quality of evidence: B).

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  We do not recommend routinely administering thromboembolic prophylaxis to all recipients using low molecular weight heparin (C).

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  We recommend that single dose antibiotic prophylaxis should be administered (A).

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  We recommend that the lymph glands should be ligated or coagulated to prevent the appearance of lymphocele. (A).

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  We recommend that the kidney should be kept cold during surgery, wrapping it in a gauze containing crushed ice, or placing it in two gauzes with ice above and below the kidney (B).

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  We recommend that the shortest possible length of urethra should be used for anastomosis in the bladder, while keeping the periurethral fat to ensure good irrigation (B).

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  We recommend that a Lich Gregoire-type extravesical re-engraftation should be used in a double J (A).

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  We recommend that a prophylactic mesh should be used in obese and diabetic patients, and/or patients treated with mTOR inhibitors (A).

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  Robotic KT gives good results over the medium term and in the near future may be an alternative to open surgery (NG).

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  RKT is restricted to selected recipients as it has a higher rate of retarded graft functioning and arterial thrombosis, and it cannot be used in patients with advanced atherosclerosis (NG).

In 2015 two hospitals carried out the first completely robotic transplants in Europe, and since then many experiences in specialized hospitals and multicentre series have been published 416,417. Robotic KT is an alternative to open surgery, and it is feasible, reproducible, safe and has surgical advantages when performing vascular anastomoses and urethral re-implantation. This is partly due to the increase in vision and great freedom of movements offered by the robot. It has also been suggested that this technique may reduce complications, the length of hospitalization and postoperative pain, while giving better cosmetic results than open surgery 418,419.

RKT involves complex surgery with multiple steps, and it requires the complete domination of robotic surgery. Surgical time should not be excessively prolonged, and proper fluid management is essential, with appropriate intra-abdominal pressures. This makes it possible to prevent the potential reduction in renal flow and pneumoperitoneum, as well as prolonged surgery 420–422. Some groups have described good results during the first year of development 423–426.

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  We suggest that imTOR should substitute calcineurin inhibitors when patients cannot receive the latter (C).

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  We recommend that belatacept should be given to patients who cannot receive calcineurin inhibitors (B).

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  We suggest that belatacept should be restricted in patients with positive Epstein-Barr virus serology (C).

Some trials suggest that the imTOR give better renal function at one or two years, although they do not improve graft survival 522,523. It also offers less long-term risk of malignity 524. Other studies associate the imTOR with increased risk of death due to a cardiovascular or infectious cause 524, dyslipidaemia, lymphoceles, medullar toxicity 522 and acute rejection 524. Although it seems to be safe when used as an alternative in patients who react to cyclosporine as toxic 525, administering it instead of tacrolimus is associated with an increase in the rejection rate 526, which has also been confirmed in LDKT 527,528.

Although Belatacept is associated with better long-term graft functioning than cyclosporine, it has a higher rate of acute rejection and lymphoproliferative disorders after transplantation, especially in patients with previous negative serology for EBV 529–531. In comparison with tacrolimus it has a higher acute rejection rate with a variable effect on long-term renal functioning 532,533, although it is an alternative in case of toxicity with calcineurin inhibitors 534,535.

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  We recommend that related LDKT should be the renal replacement therapy of choice in children, and it is recommended that it should be considered at an early stage, to avoid the transitory stage of dialysis (Quality of evidence: B).

KT is the ideal universally accepted treatment for ESRD in children, with countless advantages over other alternative renal replacement therapies such as haemodialysis in hospital or at home, or peritoneal dialysis. Paediatric nephrologists agree that early KT should take place to avoid the transitory phase of dialysis; this makes it possible to minimise the impact of renal disease while reducing institutional as well as community healthcare costs. It also has countless social and familial advantages. It is exceptional for a child to be definitively excluded form a KT scheme, and when this does occur for medical, surgical or psychosocial reasons, it is always temporary.

In spite of the above considerations, early KT is only achieved in our context in 40% of patients, and overall LDKT represents 20%-30% of all paediatric transplantations 29.

Different registries show a worldwide tendency for KT to be the most widespread paediatric therapy. Nevertheless, this varies between countries due to differences in per capita income and national policy respecting preference for donation to children 536. Thus with little variation between countries, the average incidence in Europe of replacement renal therapy in children stands at 6 new patients per year per million inhabitants younger than 14 years 537. However, the rate of KT varies quite widely: in the Scandinavian countries, France, Austria and Spain more than 85% of their population under 14 years old and in renal replacement therapy have received a KT, and this datum is harder to obtain in registries that do not include the whole national population 538,539. Europe in general has a policy of giving priority to paediatric transplantation over dialysis 540,541.

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  We recommend that LDKT in childhood is the option which gives the best results in terms of survival in the treatment of CRD (B).

The widespread belief that KT is the best renal replacement therapy in children and should be the first choice means that the ideal donor has to be found. In general related LDKT, especially from parents to children, is normal practice in transplantation programmes worldwide, and it is almost exclusive in some countries in comparison with deceased donor transplantation. In terms of efficacy, the ONT describes LDKT as “the therapy which offers the best survival results in the treatment of chronic renal failure”542. Its use in children is justified by two needs; firstly there are too few deceased infant donor organs to meet existing paediatric demand, and there is also no preferential option for deceased adult donor KT, and secondly it is necessary to ensure the best results over the short to medium terms. Living donation must be supported by an organizational system which guarantees the absence of coercion or economic reward for donors, although these problems do not arise in donation by parents to their children.

The existence of a good national system to govern living donor programmes also makes paediatric paired KT possible, when due to donor-recipient incompatibility transplantation is impossible with the selected pair. In these cases donor-recipient pairs can be matched within a single hospital or within a strict national scheme which enables simultaneous transplantations 543,544. Apart from immunological compatibility, other advantages of living donation are that transplantation can be planned to take place at the best moment for the recipient, and donor-specific desensitization can take place for recipients with anti-HLA or another type of antibodies. Finally, it ensures better graft survival in children with anatomical vascular or urological difficulties that would make re-transplantation option far more complex or even impossible. The main contraindication against living donation is the potential risk for the donor, or the risk of relapse of the primary disease in the graft.

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  We suggest that the recipient should be informed about the transplantation process in a way that is suitable for their age, obtaining their informed consent and taking their opinion and desires into account (NG).

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  The greatest difficulties in paediatric transplantations arise at the age limits of the same (new-born babies and adolescents), which are intrinsically special risk groups (NG)

Potential paediatric LDKT recipients should be treated in a paediatric hospital by specialists who are aware of all of the specific aspects associated with the primary disease as well as those intrinsic to infancy. The latter are physical (growth, development and maturing) as well as psychosocial factors which are fundamental for the transplantation process (socioeconomic status, degree of dependency, adherence to therapies, etc.). Paediatric recipients should also be informed in a way suitable for their age about the transplantation process, so that they are able to give their informed consent, while taking their opinions and desires into account.

The extreme paediatric ages (new-born babies and adolescents) are a priori the ones which give rise to the greatest difficulties when carrying out a transplantation, and they are groups at special risk 545–547.

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  LDKT in extremely small recipients (in terms of their age or weight has a higher rate of primary graft failure, chiefly due to vascular factors (arterial and venous thrombosis) (A).

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  We recommend delaying transplantation until the recipient is two years old or 10Kg (B).

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  It is exceptionally possible to perform a KT in recipients weighing from 6 to 10 Kg in experienced hospitals, after careful study of the balance between risks and benefits (D).

Children under the age of 2 years suffer the highest rate of morbimortality in all forms of renal replacement therapy 545,548. Commencing replacement therapy during the first year of life is associated with a mortality-independent relative risk 3 to 6 times higher than other age groups 545,548.

In the paediatric population starting replacement therapy with KT has better results over the short to medium term than dialysis. However, this finding has not been completely corroborated in children under the age of two years 548,549. KT is not used universally for children under the age of 2 years and most especially those under the age of 1 year; 99% of these patients start treatment with dialysis, especially peritoneal dialysis 545,548–550.

Commencing KT programmes in extremely small recipients is associated with a higher number of vascular complications, especially arterial and venous thrombosis, as well as primary graft failure. These complications are especially frequent when the donor too is very young, and many programmes reject such young donors for small recipients 551.

Surgical considerations and perioperative and postoperative management are fundamental when performing a KT in a patient less than 2 years old or less than 10 Kg in weight 536,550,552–554. In these patients a suitable policy of haemodynamic monitoring and supply of colloid and crystalloid fluids are associated with good results, preventing early graft loss due to technical causes such as vascular thrombosis, lack of primary function or acute tubular necrosis 550–554. The few experiences when recipient weight is lower than 6 kilogrammes are generally negative 551–552.

We can therefore definitively consider recipients over 2 years old and 10 Kg in weight to be suitable for KT; until then, the best replacement therapy is peritoneal dialysis, and KT should be postponed until the above weight and/or age have been reached, if circumstances make this possible. Exceptionally (in case of peritoneal or vascular access failure or other types of risk) it will be possible to perform a KT in recipients weighing from 6 to 10 Kg in experienced hospitals, after carefully balancing the risks and benefits. Given the major risk of graft loss, KT should not be performed in recipients who weigh less than 6 Kg. Finally, performing KT in very small recipients requires a multidisciplinary team that includes highly experienced surgeons and/or urologists, anaesthetists, nephrologists, intensive care specialists, nutritionists and wide-ranging support by other paediatric specialists. For technical reasons this type of transplantation should be performed in paediatric referral hospitals.

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  We suggest that a multidisciplinary approach should be used in patients aged from 13 to 18 years, chiefly in the process of supplying information before and after KT, to reduce the risk of non-adherence to treatment (D).

The paediatric population from 12 to 18 years old who are candidate KT recipients are also going through the gradual process of becoming independent and responsible; this makes this population especially vulnerable to non-adherence to therapy and a permanent risk of rejection 553,554. Registry data also show an increase of graft loss due to non-adherence to therapy, reaching a maximum at from 13 to 21 years old, after which it falls 555.

Establishing a temporary contraindication against LDKT in an adolescent who does not adhere to treatment would seem to be obvious. Nevertheless, prolonged treatment with dialysis does not seem to mitigate the subsequent risk of failure to comply with therapy 556. In such cases the process of informing the patient before, during and after transplantation and the support of social workers and psychologists who specialise in adolescents is useful in preventing a lack of adherence to therapy 555,556.

Given that the highest percentage of graft losses occurs during the transfer process, it is fundamental to ensure a smooth transition to adult units for these recipients.

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  Living donation by a parent to a very young baby involves a reduction in blood volume of from 33% to 50%, and the surgical approach and perioperative management are fundamental (B).

KT from an adult donor to a very small recipient is a habitual practice which requires initial higher pressure perfusion, and it may lead to a 33% to 50% reduction in blood volume, so that surgical, perioperative and anaesthesia management are fundamental 550,557,558.

Surgical approach: an adult kidney for a paediatric recipient, and most especially if it is for a very small child, will involve a size discrepancy between the donated kidney and the abdominal cavity of the recipient. This may lead to compromise of the space, hindering the creation of the vascular anastomoses and closure of the abdomen after positioning the graft, with compartmental syndrome. The extraperitoneal approach using Gibson's incision is the procedure of choice in KT to babies, for living as well as deceased donors. Nevertheless, doubts may arise when the recipient is very small or has abdominal problems of another type. An intraperitoneal approach is recommended when the recipient weighs less than 15 kilos, with the advantage of offering a larger surgical field and wider exposure of the major vessels, although it also has the disadvantage of possible intestinal obstruction 559. In any case, the approach should be selected on the basis of the conditions of the recipient and the experience in each hospital.

Vascular anastomosis: the size discrepancy is also found between the renal hilus vessels and those of the recipient, so that the best locations for anastomosis should be selected on the basis of this disparity. The arterial anastomosis may be terminolateral in the aorta, in the common iliac or in the external iliac, and terminoterminal to the internal iliac. When the recipient weighs less than 20 kilogrammes we recommend making the anastomosis in the aorta and inferior vena cava 558. If they weigh from 20 kg-30kg, the recommend site is the iliac artery and common iliac vein. When the graft has a double artery, if both are separated then both anastomoses are independent, but if they are close, they will be joined in bench surgery, suturing the accessory artery to the main artery.

Abdominal wall closure: closure of the abdominal cavity after transplantation may be compromised and require delayed closure in 48 or 72hours. When the disassociation between the donor and recipient is very striking, closure of the wall may cause an increase in abdominal pressure which may collapse the inferior cava and hinder the venous return from the graft. This may progress until thrombosis occurs (compartmental syndrome). In these cases positioning a Gore-Tex sheet sutured to the edges of the wound may prevent this complication, permitting the gradual closure of the wall on subsequent days 558,559. This gradual closure of the surgical wound edges will take place under Doppler ultrasound scan monitoring.

Perioperative management: to maintain correct perfusion pressure and reduce the risk of vascular thrombosis, perioperative management should include the administration of intravenous fluids (crystalloids and/or colloids) and inotropic drugs, together with correct haemodynamic monitoring 552:

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  Monitoring central venous pressure with a central venous catheter (12-18cm H2O) and direct monitoring of arterial pressure.

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  Due to the risk of retarded graft functioning, the average arterial pressure obtained after 10minutes of graft reperfusion should not be lower than the pressure when the clamps were removed.

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  The ratio between the average arterial pressure and weight should be greater than 4.3 in patients who weigh from 13 to 21 Kg (56–90mmHg), and ideally greater than 2.5 in patients who weigh more than 22 Kg.

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  Although graft survival 5 years after LDKT from a donor over the age of 50 years is less than that of transplants from young living donors, it is better than any graft from a deceased donor, including young ones (B).

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  We suggest that living donors over the age of 50 years should be assessed on an individual basis for a paediatric recipient, as the graft survives for a shorter time, even though this survival time is longer than that of any graft from a deceased donor, including young ones (D).

A tendency has been observed in international registries over recent years for more renal transplants to be used from donors over the age of 50 years for paediatric KT 560. Although survival at 5 years is less than that corresponding to young LDKT, it is better than that of any graft from a deceased donor, including young ones 554,557,561–563. Long-term graft survival becomes poorer to the degree that donor age increases over 50 years 554,557,563.

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  Occlusive thrombosis of the inferior cava vein and mid aortic syndrome require planning of the transplantation which includes selection of the optimum donor and planning of the surgical approach, which has to be adapted to the anatomy of the recipient (D).

Of the vascular anomalies which compromise transplantation into a paediatric recipient, occlusive thrombosis of the inferior cava vein is one of the most challenging situations, and although rare, it is the most frequent such anomaly 564–566. The other complex vascular anomaly is mid aortic syndrome, which is usually progressive during infancy but tends to stabilise during puberty, so that transplantation should be delayed as far as possible or may not even be feasible. Planning a transplantation should include the selection of an optimum donor and plan the surgical approach, deciding on the best anatomical site for anastomosis based on recipient anatomy.

All KT candidates must be subjected to previous vascular evaluation by iliac-cava Doppler ultrasound scan. Those patients with a suspicion of venous thrombosis or arterial anomalies should also be subjected to other more specific imaging tests such as CT-angiography, magnetic resonance angiography or transjugular retrograde venography to permit planning of the surgery. It is also important to determine whether any risk factors for hypercoagulability are present.

In inferior cava vein thrombosis the veins which are collateral to the thrombosis should be avoided as venous graft drainage may be compromised, favouring the thrombosis. Possible vascular structure are: the ovarian vein, the left renal vein, the superior or inferior mesenteric vein, the portal vein or even deeper veins such as the lumbar veins. As the first option, and on condition that it is thrombus-free, we should use the infrahepatic cava vein, placing the graft in orthotopic position on the left side 565, performing left nephrectomy and using the native renal vein for the anastomosis to the renal vein of the graft, with anastomosis of the renal artery of the graft directly to the aorta. If the renal vein of the donor is short, a lengthening procedure may be used; either with the cava of the donor or with a segment of gonadal vein 564,565. The urethra will be re-engrafted using modified Lich-Gregoir technique if we have sufficient length, or by means of urethra-ureterostomy between the donor urethra and the native one, if the first is too short 558,559,567.

During the postoperative phase anticoagulation should be used with heparin, followed by platelet antiaggregation, as well as ensuring venous permeability by Doppler ultrasound scan immediately after the operation and magnetic resonance imaging and/or vascular tomography 3 months after the transplantation.

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  We recommend pre-transplantation urological evaluation using cystourethrography to identify anomalies and treat them before engraftation (B).

Patients with a neuropathic bladder, posterior urethral valves, complex urological malformations and urological problems associated with anorectal malformation, such as cloacal fistula are common in KT candidates. These anomalies may endanger graft survival, due basically to the vesical dysfunction which accompanies them. Pre-transplantation urological evaluation is therefore a requisite for a LDKT, allowing us to identify problems and duly treat them prior to engraftation 568. Cystourethrography will be the first test used in this evaluation.

If there is a suspicion of vesical dysfunction we will perform a urodynamic study to confirm whether the bladder is dysfunctional and identify the type of problem (hyperreflexia, low accommodation or myogenic failure). High grade urethral vesical reflux in native kidneys favours repeated post-transplantation infections and should be treated, surgically or endoscopically, before transplantation 558,559,567,568.

Correction of vesical dysfunction will require specific treatments prior to transplantation, such as the use of anticholinergic drugs and/or intermittent catheterization, the injection of botulinum toxin, vesical augmentation or continent urinary diversion.

Vesical hypoplasia or urethral agenesis and atresia require reconstruction of the urinary tract before transplantation, constructing a neobladder from a colon or ileal segment, and a Mitrofanoff-type drainage tract 564,569,570.

• •

  The time during which LDKT is contraindicated in a malign process should be evaluated jointly with Oncology depending on the type, grade and extension of the tumour (D).

There is no evidence or agreement on how long the waiting time should be before receiving a transplantation after the complete cure of a neoplasia. The most advisable strategy is currently therefore to evaluate the risk of relapse together with oncologists, according to the type, grade and spread of the malign process, deciding the necessary waiting time on an individual basis 571. Modern genetic studies are now very useful aids in distinguishing between different biological subtypes and thereby help in decision-making.

Wilms’ tumour is an exceptional case, as the transplantation candidate may be considered to be a valid recipient immediately after a complete cure, without having to wait the traditional 1 - 2 years 567.

• •

  LDKT is not contraindicated in recipients with a severe intellectual deficit, as there are no differences in graft survival between them and other patients. The final decision will be based on agreement between the transplantation team and the parents (NG).

The decision to perform a KT in a paediatric recipient with severe psychomotor retardation is always difficult, and it should be adopted by all of the members of the multidisciplinary transplantation teams and the parents, who are responsible for the patient's independence 572. Given that patient and graft survival are similar to those for other patients, the fact that a severe intellectual deficit does not contraindicate receiving a KT is perfectly valid 573. Absolute contraindications derive from the association between psychomotor retardation and other concomitant situations which in themselves are each a complete restriction 571–576.

• •

  We suggest that LDKT should be delayed in recipients with a BMI higher than 35 Kg/m2 due to the increased risk of graft loss, stimulating weight loss by means of habits that modify their lifestyle (D).

Data from the European registry indicate that Spanish children who receive KT are often overweight and obese 577, due in part to the changing Western lifestyle. Certain hereditary pathologies such as Prader-Willi or Bardet-Biedl syndromes are associated with renal failure subsidiary to replacement therapy and specific problems with obesity which have to be evaluated, defined and treated before transplantation.

Potential recipients should be assessed before transplantation in nutrition units, changing their diet and stimulating physical activity and sport. Recipients with a BMI>35 Kg/m2 are at increased risk of graft loss ten years after transplantation 578, so that they should be encouraged to lose weight. The decision to perform a KT in an obese paediatric recipient should be based on team decisions.

• •

  Although it is ideal for a paediatric recipient to receive an isogroup donation, ABO incompatible LDKT in a group O or B paediatric recipient with low isoagglutinin levels is an option that can be considered (C).

Although there is no evidence which specifically supports the paediatric indication, ABO incompatible LDKT in a group O and B paediatric recipient with low isoagglutinin levels against the potential donor, and using plasmatic exchanges, immunoabsorption or rituximab, it is a reasonable option in cases with large increases in waiting list time 579–581. In recent years it has been found that patients with low isoagglutinin titres (<16) can receive an ABO incompatible transplantation without the need for plasma exchanges 582, although there is no evidence to indicate which isoagglutinin levels permit transplantation without previous treatment 583–586.

The presence of preformed anti-HLA antibodies drastically worsens the result of KT in children as well as in adults 562,563. Although desensitization programmes give good results over the short to medium terms, the long-term prognosis is still disappointing. Several countries have developed national or international programmes with the aim of prioritizing transplantation in these patients by using a virtual crossmatch 587–591.

LDKT in highly sensitized children is no different from the situation in adults, and it would be the therapy of choice if the potential donor had no antigen prohibited by recipient antibodies. Otherwise, a child with the presence of a titre above 98% against the panel could be included in the national scheme of highly sensitized patients 591, while those patients with preformed antibodies but with a lower titre could be included in the deceased donor waiting list, while evaluating the possibility of paired LDKT or even using a specific desensitization protocol, depending on the patient's situation and how long they have spent in dialysis 592,593.

There are few absolute contraindications against performing a KT in the paediatric age 567,573–576: malign neoplasia in the previous 12 months, pulmonary disease which requires continuous oxygen therapy, irreversible heart failure, active infection, a refusal to complete the normal vaccination schedule or inappropriate social support for post-transplantation treatment.

Laparoscopic harvesting has less morbidity than open nephrectomy for the donor, and the functional results of the graft are the same (B).

Age and social aspects: 90% of living donations in childhood are made by the parents, and the factors limiting age are described in a previous section. The selection of one or the other parent if they are equally compatible and healthy is their own choice after they have been informed of their level of compatibility. All of the psychosocial and economic factors which influence donation should also be taken into account 594. In living donation for a paediatric recipient other family donors or donors with emotional ties are also accepted: compatibility must be taken into account, and the advantages must be weighed in comparison with a deceased donor transplantation 563,593. Although donation by a young sibling (under the age of 25 years) is not contraindicated, this requires a far more exhaustive evaluation to prove their maturity. Sometimes we find single-parent families without any social support, and these situations would lead us to advise against LDKT. In any case, it is fundamental to offer psychological support before and after donation, and although LDKT may strengthen positive emotions between the donor and recipient, it may also lead to tensions and anxiety, above all in adolescent recipients 594.

Aspects of surgery and the harvesting: the main limitation of LDKT for paediatric recipients is the size discrepancy between donor and recipient vessels. To guarantee a suitable flow to the kidney the recipient artery for the anastomosis should be twice the width of the renal artery of the donor, or at the least the same size 595. In children who weigh less than 15 kilogrammes it is often necessary to wait for a time before being able to perform the transplant with assurance of success. The presence of vascular anomalies or multiple pedicles increases the risk of graft thrombosis; thus when there is a double artery and it is close to the main artery, the accessory artery anastomosis to the main one should be terminolateral, with a single anastomosis in the recipient. If both arteries are a certain distance apart it will be necessary to make the anastomoses separately. There is no established limit on the maximum number of arteries over which a kidney should be rejected. The surgeon's criterion and experience will decide if a transplant is possible. Renal angiotomography reconstruction in three dimensions, including the excretory phase, is the method of choice for evaluation of the arterial and venous anatomy and the parenchymal and collector system of a potential living donor 596.

The left kidney is usually collected, as if they are both equally suitable this usually facilitates the vascular anastomoses, while otherwise the rule is that the best kidney should be left in the donor. Laparoscopic nephrectomy is preferred over open surgery for renal harvesting from a living donor 597, as it causes less donor morbidity and has similar functional results. The greatest problem is that it is harder to obtain renal vessels of an appropriate length, above all the renal vein, and this occurs more often with the right kidney. A hand-assisted laparoscopic approach improves traction on the kidney and obtains a more suitable vessel length. Positioning the graft inverted in the recipient may also facilitate the vascular anastomoses in a graft with short vessels.

• •

  We suggest that transplantation candidates with more than 80%-85% of cPRA antibodies against potential donors should be considered sensitized (Quality of evidence: C).

• •

  We suggest that LDKT candidates and their donors should be informed of the different options for HLA-incompatible transplantation (paired, desensitization or specific lists with preference for a deceased donor) (C).

• •

  The decision to perform an HLA-incompatible transplantation by using a desensitization protocol should be considered depending on the characteristics of the recipient, the donor and time in the waiting list, in comparison with the increased risk of antibody-mediated acute rejection and other complications due to over-immunosuppression. (NG).

• •

  We recommend a desensitization protocol which includes rituximab, IVIG and apheresis techniques (immunoadsorption or plasma exchange) (B).

• •

  We recommend adding anti-CD20, as it increases the probability of accessing a transplantation (A).

• •

  We do not recommend substituting rituximab with bortezomib, due to its toxicity and poorer results (B).

• •

  As there are no studies which compare different IVIG preparations (non-specific or CMV hyperimmune) it is not possible to recommend one or the other (NG).

• •

  The inclusion of eculizumab in the usual desensitization protocols reduces the incidence of short-term antibody-mediated acute rejection (B).

• •

  Imlifidase makes it possible to transform a highly positive crossmatch tests into a negative one in 6hours (C).

• •

  We suggest that LDKT HLA-incompatible candidates who are not suitable for desensitization should be included in specific deceased donor transplant lists for highly sensitized candidates (C).

1.1.1 Desensitization protocol

Desensitization consists of removing pre-existing antibodies from the body using apheresis techniques, blocking existing ones or their actions by using IVIG, preventing the formation of new ones by blocking B-cell proliferation and preventing recognition and an immune response by means of immunosuppressant therapy. There are several desensitization protocols, and in general they are based on the use of rituximab, IVIG and apheresis techniques (2,611) New drugs have been added in recent years, including eculizumab and imlifidase, and these reduce the incidence of acute rejection. A conditioning regime is shown in Figure 13.a) B-cell depletion agents

Figure 13.

The most widespread form of desensitization. Rituximab commences 31 days before the planned date for transplantation. From 7 to 14 days before transplantation the patient is admitted to hospital and PPHS or IA commences until the crossmatch is negative. 100mg/kg of CMV specific Igs is infused after each session of PPHS/IA. Immunosuppression also commences with tacrolimus, mycophenolic acid derivates and prednisone. Prophylaxis is given after transplantation, with valganciclovir, septrin, itraconazole or inhaled amphotericin. Basiliximab or thymoglobulin is given for induction, and PPHS takes place on days +3,+5 and +8. (Ref: 614).

(0.35MB).

The most widely used regime at the present time consists of using rituximab for one month prior to commencing apheresis. It functions 2-3 after infusion, with a peak at from 2 to 4 weeks, and this effect may be maintained for up to 12 months 612. The dose used in the majority of protocols is 375mg/m2 body surface, and premedication with paracetamol, steroids and antihistamines to prevent adverse secondary reactions. Some authors use bortezomib, a plasma-cell depletion agent, with different results 611, although with a high incidence of side effects 613.b) Immunosuppression

Immunosuppression starts one or two weeks prior to transplantation, with tacrolimus (0.15mg/kg to achieve levels of 8-12ng/ml in the first month), MMF at a dose of 1g every 12hours or 720mg every 12hours of MPHS and 20mg/day prednisone 614.c) Apheresis

In patients with no vascular access (pre-dialysis or peritoneal), it is necessary to catheterize a central vein (preferably the internal jugular vein) 615 for apheresis with or without dialysis. If the technique of centrifugal plasma exchange is used then this can be applied using a peripheral vein. The apheresis techniques used are PPF or plasma exchange, double filtration PPF and immunoadsorption (IA). The advantage of IA over PPF is that it does not remove plasma, so that plasma proteins including albumin and coagulation factors are not lost in the exchange, so that replacement is not required, as it is with PPF 616. The drawback is that it filters IgG 3 less efficiently and it is also more expensive; both techniques are usually combined 617. The volume of plasma used in the exchange tends to vary at from 1 to 2.5 volumes per session, while the number of sessions varies and generally depends on the degree to which the patient is sensitized. When the crossmatch tests with the donor for CDC and CF are negative and the NFI of the donor-specific antibody or antibodies falls below 1000 the patient is considered to be desensitized and transplantation takes place 614,618.d) Immunoglobulins

After each apheresis session in which some antibodies have been removed, IVIG is administered with the aim of neutralising the antibodies and modulating the immune response 619. IVIG reduces the incidence of acute rejection and graft loss in sensitized patients 620,621. Two versions are marketed, non-specific IVIG and hyperimmune IVIG CMV. There are no studies which compare the efficacy of both versions. One study compared historical series of candidates treated with high doses of IVIG or low doses plus PPF, and the results of the latter group with PPF were better 622. Non-specific IVIG is used in doses of 500mg/kg weight - 2000mg/kg weight 623, with a maximum dose of 150g, and a larger volume is required for administration. Anti-ABO isoagglutinins are usually included in its presentations, and premedication is required to prevent adverse reactions 624. CMV-specific IVIG is used in a 100mg/kg dose 625–627, so that the volume administered is considerably smaller. It is highly purified and has CMV and Epstein Barr virus neutralising antibodies, so that it may offer beneficial results in terms of the short-term prevention of opportunistic infections 628. In economic terms the results seem to favour using non-specific IVIG, although no cost-effectiveness studies have been performed.e) Eculizumab

Eculizumab is a humanized monoclonal antibody against the C5 fraction of the complement, preventing it from cleaving and blocking the opsonizing and inflammatory capacity of C5a and the formation of membrane attack complex C5b-9 629. Use of Eculizumab during 4- 9 weeks is associated with a reduction in the incidence of antibody-mediated acute rejection 630,631, although an increase in the MFI of the DSA has been detected, together with a higher frequency of transplantation glomerulopathy. This drug is tolerated well, although patients have to be vaccinated beforehand against meningococcus, pneumococcus and haemophilus.f) Imlifidase.

Imlifidase (endopeptidase) is a drug collected from Streptococcus pyogenes, and it functions like scissors, cutting the bonds which join the different chains of the immunoglobulins, turning a positive crossmatch test into a negative one in 6hours. Data from the first international studies show that it is possible to transplant into sensitized patients with a reduced incidence of rejection in comparison with the usual protocols 632,633.g) Others.

Tocilizumab is a monoclonal antibody against the IL-6 receptor, and in initial studies it improved the results in comparison with previously used desensitization protocols, although we do not have enough information about its use in clinical practice 634.

Other drugs are under development 635, and these may improve current results. These drugs include the administration of a complement C1 fraction inhibitor (C1Inh) although it is still in phase I/II 636.h) Induction

Once successful desensitization is considered to have been achieved then the transplantation takes place. Induction therapy with basiliximab or thymoglobulin is administered, depending on the protocol and groups 614. Some protocols include the use of alemtuzumab instead of thymoglobulin 623,637.i) Prophylaxis

The aim of desensitization protocols is to reduce the immune response, so that opportunist infections may increase. In spite of this the prophylaxis does not differ very much from what is used in transplantations without desensitization: cotrimoxazol during 3-6 months and valganciclovir during from 3 to 6 months, basically in seropositive donors and CMV seronegative recipients. Antifungal prophylaxis will follow local practice; some hospitals use oral itraconazole or inhaled amphotericin during 3-4 months 614.

Patients who receive eculizumab should be vaccinated against meningococcus, haemophilus and pneumococcus, and they should receive oral penicillin until at least one month after treatment has ended, as recommended for patients with aHUS 638,639.

A retrospective multicentre study of hospitals in the U.S.A. found that the results in terms of transplanted patient survival after desensitization are better than those corresponding to patients who remain in dialysis before transplantation, and those who remain in dialysis and do not receive a transplantation 640. Other studies do not find these differences between the groups of those who were transplanted or in the waiting list 604. This may be explained by differences in definitions, desensitization, the method used to select the control group, the population and mortality in dialysis, which is higher in the U.S.A. than it is in Europe 49. In waiting list patients with high cPRA, this is an independent risk factor for mortality in transplantation candidates 641,642.

The probability of accessing transplantation after desensitization varies from 37% to 96%, depending on the protocol used, the level of sensitization and group experience 611,614,622,623,630,643–649. A review found that the probability of transplant was 90.7% when PPF was used, 95.5% when IA was used, 73% with the use of high dose IVIG without apheresis and 30.8% with bortezomib 611. The most experienced group with desensitization is probably the Cedairs Sinai group, Los Angeles. Vo et al. have transplanted 45/56 (80%) of the waiting list patients with PRA >80% with a living donor using desensitization, as opposed to only 2% per year in the waiting list without desensitization. They were unable to transplant 9/56 (16%) of the candidates 623. There is little information on the frequency of transplantation in patients where desensitization had failed.

When bortezomib is used, the probability of transplantation varies from 43% to 84% 613,650,651. It was necessary to suspend bortezomib due to adverse effects associated with bortezomib in 11.5% of patients, and in 15.4% without association with bortezomib.

In successive series patient survival is higher than 90% at 1-5 years and 80% at 8 years, while graft survival is higher than 90% at one year and from 60%-70% at 5-8 years, in spite of high acute rejection rates 611,614,618,623,630,637,643,646,652–655.

Recent publications show the results of using endopeptidases (Imlifidase) in 46 patients, the majority with a deceased donor (n=39), although patients who had received a LDKT were also included (n=7). 85% of patients had a positive crossmatch test, DSA in 93% of cases and cPRA >97%. The protocol also includes the use of rituximab and IVIG. Patient and graft survival are 100% and 96% at the 6th month, respectively, with a 27% incidence of antibody-mediated rejection 632,633. Adding eculizumab to the usual desensitization protocol makes it possible to reduce this rejection rate to 12%-15% in the first year, with renal survival higher than 90% 630,654.

In an experience of the Mayo Clinic in patients with DSA MFI >1000 and negative CF, 75% with LDKT, shows a 0% incidence of antibody-mediated rejection. The incidence of chronic antibody-mediated rejection was 17% and patient survival was 96.3%, while graft survival (death censored) was 86% after an average follow-up of 4 years 637. These patients were not subjected to desensitization, so that the authors consider that certain patients could benefit from a transplantation, especially one from a living donor, rather than remaining in the waiting list for a donor with a completely negative crossmatch test (negative DSA, MFI<1000).

It is possible to apply desensitization protocols in deceased donor KT with IA in the immediate postoperative period. If the crossmatch test was positive pre-IA but negative post-IA, the patient was transplanted. 101 patients were transplanted with this protocol, 27 of them were CDC positive pre-IA and negative post-IA. The incidence of antibody-mediated rejection stood at 41%. Death censored renal survival was worse in the patients with DSA than in the controls without DSA 656.

Some authors have reported the results of a combination of desensitization and paired LDKT, with a small number of patients, although they were able to transplant candidates with 100% cPRA 657,658.

Table 12 shows a summary of the latest publications on the results of desensitization.

• •

  Desensitization protocols may expose patients to a higher incidence of infections and other adverse effects (NG).

• •

  The costs of HLA-incompatible LDKT are higher than those for a HLA-compatible donor, although it is cost-effective in comparison with remaining in dialysis (NG).

The number of infectious complications (CMV, BK, urinary infection) is slightly higher in the group of sensitized patients than it is in those who are not sensitized. Few data exist on the incidence of EBV, and it is even possible that IVIG has a protective effect 603,614,632,640,643,646,655,659–664 (Table 13).

Other complications have been reported in connection with desensitization protocols that are especially linked to the use of apheresis techniques and other medications 639.

HLA-incompatible LDKT is more expensive than a compatible KT, due to the use of B cell depletion agents, apheresis, IVIG, induction, immunosuppressant medication and the time spent in hospital 665. Although its total cost is higher, LDKT is cost-effective in comparison with remaining in dialysis 623,666. The costs of additional medication such as eculizumab have not been evaluated.

• •

  We recommend ABOi LDKT as it gives results that are comparable to those achieved by ABOc LDKT (Quality of evidence: B).

• •

  We suggest that the option of ABOi transplantation should be considered in hospitals that perform LDKT to increase the opportunities for transplantation (NG).

The rule that donation should be avoided in case of blood group incompatibility has been abandoned and successfully surpassed 670. Poor initial results 671 meant that this option was side-lined until the 1990s, when different groups, especially in Japan 672,673 reported excellent results in series with a large number of patients. This led to its use by groups in the U.S.A. 674,675, France 676 and Sweden 677,678. In Spain the first ABOi LDKT took place in 2006, in the Hospital Clínic, Barcelona, and the good initial results were confirmed by other groups 679–683. The Hospital Universitario in A Coruña 684 soon tried this option, followed by several other hospitals 685.

• •

  We suggest that ABOi transplantation should be considered an alternative when there is no ABO-compatible donor (D).

• •

  We suggest monitoring titres of the IgG and IgM isoagglutinins. The importance of the role of both types of immunoglobulin in transplantation is controversial (D).

The initial acceptance criteria are the same as for an ABOc LDKT (9), to which we add the possibility of determining antibodies against A or B incompatible antibodies, known as isoagglutinins. The titre of IgG and IgM isoagglutinins should be the same or less than 1/8 for transplantation to take place. The next requirement will therefore be to apply one of the apheresis treatments used to reduce the isoagglutinin concentration, if necessary (it always is necessary, except for very low basal titres <1/8). Normally from 3 to 5 apheresis sessions are required to reduce the titres to a safe level for transplantation. If the basal titres are very high (>1/512) this increases the risk that the apheresis treatment will not achieve an effective reduction in the same, so that donation is ruled out. This gives rise to an enormous economical and emotional cost 686,689, so that many hospitals recommend or contraindicate desensitization treatment when the basal titres are very high (9,686,687). There is no agreement on whether a low titre is simultaneously necessary for both Immunoglobulins (IgM and IgG) 690,691, or if this is necessary for only one of them. Some groups believe that it is crucial to reduce the IgG titre, while others hold the contrary opinion. On the other hand, highly experienced hospitals accept transplanting patients with higher titres (1/32) at the moment of KT 692,693.

When the incompatible blood group of the donor is A2, given the low antigen expressivity some hospitals do not formally consider this to be an ABO incompatibility if the titres are low, and they go on to transplant directly as if the donor were ABO-compatible 694.

This aspect is described in detail in section 9.

Desensitization for an ABOi KT requires two essential actions: eliminate isoagglutinins from the circulation and inhibit their synthesis. The treatment can be complemented with the administration of IVIG, which may have an immunomodulating effect, as well as making it possible to restore the protective antibodies lost in apheresis. Nevertheless, these preparations also contain isoagglutinins, which may be a confusion factor when interpreting how titres evolve during treatment 686,695.

To centre on the different apheresis techniques, many different forms have emerged in recent years (53,683,696-701). Basically there are three techniques, each with its own versions: plasma exchange, specific immunoadsorption and non-specific immunoadsorption. When we are dealing with low titres, any technique will be effective. To effectively reduce high titres, no technique has been proven to be any more effective than the others, although some authors state that specific immunoadsorption would be the best. Economic costs should be taken into account as well as efficacy, together with logistic aspects and side effects, especially in connection alterations in coagulation factors, reactions of intolerance the risk of infections 688,698,699. The immunoadsorption techniques are tolerated the best, making it possible to treat a greater volume of plasma in each session without altering the coagulation factors. An interesting logistic aspect is the possibility of simultaneously carrying out haemodialysis and apheresis.

Respecting the blocking of isoagglutinin production, splenectomy was used in the first Japanese experiences 671,672. The chief drawback with this, apart from possible surgical and complications and infections, was the need for routine vaccination against encapsulated bacteria over an indefinite period of time. Replacing splenectomy with treatment using rituximab not only proved to be more effective and safer, as its effect reduces after a few months. Although it is not supported by any clinical trials, it is now the treatment of choice 676,678,682,684,697,698,702–704. However, there is no agreement on the number or size of doses, how many days it should commence before the start of desensitization or other aspects of administration criteria. Some groups consider a single dose given 3-4 weeks prior to transplantation to be sufficient; others prefer two doses, the first 3-4 weeks before transplantation and the second immediately beforehand, seeking to combine the immediate and deferred pharmacological effects 678,682,684,692. Opinions also differ regarding the size of the dose. At first the same dose as the one used in lymphoma treatment was given, 375mg/m2 once or twice 473, but after studies were published indicating that a lower dose was enough to remove CD19-positive B lymphocytes from circulation guidelines were established that varied from 50mg to 400mg 678,705–707. Several meta-analyses associate the excessively prolonged use of this drug (but not the size of the dose) with higher mortality due to infections 697,698,700,701,708,709. Thus these findings and the improved efficiency of apheresis techniques have led some groups to decide against systematically administering rituximab, and they now only give it in certain cases 710,711.

Bortezomid would be included among the other therapeutic options for blocking isoagglutinin synthesis. It has been trialled as a desensitization therapy in ABOi LDKT in cases refractory to rituximab or to substitute it 680,712. Eculizumab has also been trialled for usefulness, and it was able to prevent antibody-mediated rejection in four patients with no apheresis treatment 713,714. There is interest in knowing the possible efficacy of Imlifidase, which is capable of cleaving all circulating IgG in two steps and a few minutes after single dose. A limiting factor would be its lack of efficacy against IgM antibodies.

Finally, many hospitals routinely use IVIG. This would have two uses: it restores the immunoglobulins eliminated by apheresis, for which administration at low doses of 100mg/kg - 200mg/kg would be sufficient, or it could be given at high doses (1g/kg - 2g/kg) to achieve a multifactorial immunomodulating effect, most especially providing anti-idiotype antibodies which would facilitate the phenomenon of accommodation 715. Three factors arise against the systematic use of IVIG: it is unnecessary to replace idiotype antibodies when specific IA is used; its efficacy has yet to be proven, so that it may constitute an unnecessary cost, and finally its isoagglutinin content may distort the results of titration 677,682,683,690,695.

How do the isoagglutinins behave after transplantation? Is it correct to monitor titres and no intervene while they remain low?

• •

  We suggest practicing one or two apheresis sessions after transplantation as the protocol, although as no clear recommendations exist, other groups prefer to wait for a possible rise in the titres (C).

Isoagglutinins must be at a safe level before practicing an ABOi LDKT. Anti-A or B antibodies may bounce back after transplantation to levels even higher than they were at the start of desensitization therapy 687,706. This potential rebound may lead to an early rejection, although in the majority of cases when an increase in titres is detected without any alteration in graft functioning, biopsy of the same shows the absence of immunological damage except for the usual presence of C4d deposits 716,717. A low level of isoagglutinins in the peripheral blood may indicate that most of them have been absorbed by the graft, so that circulating anti-A or B antibodies would have less avidity for donor antigens, reducing their pathological involvement 718.

In any case, after transplantation some groups believe it to be necessary to recommence apheresis sessions if the isoagglutinin titres increase during the first two weeks. Other groups only do this if there is renal dysfunctioning or a biopsy shows signs of rejection other than C4d deposits. Some hospitals prefer to include one or two apheresis sessions in their protocol, in the attempt to prevent a rebound in the titres or even to prevent antibody-mediated rejection. It should not be forgotten that this rejection may arise even if the patient has not yet shown a rise in titres 680–682. On the contrary, other hospitals consider that post-transplantation apheresis sessions only cause problems (with haemorrhaging, logistical problems and unnecessary expense) without any benefits 672,684,698,719.

Is patient and graft survival the same as with ABOc LDKT?

The published results of series of hospitals report similar results or slight differences in patient and graft survival (C).

• •

  Meta-analyses or analyses of registries are able to detect poorer patient and graft survival due to infections in the first year of evolution (B).

• •

  We recommend closely monitoring complications with infections in ABOi recipients due to certain experiences that have reported increases in mortality secondary to infections (B).

The meta-analyses that report the results of patient survival after receiving an ABOi LDKT do so by comparing this with the results of ABOc transplantation. The majority show that there are no differences, or that any differences are small 53,696,697,703,704 and that they disappear over the long-term. Even when the potential increased risk of complications due to infection caused by desensitization therapy is taken into account, ABOi LDKT would be better in any case than deceased donor KT or remaining in dialysis 720. On the other hand, nor was it found to have higher mortality when it was compared to paired donation 721.

In terms of graft survival, many groups have reported similar results over the short to medium term and even over the long-term 682,692,693,700,708,722. Other series found poorer results, and data from meta-analyses and registry studies underline shorter graft survival than in ABOc LDKT at one, 3 and 5 years, although there were no long-term differences 53,697,703,704,722.

Although ABOi transplantation is considered to be a reasonably safe procedure, the use of powerful immunosuppressant drugs, and especially rituximab, is associated with increased infections 700,708,709. Several series report a higher frequency of viral infections 723,724 as well as pneumonia, urinary infections and infections of the surgical wound 724,725. Not all of the series agree with these findings, and moderating the use of rituximab as suggested by Japanese groups has been accompanied by a significant fall in infection by CMV 693. Moreover, with this moderation and other anti-infection prophylactic measures, rates of urinary infection and pneumonia have recently been reported that are comparable with those corresponding to ABOc transplantation 698,723.

Unlike infections, the incidence of tumours does not seem to increase in ABOi transplantations, although it is true that there is not so much literature on this subject 726,727.

What occurs with acute rejection?

• •

  The incidence of acute rejection, and particularly antibody-mediated acute rejection, is higher in meta-analyses of ABOi transplantations, although many hospitals report comparable results (B).

The initial Japanese series reported a significant incidence of graft loss due to hyperacute or accelerated rejection, and in fact this may be the main or perhaps the only difference between ABOi and ABOc transplantations. This would be due to the swift development of acute rejection mediated by antibodies against A or B incompatible antigens. On the contrary, the initial Swedish series described a very low rejection rate, cellular as well as humoral, which it attributed to the important amount of immunosuppressant medication administered. Other works underline a higher incidence of mild cellular rejection 679,728,729.

Accommodation and rejection mechanisms

A phenomenon involving possible immunological accommodation in a situation of ABO incompatibility arises in almost all ABOi transplantations: the presence of high titres of isoagglutinins, AB antigen expression in the endothelium and C4d positivity in peritubular capillaries, in the absence of other signs of rejection and with conserved renal function (B).

• •

  Early losses due to accelerated rejection are rare and are usually accompanied by thrombotic microangiopathy (C).

• •

  We suggest that prophylactic anticoagulation should be administered in the first weeks after transplantation, due to the susceptibility of the ABOi endothelium to thrombotic phenomena in the case of any immunological or non-immunological insult (C).

The most intriguing aspect of rejection mediated by antibodies against ABO antigens is that it rarely appears after 2 - 3 weeks post-transplantation, in spite of isoagglutinins being detected, even at high titres, and signs in protocol biopsies that the complement had activated. Several different mechanisms may intervene in accommodation, and they may affect antibody synthesis, exposure to antigens and the development of active protection measures. To establish accommodation it is necessary to overcome the first phase successfully, in which the complement together with the initial damage caused by the antibodies would activate a repair and protection response against the cytotoxicity which over the long-term will favour the acquisition of activate cellular and tissue protection mechanisms 64. If in the first phase ultrastructural alteration of the plasma membrane had occurred, with regional changes in platelet aggregation and neutrophil recruitment, this intrinsic resistance against cytotoxicity would be lost and graft thrombosis could occur in the first hours 718. It is therefore recommended to administer prophylactic anticoagulation during the first week.

What role would the complement and C4d deposit in transplant biopsy?

The systematic presence of C4d in protocol biopsy stains in ABOi transplantations is well-known, although its exact significance is not known, although it tends to be understood as an accommodation phenomenon 713,730,731. Patients with an ABOi transplantation with C4d deposit but no other histological abnormalities do not usually develop glomerulopathy of the transplant or chronic graft dysfunction. In fact, when they have a persistent diffuse C4d deposit they have less chronic damage after the first year. Pharmacological blockage of complement activation may be of interest to prevent or treat humoral rejection, as well as to prevent thrombotic microangiopathy phenomena associated with endothelial damage. There are few experiences, which nevertheless were successful, in the prophylactic use of eculizumab in transplantations of this type.

• •

  We recommend the option of paired KT over HLA-incompatible transplantation due to the improved survival it achieves, so that this information should be given to paired with HLA incompatibility (Quality of evidence: B).

• •

  Patients with very few transplantation options (blood group O and highly sensitized) should receive an explanation of the possibility of adding treatments such as desensitization to paired KT cruzado, to increase their possibilities of transplantation (NG).

The main aim of the Spanish paired transplantation 543 is to increase the possibilities of LDKT in those cases without donor-recipient compatibility, due to ABOi blood group or a positive crossmatch test, as well as other circumstances in which, although transplantation within the pair is not impossible, there is a real benefit associated with a paired KT procedure (such as a reduced difference in donor-recipient age or donor anthropometric characteristics that better fit the needs of the recipient).

The regulation which established the procedure for paired transplantations was developed and published by the ONT in 2009, in collaboration with a multidisciplinary committee of experts in different aspects of the living donor KT procedure: nephrologists, immunologists, urologists, transplantation coordinators and experts in bioethics and lawyers.

Once the scheme was under way a continuous improvement mechanism was established, based on the creation of a workgroup and a scientific committee (whose members are drawn from the workgroup). The workgroup is composed of the individuals in charge of the scheme in the ONT and in each participating hospital. It is convened by the ONT once a year to analyse the results of the scheme and establish modifications in different areas to achieve continuous improvement. The functions of the scientific committee include evaluating complex cases, as well as drawing up suggestions for improvements.

The scheme has thereby gradually improved, by including new hospitals, unifying clinical and immunological criteria, updating registry information, expanding donor typing, including chains of altruistic donors, creating a compatibility algorithm, the recent inclusion of the possibility of performing ABOi transplantation in the scheme for potential recipients with HLA sensitization, the priority score, the search for renal transport schemes which reduce times and are sustainable, and the broadening of pairs and HLA diversity by making the scheme international. In fact, three international paired transplantations have now been performed, between Spain and Italy and between Spain and Portugal 748.

The scheme contains 3 elements: the requisites which transplanting hospitals have to fulfil to take part, the computing tool which contains the donor and recipient database, a selection algorithm for possible exchanges, and a tool for optimising detected cycles, to maximise the number of transplantations and increase the options for recipients who are “hard to match”, and a working protocol which describes the procedures for registering pairs, creating pairs (or matching-run) and the procedure which leads to transplantation.

An exchange of donors between donor-recipient pairs previously registered in a database, to form cycles of two and three KT.

Figure 14.

Exchange options in the Spanish paired kidney transplantation scheme.

(0.15MB).

The donors and recipients in these cycles form new pairs which are “more” compatible in immunological terms or, if they were compatible beforehand, ones who are more suitable in anthropometric terms or age. Thus for a cycle to be formed it has to be bidirectional. That is, all of the donors in the cycle should be compatible with the recipient selected for them. It is a legal imperative that the members of the new pairs must not know each other 41.

The transplantation procedures are executed simultaneously, to minimise the risk of one or several recipients not receiving a transplant after the nephrectomy of their incompatible donor.

The inclusion of an altruistic donor in the scheme, thereby commencing a KT chain. Compatibility in this option is one way, that is, it is only necessary for the donor to be compatible with the next recipient in the chain, facilitating the creation of the latter 749.

In this case it is not necessary to carry out all of the transplantations at the same time, as if an unexpected event occurs which causes a recipient in the chain to not receive their corresponding KT, their donor will still not have made their donation. Being able to create the transplantation chain in several phases also makes it possible to add links, increasing the number of transplantations. This option is known as a transplantation chain with a bridging donor. The final link in the chain is a patient in the waiting list of the hospital which evaluated the altruistic donor 750.

Given that transplantation chains are characterized and differentiated by including an altruistic (Good Samaritan) donor, they are described in a specific chapter.

Hospitals that wish to take part in a paired KT scheme must have the necessary infrastructure and the agreement of all the clinical departments involved to fulfil the conditions of the scheme. The transplantation teams must also have experience in the LDKT procedure. This point is of vital importance, as donors will be exchanged between different hospitals and there must be trust in how all of them will work.

Due to the above reasons, the national paired renal donation protocol sets the following requisites:

There is a criterion which sets the minimum amount of activity. This currently stands at having carried out 15 LDKT in the three years prior to joining the scheme.

Minimally invasive techniques must be used for nephrectomy 32.

The conditions set by the scheme for carrying out diagnostic tests (such as broadening donor typing) must be accepted.

An individual in charge of the scheme must be designated at hospital level.

Participation in the scheme must be approved by the corresponding health authority 543.

The scheme currently has 26 participating hospitals and 19 histocompatibility laboratories (one of which is the reference laboratory for two Madrid laboratories and 6 others in Catalonia) in 12 autonomous communities. This is an important datum, given that countries such as the Netherlands base some of the success of their scheme on the existence of a central histocompatibility laboratory 751. In spite of the increased difficulty of managing immunologically complex patients in different laboratories, Spain has obtained excellent results. The English scheme is organized in a similar way to the one in Spain, with 20 different histocompatibility laboratories and 23 transplanting hospitals, and the United Kingdom scheme is now one which has performed the highest number of paired KT in Europe 51.

Hospitals which are not members of the scheme may include donor-recipient pairs through hospitals which are members. Autonomous Community Transplantation Coordinators establish agreements and procedures for this 543.

Thus all renal patients with a potential incompatible donor (or a compatible one, but who could benefit from an exchange) will therefore have the opportunity of taking part in the programme, thereby guaranteeing fair access to it. This opportunity for patients and their potential donors involves the right which all of them have to be properly informed about the paired LDKT Scheme 2,9.

This online application can only be accessed by hospitals which are members of the scheme and the personnel in charge of the scheme in the ONT, by entering their user name and password, to comply with the data protection law. The search for possible exchanges may be carried out manually, although the number of pairs and their complexity makes it recommendable to use the system automatically to gain good results. This computer tool includes 543,752,753:

A database of donor-recipient pairs, where the demographic and clinical data of the patients and their possible donors are registered and kept updated, as required for matching:

A patient may be registered with more than one donor. A recipients may form a pair for exchange with as many donors as they supply, which increases their chances of finding a match 752,754. From 2009 to 2018 656 donor-recipient pairs joined the Spanish scheme for paired renal donation (557 recipients with a donor, 36 recipients with two donors and 9 patients with more than two donors).

There is no upper or lower age limit for the inclusion of a recipient. The donor has to comply with the requisites established by Spanish law respecting minimum age (≥18 years) and there is no upper age limit, on condition that the donor has been considered to be suitable by the participating hospital. The donors and recipients registered in the scheme have a similar average age, at 50 years and 46.3 years, respectively.

The scheme permits patients to register with their potential a priori biologically compatible and incompatible donors, although they must also wish to make an exchange, to find a younger donor, or one of a more suitable size, improve HLA compatibility or for simply altruistic reasons 755,756. The reasons for inclusion in the scheme were ABOi in 43% of cases, the presence of DSA in 51%, ABO and HLA incompatibility in 4% and 12 pairs were compatible, amounting to 2% of the registered pairs.

The database permits the registration of altruistic donors to build a transplantation chain 51.

The application automatically associates a numerical code with each registered donor and patient, which will allow the members of the new pairs formed to remain anonymous, without the process losing traceability.

It contains a compatibility algorithm, which searches for all of the possible options for exchange within the donor-recipient pool, forming cycles of 2 or 3 transplantations and chains which commence with an altruistic donor. There are two rules:

ABO compatibility and HLA compatibility: using a virtual crossmatch test, it selects those recipients who do not have preformed antibodies against the different HLA antigens of the donor (for class I HLA as well as class II) 736,740,746.

Exclusively HLA compatibility, in this case permitting ABOi KT 697,757.

A selection tool for the detected cycles to maximise the number of transplantations and increase the options of the recipients who have most difficulties in finding a compatible donor, such as those with group O and/or highly sensitized patients 543. To this end the system has:

A score which takes into account level of immunization (cPRA), blood group, time in dialysis, donor and recipient age, the length of time a recipient has been included in the scheme and, in case of a draw, geographical distribution. Given the exceptional nature of a compatible pair and that this increases the options for transplantation, these are given priority 51.

An optimization model, which attempts to maximize:

The number of transplantations carried out.

Transplantations into patients with difficulties to find a compatible donor.

The cycles selected, which involves obtaining more two-transplantation cycles than it does those with three transplantations (on condition that the total number of transplantations is maximized)

The number of robust cycles. When cycles involving three transplantation cycles are selected, if we have to choose between two cycles that share one or two pairs and have the same score, the one that can be shortened to a two-transplant cycle will always be selected (which facilitates its eventual execution) 752.

The compatibility algorithm and the selection tool are always applied together, seeking an optimum set of possible combinations. Two programming models are currently used in Europe for this 752:

Construction of a compatibility graph, assigning as score (known as weight) to each one of the members of a pair, based on criteria set by the programme (age and level of immunization, etc.) This is the model used by the Spanish scheme.

Formulation of the different exchanges using integral programming.

Before including donor-recipient pairs in the paired transplantation scheme and continuing with the pairing dynamic, the pairs have to be informed of how the scheme works and other aspects of it.

Once the possible combinations have been selected the ONT issues a report on the results for the hospitals which are involved, using a secure information exchange space. After this moment the individuals in charge of each one of the cycles at hospital level will evaluate the information received (age, blood group and HLA typing), sharing the clinical reports of the donors and agreeing on the execution of crossmatch tests with immunology laboratories.

A 7 day deadline is set for sharing the clinical reports, plus 15 days more to carry out the crossmatch test. As a general rule, this test will take place in the histocompatibility laboratory of the hospital which registered the recipient, so that the donor and recipient hospital laboratories will agree on a date and means of sending the samples. This test will be take the form of complement mediated cytotoxicity and/or flow cytometry.

Some patients are immunized to such a high level that it is improbable that they will find a donor for whom they lack DSA. In these cases a combined strategy of desensitization and paired transplantation may be used. That is, the transplantation team may, after considering this with the immunology department and agreeing it with the recipient, decide not to register in the database the DSA which the patient has at low titres. If they are selected for exchange with a compatible donor who has one or several of the unregistered DSA in the application, then desensitization and transplantation may take place. 55,761,762.

If the results of the crossmatch tests in the same cycle are negative, the hospitals will share angiotomography images of the renal anatomy of the donors and agree the date for transplantation.

As is the case in any directed LDKT, the ethics committee should evaluate the procedure, and the donors will have to give their express consent to donation before the examining magistrate of the court corresponding to the town in which the nephrectomy or transplantation will take place 41.

In the 9 years this scheme has been working, in Spain a total of 29 rounds of paired transplantations and 203 transplantations have been carried out, distributed in 42 cycles of 2 transplantations, 27 cycles of 3 transplantations and 14 chains of transplantations that commenced with an altruistic donor 763 (Figure 15). 32.8% of the patients were transplanted in this scheme, unequally distributed according to donor and recipient blood group. The highest probability corresponded to those pairs in which the donor was group B and the recipient was group A (Table 15). Altruistic donation made 43 transplantations possible, so that without this, the rate of transplantations within the scheme would have been 26.1%.

Figure 15.

Number of 2 transplantation rounds, 3 transplantation rounds and chains initiated by an altruistic donor. Spain 2019-2021 763.

(0.17MB).

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  We recommend performing donor nephrectomy in their own hospital and transporting the kidney to the recipient's hospital for transplantation (B).

Although the scheme includes the possibility of the donor travelling to the hospital where the recipient of their kidney will receive it, the recommended option is for nephrectomy to take place in the donor's hospital and for the kidney to be transported. Nephrectomy in their own hospital permits the donor to be in contact with their family and allows them to remain in known surroundings, being cared for by the professionals who have studied them, all of which reduces the stress for the donor and their family. Moreover, if the donor does not travel to the hospital where the recipient is, it will be easier to maintain their anonymity. In Spain, 97% of paired transplantations have involved transporting the kidney (using an ambulance for this, or a high-speed train or aircraft) with an average time in cold ischemia of 5.6 (2.8) hours.

Although renal transport necessarily involves the kidneys being transplanted after a time in cold ischemia, it has been found that cold ischemia times <12hrs. do not affect the incidence of retarded renal function or graft and patient survival over the mid-term 744,745,764. The KDIGO guides suggest informing donors that they have the option of travelling to the recipient's hospital if they wish, while also explaining that the results of renal transportation are excellent 9.

As a general rule, the means of transport to be used is the one which makes it possible to keep the duration of ischemia below 8hours in a cost-effective way 543. Transport, if necessary, may be terrestrial (in an ambulance, hired car or high-speed train) or by air (in a private or commercial flight). The ONT has specific agreements that permit the transportation of a graft in the aircraft cabin, looked after by the crew, at no cost to the healthcare system.

The procedure also stipulates that the nephrectomies from all of the donors in the same cycle without an altruistic donor will take place simultaneously, except in exceptional cases. This condition was established to minimise the risk that one recipient in a cycle would not receive a kidney after their original donor had been nephrectomized.

In any case, the scheme provides for different scenarios of unexpected events:

The kidneys in one cycle have been collected and one engraftation cannot take place: the kidney will be transplanted into a patient in the waiting list of the hospital where the nephrectomy took place and the hospital will return one kidney to the recipient's hospital. The recipient who has not been transplanted will subsequently receive priority in the waiting list.

If the unexpected event (during donor nephrectomy, bench surgery, transport or other circumstances) invalidates one of the kidneys, the other transplantations will take place as planned. This circumstance will be considered an adverse event and the biovigilance system will be notified (the coordinators of the autonomous communities involved will be informed) and the case will be investigated, to discover the origin of the fault and establish preventive measures. In this case the recipient who has not been transplanted will subsequently receive priority in the local waiting list.

In the case of an altruistic donor chain with a bridging donor who does not proceed with the donation after this has already taken place in part of the chain (due to a change of mind or a health problem while waiting, etc.) the recipient who is left without having received a transplant will receive a deceased donor kidney from the hospital of the bridging donor.

• •

  All altruistic donors should be assessed using the same criteria as any other living renal donor, and the exploration of their motivations, expectations and social and family support will all be especially relevant (NG).

• •

  It is recommendable that all altruistic donors should initiate transplantation chains, as this offers the greatest benefit in terms of the number of transplantations. Nevertheless, they should be informed of the possibility of donating directly to the waiting list (B).

The terms “altruistic donor”, “Good Samaritan” or “non-directed donor” are used to refer to those individuals who donate an organ to somebody they do not know who needs a transplant. In this document we refer to them as “Altruistic Donors” 172.

In Spain, after being fully informed altruistic donors may decide to donate in two different ways:

By donating an organ to someone in their local waiting list (anonymously to someone they do not know). In some countries such as the United Kingdom they firstly seek a compatible recipient among those with national priority, and if one cannot be found, by default all altruistic donors then initiate a chain of transplantations 2.

In paired renal donation the final recipient at the end of the chain is also selected from the local waiting list. However, the expected benefit in terms of the number of intermediate transplantations performed is greater. The KDIGO guides recommend informing altruistic donors of the greater benefit in number of transplantations when they start a chain 9.

Altruistic renal donation is increasingly accepted as a strategy to overcome the lack of organs for transplantation 765,766. From 11% to 54% of people in the world are estimated to be prepared to make a living renal donation to patients with ESRD with whom they have no previous tie 767,768.

However, altruistic renal donors are especially relevant when they are included as complements in Domino Renal Paired Donation (DRPD) 649. This is why different countries, such as South Korea 769, the United States 749, Canada 769,770,771, the United Kingdom 772, the Netherlands 773 and Spain have developed altruistic renal donation schemes with excellent results 49.

To centre on European countries, and more specifically on those which have obtained the best results, altruistic donation rates in the past 6 years have accounted for from 8% to 12% of total living donor activity in the United Kingdom and the Netherlands, respectively, while this percentage in Spain accounted for less than 1% 774,775. Nevertheless, it should be underlined that the Spanish scheme has been able to multiply the benefits of altruistic renal donation, obtaining a rate of efficacy for each altruistic donation of 3 transplantations, as well as including long chains through the use of bridging donors. From 2010 to 2018 14 chains started by an altruistic donor have taken place in Spain: 6 with two links, 3 with three, 4 with four and 1 with six links, adding 43 transplantations to the paired renal donation scheme, increasing its efficacy from 27% to 33%.

The protocol for the evaluation of a potential altruistic renal donor was published by the ONT in 2010, conjointly with a multidisciplinary committee of experts in different aspects of living donor KT procedures: nephrologists, immunologists, urologists, transplantation coordinators and experts in bioethics and law 172.

All altruistic donors should be evaluated following the same criteria as any other living renal donor (9), as described in the corresponding section of these recommendations.

Some national guides, such as the one for the United Kingdom, emphasise the need for all altruistic donors to be assessed by a qualified mental health evaluation professional prior to donation (2). Nevertheless, in Spain this is a requisite sine qua non for all renal donors 41.

The peculiarity of the Spanish scheme lies in the fact that the assessment of each altruistic candidate donor is divided into three consecutive phases, all of which have to be passed in order to continue with the process. All three phases are coordinated by the ONT, except for in Catalonia where this function is performed by the Organització Catalana de Trasplantaments (OCATT)172:

An initial semi-structured interview in the ONT/OCATT or in a hospital with experience in paired LDKT. This has two aims, firstly to inform the candidate about the process and, above all, to gather data on their sociodemographic, motivational and health variables, before finally referring the candidate to the authorized hospital(s) in their Autonomous Community, if they pass this initial triage.

The first hospital assessment, in a hospital that is experienced in evaluating living renal donors. This assessment has the purpose of ruling out clinical contraindications for donation.

The second hospital assessment, which will take place in a hospital that is authorized in the Paired LDKT Scheme. This has the aim of ruling out surgical and psychological contraindications, as well as ones in connection with their social and work-related support.

We recommend exploring the underlying motivation, which has to stem from altruistic eagerness (B).

We suggest informing potential young donors that they could consider donating at a later stage of their life (NG).

We suggest waiting for a reasonable time after the first interview, encouraging the candidate to reflect and consider the information that they have received (NG).

The whole process must guarantee (ethically and legally) that the donation is selfless and that the candidate donor seeks no economic benefit, publicity or personal promotion. In case of suspicion, it is especially important to examine the altruistic past of the potential donor, as well as their family support (which should be strong) and their economic situation (which should be sound) 172.

Apart from the information which all living renal donors should receive, in their first contacts with the donation network potential altruistic donors should also be informed of the following points:

That for the process of study and assessment they will have to travel to a hospital with experience in paired renal donation, and that this may be some distance away from where they live. Nevertheless, the convenience for a potential donor will always be taken into consideration when there are several options 172

The regulation governing the confidentiality and anonymity of the procedure, ensuring that the donor accepts this before continuing 9,41

The risks/benefits of transporting the kidney and the safety mechanisms in place to ensure that an collected kidney is transplanted, even though adverse events may occur 9

That they will not be able to select a specific date for donation, although all necessary efforts will be made to respects the time periods which the candidate says are preferable. 2,172

That participation in the scheme requires their specific informed consent9,172,543, for which they must have been previously informed and have understood all of the specific questions described in this section.

Recommend a period of time after the first interview, encouraging them to think about all of the additional information they have received and to reflect on their final decision. This is considered to be good practice, and in Spain donors are able to take the time they need, although in the majority of cases an answer is received in less than one month (2).

In the case of altruistic donors, there are particular considerations in connection with their lack of any ties with the recipient, and this question has to be examined meticulously during the assessment process 743. They have to be prepared for possible situations such as having no information after donation about how the recipient is progressing, or hearing that the transplantation had not succeeded. Although no specific data exist in Spain, in other countries it has been observed that donors need to know that the recipient is doing well 776.

The candidate should be informed about the hypothetical possibility that in the future they may need the kidney that they currently wish to donate, for somebody important and close to them: a child, their partner or a brother, etc. or that they may need it themselves 172.

The study of altruistic donors has removed many pre-existing doubts about their motivations 777. Nevertheless, to prevent any future problems in the mental health of altruistic donors, their underlying motivation has to be studied, verifying that it stems from altruistic eagerness and that it results from their positive aspects rather than any motivation based above all on psychopathological tendencies. It will therefore be useful to explore the altruistic actions of the individual in the past 172. Some questions that may help to explore this facet are shown in Table 16.

As is the case in Spain, in other countries donors have been found to be essentially motivated by a desire to help others, and that they think that they will only experience minimum drawbacks.

Another subject that is discussed in the field of altruistic donation is the age of the donor, particularly in the case of young adults. The majority of concerns here arise in connection with whether the youngest donors are more likely to regret their decision. Although there is no evidence to suggest that this is the case, it may be useful to include questions for younger donors about why they wish to donate now, and whether they could consider doing so at a later stage (2).

Another aspect where altruistic and conventional donors seem to differ consists of their social support and the perception that they need help and attention. Some altruistic donors do not tell their loved ones about their decision, as they do not feel that they are sufficiently understood by those close to them. Nevertheless, a lack of social support could finally lead to the donation not occurring (2). This is why it is important to identify their relationship with their family at an early stage, and it is recommendable to encourage them to let their loved ones know about their decision. This will allow them to gain their help during convalescence after nephrectomy, preventing them from abandoning the process once it has begun due to pressure from those close to them. 754

After approval by the hospital ethics committee, the individual in charge of the scheme in the hospital informs the ONT of the altruistic donors whose assessment has ended, and they are registered in the paired renal donation database 172.

If the donor has decided to donate directly to the waiting list, the hospital which assessed them will select one of its recipients, based on the waiting list recipient selection criteria.

If the donor has decided to initiate a chain of transplantations the procedure will be similar to the one established for paired renal donation, as described above, with the following differences:

The other hospitals taking part will have to be informed at least 15 days beforehand that a new extraordinary round of paired donations will take place, due to the entry of a new altruistic donor into the scheme (if it is to take place outside the established three annual rounds). The purpose of this is so that the other hospitals will be able to add new pairs which have been completely studied, so that they can benefit from this option.

Inform the hospital which brings the altruistic donor that it has to select a recipient from its waiting list for the end of the chain.

There is no limit to the number of links in altruistic donor chains. For chains involving more than four pairs, or in those when the starting times agreed with the altruistic donor are delayed, one of the donors may be proposed as a bridge, so that the chain will go forwards in several phases. This option should be considered from the start in the hospitals involved, so that they are able to agree on it with the affected donors. It is recommendable that the different phases should not be more than one or two weeks apart.

The long-term post-donation risk of hypertension is higher than it is for an equally healthy population which has not undergone nephrectomy (Quality of evidence: B).

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  The risk of mortality due to any cause and of cardiovascular events over the long-term does not differ from that of the healthy control population (B).

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  We recommend informing donors of the risks of renal and cardiovascular disease associated with obesity, actively recommending changes in their lifestyle together with weight control (B).

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  Preventing cardiovascular risk factors during post-donation follow-up will contribute to maintaining the health of the donor over the long-term (NG).

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  Knowing the potential risks over the medium and long-term for a potential donor and informing them accordingly is fundamental in guiding their decision-making and the process of study and selection by the transplantation team. Studies with a long-term follow-up and a large number of cases (given the scarcity of expected events) are necessary to know the long-term risks that can be attributed to renal donation. On the other hand, donors are a rigorously selected group in very good health. The control population will therefore have to be comparable, not only in terms of demographic factors but also medically, to prevent under- or over-estimation of the risks in donors 778.

Most of studies are retrospective, observational and based on single centre or national registries. 95% of them are observational and half of them had short follow-up times (≤1 year), and most of them refer to results in connection with the GFR, arterial pressure and peri-surgical complications 779.

Four studies analysed mortality and cardiovascular events over the long-term with a prolonged follow-up and a representative sample size. They use a selection of individuals with similar health criteria to the donors. Three of these studies found no increase in mortality or cardiovascular events in the donors 120,780,781. Although the remaining study contradicts the other three 37, it has two limitations: (a) the control population is almost 10 years younger on average than the donor population, indicating a distortion in pairing and a clear advantage for the controls (as age is a factor that is associated with mortality), and (b) there was a large percentage of cases without information on variables such as their BMI or smoking, and the analyses were performed with and without data imputation. The results for cardiovascular mortality vary depending on whether cases with or without imputation are used, weakening the final result. A systematic review found no evidence which suggest an increase in the risk of overall mortality, cardiovascular disease or hypertension in living donors compared with non-donor populations 782. Based on current information there is no evidence of any greater risk of mortality and cardiovascular events over the long-term in donors. Nevertheless, further studies are required with a follow-up longer than 20 years to analyse the impact of donation over the very long-term. In any case, the absolute risk of mortality and cardiovascular events is very lower, lower than or similar to that of the general population 33,783,784 and healthy controls 120,780–782.

Both of the analyses which included a large number of donors and controls show a risk of hypertension that is significantly higher in the donors after follow-up periods of 6 785 and 11 years 786. In the first analysis, the appearance of hypertension in the control group was associated with a greater than expected annual fall in filtration, while in the donors it was associated with a halt in the foreseen rising curve for filtration after donation. In a series of 3,700 renal donors who were normotensive before donation, after an average of 16 years follow-up 25% had developed hypertension 787. The associated factors were higher BMI, smoking, dyslipidaemia, familial history and older age. With current evidence, the risk of hypertension over the long-term in donors is higher it is compared with an equally healthy population that has not been nephrectomized. Once again, long-term donor follow-up is fundamental for early detection and treatment of hypertension if it arises.

The prevalence of obesity has increased over recent decades in the general population. This has led to an increase in the percentage of potential donors with a BMI ≥30 Kg/m2 who are assessed in LDKT schemes. Obesity is associated in the general population with an increased risk of diabetes, metabolic syndrome, hypertension, ESRD and mortality 788. Several authors have also observed an increased risk of hypertension, diabetes or ESRD when following up obese renal donors 274,789–791. The clinical guides contraindicate donation when BMI ≥35 Kg/m2, although there is no agreement on moderately obese patients with a BMI ≥ 30 Kg/m2, and the British Guide and the KDIGO Guide suggest that the decision whether to accept a donor or not should be individualized in each hospital, depending on other associated risk factors for the donor in question 2,9.

Few studies have analysed the possible implications of obesity for donor mortality over the long-term. Recently, and although the level of absolute risk was low, an increase in mortality over the long-term has been described in donors with a BMI ≥30 Kg/m2271. This datum underlines the need to insist on the importance of sufficient weight loss in potential donors, and during the subsequent follow-up, with lifestyle change programmes if necessary.

The fall in the GFR observed after nephrectomy is not associated with an increase in mortality or cardiovascular disease (B).

• •

  After elective nephrectomy the GFR in donors falls by 20%-30% in comparison with the pre-donation rate, and up to 15% of donors have a GFR<60ml/min in the post-nephrectomy follow-up 792,793. It is important to underline that the gradual fall in the GFR which characterises CRD and the loss of renal function following donation are not comparable. The donor is a healthy subject whose nephron mass has fallen suddenly due to the effect of the nephrectomy. This leads to the development of compensatory hyperfiltration mechanisms in the remaining kidney, which was previously healthy, that are unconnected with glomerular hypertension, but rather are benign mechanisms such as a possible increase in the filtration surface or glomerular plasma flow 794,795. The majority of donors therefore show a compensatory rising curve of their GFR which remains during several years after donation 207,257.

In patients with CRD, falls in the GFR are associated with an increase in cardiovascular risk 796–798. The presence of albuminuria, on the other hand, amplifies this association. In any case, a patient with CRD cannot be compared with a donor.

In the Framingham cohorts or NHANES I, moderate falls in the GFR were not associated with increased risk of cardiovascular disease 799,800. In the PREVEND group 801, in the absence of proteinuria, an eGFR of 30-59ml/min/1.73m2 was also not associated with an increased risk of cardiovascular disease. However, other studies 243,802–805 found an association between eGFR <60-75ml/min and cardiovascular mortality, especially if it was also associated with the presence of albuminuria. The discrepancy between these results may be explained by differences in the risk factors for renal and cardiovascular disease in the different cohorts. Once again, due to its heterogeneous nature the general population would not be comparable with donors.

To isolate the impact of nephrectomy on cardiovascular risk in donor studies with a prolonged follow-up would be necessary, with a representative sample size and a paired control population that is comparable with the donors not only in terms of demographic factors but also in morbidity and cardiovascular risk factors. That is, equally healthy populations as the donors but without having been nephrectomized. Studies of healthy subjects who have been nephrectomized due to other causes are useful in analysing this problem. Narkun-Burgess et al. 806 compared mortality after 45 years of follow-up in two groups of soldiers after the Second World War. The first group was composed of 62 veterans who had lost a kidney as a war wound, and the second group was composed of soldiers who had not suffered nephrectomy. The authors found no differences between the survival rates in both groups after almost five decades of follow-up. Recent studies found no differences in survival or cardiovascular events between donors and healthy selected controls 120,780–782, and the discrepancy of the Norwegian study 37 may be due to the limitations described above. With the available evidence it cannot be said that the reduction in the filtration rate observed after donation is associated with an increase in mortality or cardiovascular disease.

Finally, when evaluating how a fall in the GFR influences donor cardiovascular risk and mortality, other factors should be mentioned which may determine their long-term evolution. On the one hand, the initial assessment and selection studies play a fundamental role here. It is necessary to know the exact basal GFR of the donor because among other factors, renal function after donation will be determined by this. The formulas used to estimate renal function have a margin of error of ±30% 807. When using formulas to select potential candidates, some may donate when their filtration rates are non-optimum 205,808, so that they would form a subgroup at risk of developing renal and cardiovascular disease in the future. On the other hand, it is possible that there is a group of donors with less renal capacity (due to low weight at birth or prematurity) or a genetic predisposition the additional risk of which was not analysed at the moment of selection 809. These donors may have a higher risk of hypertension and albuminuria during follow-up 810,811, especially if situations of greater demand are added, such as weight gain or metabolic syndrome after donation. Finally a very long follow-up and the correction of additional cardiovascular risk factors may influence their evolution 47. In fact, although the cases of ESRD diagnosed in donors during the first decade have been said to be due to immunological or genetic factors, in subsequent decades factors such as hypertension and diabetes are the predominant causes 812.

We suggest informing female donors of fertile age of the increased risk of gestational hypertension and preeclampsia in pregnancies after donation, and that here is no evidence of other adverse results for mother or foetus (C).

It is important to inform potential female donors of fertile age about the risks associated with a future pregnancy. Eight relevant studies have been published to date which include almost one thousand pregnancies after renal donation in 800 donors (the majority of whom were Caucasian).

Three single centre studies 813–815 in the 1980s and 1990s included a small number of cases, without controls and based on surveys. None of these studies found a higher risk of deterioration of the GFR, proteinuria or maintained hypertension associated with donor pregnancy. In 2009, a Norwegian study compared the complications of pregnant women after donation with two unpaired control groups: pregnant women prior to donation and pregnant women selected at random from a registry of births in the general population 816. The percentage of preeclampsia in the post-donation pregnant women was significantly higher than it was in the donors prior to nephrectomy and the registry control group (5.7% vs 2.6% vs 3.1%; p=0.026). The small number of events made multivariate analysis impossible. A North American study found similar results, although without a non-donor control group 124. A Canadian study of female renal donors who had been pregnant compared their evolution with healthy non-donor women who were similar in age and access to social and health services 123. There were higher rates of both preeclampsia and gestational hypertension in the donors than they were in the control group (11% (15/131) vs. 5% (38/788), OR 2.4 p<0.01). There were no differences in the incidence of Caesarean births, prematurity or low birth weight and perinatal or maternal mortality. Once again the low number of events restricted multivariate analysis. Finally, two more recent studies, one in an Asian population 817 and the other based on a North American registry 818 compare post-donation pregnancies with control group of the general population, and they found no significant differences in terms of adverse maternal-foetal results.

Further studies are needed to establish definitive recommendations. The studies published to date show a small number of events, and they lack a control group that was paired according to donor characteristics. Although we are able to inform potential female donors of fertile age about the risk of preeclampsia and gestational hypertension, the absolute risk of this is low and it is not associated with an increase in preterm births.

According to American registry data more than 150,000 individuals had made a renal donation while alive. Their incidence of ESRD was 10-30 events per 10,000 donors in 15 years 35,229, and their risk varied depending on their age, sex, race and time post-donation 224.

Many transplantation schemes have established policies which give priority in the waiting list to previous renal donors with ESRD who do not wish or cannot select an anticipated LDKT. In the U.S.A. from 1996 and in the Netherlands from 2011 they have been assigned priority to minimise their time in dialysis 127,819. Other countries which give priority to these cases are Sweden, Norway, Belgium, Luxembourg, Austria, Croatia and Slovenia. In Spain each transplanting hospital is responsible for following up its living donors; if necessary they are able to establish policies which give priority to certain cases.

Given the scarcity of ESRD cases in each LDKT scheme, there is very little bibliography on how these patients progress before and after transplantation. Multicentre registries are essential to gain an understanding of the problem as a whole. All efforts are directed towards ensuring that affected donors progress well, but if they develop ESRD it is the responsibility of the transplantation hospital to return them the therapeutic benefit which they had created for the scheme in the past.

Early mortality deriving from renal donation is very low, and it is lower than the level corresponding to similar elective procedures (B)

• •

  The long-term mortality rate due to neoplasia in donors is no different from the rate in a comparable control population (B).

• •

  According to American registry data mortality in the first three months after nephrectomy stands at 0.03% 118,120,820. This is lower than the rate corresponding to other surgical procedures, such as laparoscopic cholecystectomy or nephrectomy for other reasons, although it is higher than the estimated risk of peri-partum mortality 820. The most frequent causes of death are haemorrhage, cardiovascular events and pulmonary thromboembolism. After this time, mortality in the first year is comparable to that of healthy controls 120. Apart from the studies described above on survival and cardiovascular risk, two recent publications found no differences in terms of mortality between donors and healthy controls after average follow-ups of 8 years821 and 11 years822. Neoplasias were the most common cause of death in the follow-up of each of the groups in both of these recent studies. Several registry studies confirm this finding 784,823,824. However, the lack of a control population makes it impossible to draw conclusions regarding risks. None of these publications permits the conclusion that donors are at higher risk of mortality due to neoplasia than is the case for the general population. Nevertheless, the importance of extensively ruling out neoplasia before donation has to be underlined, and this should include recent urological and gynaecological examinations, while also ruling out malignity in suspicious skin lesions before continuing with the process.

• •

  We recommend KT due to its lower mortality rate in comparison with overall patient survival in the waiting list, regardless of the type of transplantation. These differences are detectable after the third month post -RT (Quality of evidence: B).

• •

  We recommend shortening the time spent in dialysis prior to transplantation, as this is a factor that can be modified, and it strongly influences long-term survival after transplantation (B).

• •

  We suggest that LDKT should always be considered as the first option for patients with CRD, and above all in unfavourable clinical situations (young patients, ones with a high comorbidity, a high level of surgical complexity or highly sensitized patients) who have fewer possibilities of accessing a deceased donor renal transplant (C).

Patients with ESRD have significantly higher mortality than the general population and those with a functioning renal graft 826. To centre on patients who are KT candidates, longitudinal studies have shown that the overall mortality of patients in the waiting list is significantly higher than mortality in transplanted patients, independently of the type of transplantation. These differences may be detected after the third month post -KT 827. The most frequent causes of mortality during the first year of replacement therapy are cardiovascular disease, followed by infectious complications 828. There is not only a clear benefit in comparison with dialysis in terms of recipient morbimortality, as this benefit also includes the economic repercussions for healthcare systems 829.

Rarely do we have to choose between a LDKT that is “suboptimum” or “ideal” for a potential recipient. The alternative to a LDKT from a donor of any age is to remain in dialysis, waiting for a suitable organ from a deceased donor. The annual mortality rate for patients in dialysis in Spain stands at 15%-16%, and it is far higher in elderly patients, a significant percentage of whom die while they remain in the waiting list 830. To complicate this situation even more, comorbidity may increase over time in patients who are receiving dialysis 831, and the higher their degree of comorbidity, the more likely it is that they will be excluded from the KT list 832.

Moreover, a long time spent in the waiting list may increase the possibilities of receiving blood transfusions due to the appearance of additional complications. This may give rise to a higher risk of sensitization against a possible graft due to the formation of anti-HLA antibodies, thereby prolonging the waiting time even more and permitting the emergence of comorbidities 833,834.

The duration of dialysis prior to transplantation is still an important and potentially modifiable factor in long-term survival after transplantation. Unfortunately, young recipients may take some time before accessing a KT due to the scarcity of younger donors. 56% of the patients included in the waiting list in the United Kingdom in 2011-12 received a transplant after 3 years, 6% had been eliminated from the waiting list and 5% had died while awaiting a donor 825. This situation often arises, with long waits before transplantation. Mortality while waiting is another important matter when considering a potential living donor among transplantation options.

We recommend LDKT even when donors are over the age of 69 years, as it is a beneficial alternative to remaining in dialysis or to spending more time in the deceased donor waiting list (B).

• •

  Graft survival is shorter in recipients with living donors older than 70 years than it is in recipients with standard donors, although patient survival is similar (B).

• •

  We suggest that donor renal function may be more important than age in the results of LDKT, although this is not confirmed by all studies (C).

• •

  We suggest that donors should not be excluded solely on the grounds of age. Older donors should be accepted or rejected after an exhaustive medical assessment (NG).

• •

  The persistent disparity between the number of patients waiting for a RT and the available organs in the group of deceased donors, together with increasing knowledge and familiarity with the results of LDKT for donors and recipients, has led the transplantation community to consider candidate donors who would have been ruled out in the past due to their demographic characteristics or intrinsic medical problems.

The areas of uncertainty associated with the short- and long-term results for medically complex living donors should be considered depending on the cause of this clinical situation (age, hypertension, obesity, DM, lithiasis or oncological problems) as described in other chapters in these recommendations.

In terms of results for the recipient, several alternative options should be considered: the probability of receiving a transplantation from a deceased donor using standard or expanded criteria, the result of the said transplantation, the morbidity and potential risk of mortality while waiting for a suitable organ from a deceased donor, the suitability/risks associated with emergency rather than elective surgery, the result that can be expected with such an organ from a living donor in comparison with the foreseeable life expectancy of the same, etc.

The literature is sufficiently conclusive in supporting LDKT from older donors for at least one cohort of patients. Renal function gradually falls with age, and the renal function of an older living donor may be reduced 835. Several single centre or registry studies show poorer results in terms of renal survival after LDKT as donor age increases 560,836,837. In comparison with the recipients of grafts from standard donors, graft survival falls in recipients whose living donors were ≥70 years old, although patient survival was similar. Renal transplantation recipients from older donors had better graft and patient survival than did recipients with expanded criteria donors 560 (Table 17). In general, it seems to be beneficial to use older LDKT donors, equivalent to waiting for a deceased renal donor 560. Estimation of the GFR has been shown to be an important factor in transplanted renal function 216, and it has been suggested that donor renal function may be more decisive than their age for the final results, although this has not been confirmed by all studies 838.

Older donors are more likely than younger ones to be excluded from donation due to problems discovered during their medical assessment. Nevertheless, each case should be considered individually, and if an older donor is considered suitable after a rigorous medical assessment, and if their renal function is normal after correction for age and sex, there is no evidence that they should be excluded from donation solely due to their age 839,840. In a similar way to age, the advisability of assuming that a live donor kidney will have “non-ideal” survival in the recipient (due to comorbidities, renal function or HLA compatibility …) must also be considered on an individual basis for each particular recipient.

We suggest that “high risk” recipients should not be automatically excluded, to prevent unfairness in access to KT. Although the results in terms of survival may be statistically “worse” due to their associated comorbidities, each case should be assessed individually after the relevant studies (NG).

• •

  We suggest that, with some exceptions, patients accepted for deceased donor KT are also suitable for a LDKT (C).

• •

  We suggest that the LDKT option should not be considered when it is estimated that post-transplantation survival will be not reach two years, or when there is a high probability of renal disease relapse in the graft (C).

• •

  LDKT may offer opportunities to patients whose perioperative risks for an emergency procedure are considered to be unacceptably high, although they may be acceptable for an elective KT, optimizing harvesting from an optimum donor, with a team to manage any special difficulties, commencing immunosuppression before transplantation and minimising any delay in graft functioning (NG).

• •

  We suggest that the acceptance or rejection of LDKT in high-risk patients should be based on the opinions of expert multidisciplinary teams. A lack of data makes it impossible to make clear recommendations for highly complex recipients (NG).

• •

  The success of a KT scheme cannot be judged solely on the basis of recipient and graft survival in patients with ESRD. There may be errors in data interpretation, and it is more probable that a scheme which takes no risks will give results corresponding to excellent recipient survival. This policy may potentially be associated with unfair lack of access to transplantation for patients who are highly complicated in surgical terms, or at immunological risk and subject to a higher risk of death in the waiting list. It is not easy to measure the difficulty certain populations have in accessing transplantation 841.

To ensure terminological uniformity, a high risk recipient is one with a significantly higher risk of death, complication or graft failure due to pre-existing comorbidity or their immunological status. Statistically, this is equivalent to poorer results for the graft and patient survival. There are no robust scoring systems for this risk evaluation. Although it is probable that models will soon be developed 842, it is known that with the uncertainty of current predictive tools there is still dependence on the clinical judgement of the transplantation professionals who are involved. The recent British guidelines, and solely as a recommendation with a low level of evidence (C2), state that in cases where the probability of post-transplantation survival is less than two years, the option of LDKT should not be considered LDKT (2).

LDKT may offer opportunities to individuals whose perioperative risks for an emergency procedure are considered to be unacceptably high, as they may be suitable for elective transplantation. The advantages include: recipient optimization, resolving and controlling their active health problems beforehand, the ad integrum availability of all of the personnel in the multidisciplinary team (surgeons, anaesthetists, intensive care specialists, nephrologists, immunologists and nursing staff, etc.), with the administration of immunosuppressant drugs prior to transplantation and a high quality organ with very low risk of retarded graft functioning.

The key question is whether, although these patients can expect a relatively worse transplantation outcome in comparison with standard risk patients, their result may be better than it would be if they remain in dialysis. The persistence of cardiovascular disease, pulmonary disease, obesity, diabetes o hypertension will affect the survival of renal patients whether they receive a transplantation or are dependent on dialysis 843.

Another group of patients who may be considered complex is composed of those at high immunological risk and sensitized. LDKT recipients with HLA incompatibility are often excluded from survival analysis in the results of LDKT as their rates of survival are not as good as those for compatible transplantations without antibodies. However, for some patients transplantation in these circumstances is the only way they will achieve independence from dialysis. The recommendation is to establish a specific scheme to select a donor against whom the recipient does not produce antibodies. This objective can be achieved in LDKT by paired exchange strategies. Patients with DSA should only receive a transplantation if these measures cannot be applied and after desensitization programmes. The presence of DSA that can be detected using techniques other than complement-dependent cytotoxicity is considered to be a risk factor in itself but not a contraindication 101. In the case of HLA incompatibility, the use of desensitization techniques in ABOi KT offers similar long-term results to ABOc KT 53.

The donor and the recipients should be informed of the possible risks and results. Although this is also the case for living donation transplantation in general, it is particularly important for highly complex recipients, where the risk of an adverse result is higher than it is in cases of standard transplantation. It is proves impossible to reach an agreement within a particular transplantation hospital due to differences of opinion on the degree of risk, the option of referral to another hospital for a second opinion should be discussed with the potential recipient and donor.

Although we unify the inclusion criteria of our protocols, clinical practice will surely eventually lead us to differences in who we include. Nevertheless, this would not be a problem and it would be corrected by the patient's freedom to request second or third opinions about the advisability of a LDKT. It is important that the decision to transplant into high-risk recipients should not be influenced by the sometimes unwarranted concern about the possible results. It is very difficult to set standards for results in this LDKT group, given the heterogeneous nature of the patients and the differences between the definitions of what constitutes high risk between different units.

Healthcare coverage by the National Health System or private insurers must be guaranteed for the direct costs of pre-transplantation assessment and the medical and surgical interventions in the LDKT process. It must be ensured that the donation will be economically neutral for the donor, facilitating reimbursement of the direct and indirect costs of the same. (Quality of evidence: B)

For foreign living donors, the relationship between the donor and recipient must be verified, and the former must comply with the legal requisites to enter and remain in the country during the LDKT process. (B)

The logistics of the process should be organised in such a way that evaluation of the viability and compatibility of the donor and recipient takes place in the most effective and fluid way possible, always offering complete information, particularly to the donor, about the risks they are accepting and the expected benefits of the LDKT.

As well as collaborating with the nephrologists of the LDKT scheme by informing patients, professionals in the dialysis units and ESRD units of the hospital and others for which the transplanting hospital is the referral hospital, the individual in charge of coordinating the LDKT process may also collaborate in the following 10 phases:

The process commences with the interview by the responsible nephrologist and the potential donor. This permits an initial evaluation of the feasibility of the process and factors in connection with the protection of the donor. According to Royal Decree 1723/2012, of 28 December41, it is necessary to verify that the principles of voluntary donation, altruism, confidentiality, the absence of a desire for profit and freedom from charge have been fulfilled. The laboratory tests should then be requested, HLA and the imaging tests described in other sections of this document. Visits to the other professionals involved in the scheme also have to be arranged, to gather all of the opinions that make it possible to discuss the case in a multidisciplinary way before it is approved or rejected: urology, anaesthesia, psychology or psychiatry and other specialities (vascular surgery, cardiology, oncology and haematology, etc.).

It is advisable to offer a potential donor an interview without the presence of the recipient, to give them a space where they can express themselves freely, revealing their worries and doubts. In this interview the donation process has to be explained once again, clarifying and resolving any questions in a way that will allow them to give their valid informed consent. The importance of the EC should also be explained, together with the legal obligation to appearance in Court, to ratify that the organ is donated freely, without economic or any other form of coercion, and that they have been duly informed.

As this interview with the donor is in private, it is important to verify that the donor fulfils the recommended requisites in the Council of Europe Guide to safety and quality assurance for organs, tissues and cells27 and the ones in these Recommendations, including the evaluation of risk factors and behaviours to minimise the possibility of transmitting infectious diseases–and diseases of other types - to the recipient. Although this task should be carried out by the doctor in charge of assessing the state of health of the donor, it is important that an independent professional should also do so. The latter should, in a coordinated way with the transplantation team, indicate precautionary measures to the donor, informing them of the risks which certain forms of behaviour involve for the recipient.

Documentation has to be requested which accredits the identity of the potential donor and recipients, and which guarantees the relationship between them, although it is the responsibility of the Examining Magistrate to verify the veracity of this documentation.

This fact is particularly important in the cases of live donors who are not genetically or emotionally related, as well as when the donor (and/or the recipient) are foreigners, either individuals from another country who have travelled specifically for the transplantation, or foreign residents in Spain. In such cases, some groups propose that, prior to commencing the tests in the studies of the health of the donor and recipient, an interview should be held to exhaustively review the documentation which proves the tie between them and ensure that both the donor and the recipient are authorised to legally stay in Spain. It is also suggested that the EC should be consulted first to evaluate the advisability of interviewing the donor before continuing with the assessment process.

Foreign donors (and/or recipients) who live outside Spain are recommended to count on a known and trusted medical team in a referral hospital, so that they are able to perform the basic tests in their country of origin which are necessary to assess the suitability of the donor, thereby avoiding unnecessary travel and expense for the donor if the donation is contraindicated. The tests involved may include at least blood group, viral serology and renal function and ultrasound scan. In this case only donors genetically or emotionally related to the recipient should be accepted, for direct transplantation as well as for participation in the Paired KT Scheme of the ONT 543. A legal stipulation is that living donors must be supplied with medical treatment for their recovery, as well as life-long follow-up. It is therefore indispensable to ensure medical coverage in their country of origin, to guarantee medical care for the donor after the donation process. They must also be followed-up encouraging healthy lifestyle habits to help them preserve their health. The above recommendations are contained in a Government Resolution on the principles for the selection, assessment, donation and follow-up of non-resident living organ donors85.

Table 18 describes the documentation used to prove the relationship between the donor and recipient, and we suggest reviewing this based on the origin of the donor and/or recipient.

Appropriately coordinating all of the studies, depending on the needs of the patient, makes it possible to perform them in a short period of time. It also permits monitoring the studies of a living donor, verifying that nothing relevant is lacking and speeding them up. As the Living Donor Route Map and Situation Analysis Document (Documento de análisis de situación y hoja de ruta del Donante Vivo)847 states, the lack of an individual in charge of this aspect (except in hospitals where a clinical route or similar pathway has been implemented) slows down procedures because they have to be done over and above the normal daily work for the professionals involved.

To ensure that donors are completely protected, the interview seeks to discover the nature of their decision-making process and their family and social context, as well as their economic and professional situation:

The decision to donate:

• •

  How they obtained the information on how to become a donor

• •

  Motivations to be a donor

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  Feelings they have experienced

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  Whether they have asked people they know about their decision

• •

  Pressures that may have influenced their decision

• •

  Implications and consequences at every level

Family situation:

• •

  The individuals in their close family

• •

  Family conflicts

• •

  Individuals who would care for them after post-donation discharge from hospital

• •

  How they have planned for the well-being of those who are dependent on them in case of any complication arising, particularly if there are children or family members who live abroad who are economically dependent on the donor

• •

  Professional and economic situation

Profession and employment:

• •

  type of contract, the effects of their decision on their work, the possibility of time off work.

Economic repercussions:

• •

  Measures they have adopted

• •

  Their social situation and family and social support.

The multidisciplinary team will therefore be able to check with the donor and guide them regarding possible reimbursement for the direct and indirect costs deriving from their donation, such as travelling expenses, allowances, lodgings, childcare and time off work, to prevent the donation having a negative economic impact. These aspects are especially important when the donor lives abroad. The National Health System in Spain or the recipient's private insurance policy covers the costs deriving from pre-transplantation assessment and medical and surgical procedures. In the case of private donations, care must be taken to ensure that these costs are paid for by the recipient. Foreign living donors in particular, and most especially if they require treatment that was unconnected to the donation process (such as if a previously unknown neoplasia is detected), then it important to inform the donor that such costs are not covered by the healthcare coverage of the recipient (2,85,848). It is advisable to check that the donor has someone who will be able to care for them, at least during the first days after discharge from hospital (2).

The nature of a valid consent process (free, informed and express) was described in the living donation Ethics Chapter in this document. The LDKT coordinator has to verify that the donor understands the information given and that all of their questions have been answered. Acting as the guarantor of the donor's rights, the coordinator has to verify that their consent is granted expressly, freely, consciously and selflessly. They have to clarify that this decision is reversible, so that at any time the potential donor may withdraw from the process without giving any explanation and without any repercussion whatsoever. In all cases, and in particular for unrelated and altruistic donors, there must be verification that they are under no external pressure and that there no other circumstance which suggests that there is an economic, social, psychological or any other type of conditioning factor.

Depending on the level of LDKT activity, it is recommendable to schedule a regular meeting to discuss all of the cases once they have been assessed as possible living donors and before they are presented to the EC for evaluation. This meeting should be multidisciplinary, with all of the professionals who are assessing the suitability of the living donor candidates in terms of the physical and mental health. This assessment will include nephrology, urology, anaesthesiology, nursing, radiology, immunology, haematology, social work, psychology and psychiatry. The LDKT coordinator will be able to take part in this meeting by offering their opinion as the donor advocate, offering information on the relationship between the donor and recipient, and explaining their social, familial and professional situation. An overall clinical evaluation of the donor and recipient will determine whether they fulfil the criteria set by each transplantation group, and the decision is taken if to approve the case as a living donor for a specific recipient, or if they will enter the National Paired Renal Transplantation Scheme. It is advisable to prepare the Minutes of this meeting to be appended to the clinical history of the donor.

LDKT is facilitated by a specific professional who coordinates the ethical-legal process. In turn they have to guarantee that the hospital where the process of donation, harvesting and transplantation will take place has been expressly authorised for the harvesting of living donor organs by the corresponding Autonomous Community health authority.

We recommend that the EC should meet regularly, especially in hospitals with a high level of transplantation activity. The EC should receive the medical reports on the donor and recipient, as prepared by the nephrologist in charge of the process, as well as the mental state report prepared by the psychologist or psychiatrist and the social, familial and professional evaluation of the donor, which may be supplied by the LDKT coordinator. The nephrologist, the coordinator and other professionals who are considered relevant will attend the EC meeting. After deliberation, the EC will prepare the report which authorises the donation.

The LDKT process coordinator will be able to manage the appearance in Court, agreeing the day and time for this with the Judge, together with the presentation of the documentation and the ratification of the consent. The donor, the doctor in charge of the process and the surgeon in charge of the harvesting and transplantation must all go to the Court. All of them will have to show their identification national card or passport (if the donor is foreign). In the case of a living donor who does not speak any of the official languages of Spain, they must be accompanied in the Court by an independent interpreter who has no ties with the donor, the process coordinator or the transplantation team, after approval by the Judge.

The following relevant documents must be given to the court:

• •

  The application to appear before the Court, signed by the donor.

• •

  Certification of the donor's state of health, signed by a doctor who is independent of the living donor study process.

• •

  Copy of the consent document or the authorization for living donor renal donation

• •

  The EC Report

In the case of a donor in the National Paired KT Scheme, the Judge will be given a copy of the codes generated by the scheme. The Judge will also be given a copy of the Paired KT Authorization Document - generated by the ONT, and which contains the information on the pairs taking part - signed by the donor.

In the Court, the Judge will verify the donor's free decision, and before the Judge those attending will sign the Certificate of Consent for the Donation of human organs between living individuals. The Court will give a copy for the donor's history and another copy for the donor him/herself.

In the case of a foreign live donor, prior to donation the Autonomous Community Transplantation Coordination authority and the ONT must be informed, sending information which verifies the tie, passports and medical coverage of the donor and recipient. In the case of a living donor for paired KT, the KT unit has to inform the ONT that the donor and recipient have accepted to participate in the program. The Codes of the National Paired KT Scheme are obtained from the ONT web portal 543, together with a table showing the hospitals and donors involved in each paired donation and the ONT Paired Donation Scheme Authorization Document, which the donor has to sign. In turn, on the day after the donation, the Autonomous Community Transplantation Coordination authority will be informed and it will be registered in the National and Autonomous systems of the Living Donor Registry and, in the case of a foreign donor, it will be possible to also inform the respective Registry in the donor's country of origin.

The transport and/or reception of the kidney to and from the hospitals involved has to be organised by the National Paired KT Scheme 543. The packaging, preservation and transportation have to be verified according to ONT specifications 849,850 and Royal Decree 1723/2012, of 28 December 41. An internal document of the hospital of origin will be appended, making it possible to identify the donor (ONT Paired Code, hospital clinical history, etc.), the side of the kidney, the macroscopic appearance of the organ, the type of harvesting procedure used, warm ischemia times and the time of renal perfusion and the solution in which the organ is preserved. The report on donor and organ characteristics also has to be included (including blood group and recent serologies, from at least 7 days before donation), in a similar way to the procedure with a kidney from a deceased donor, and according to legal stipulations.

Good communication and coordination is necessary between the different teams taking part in the National Paired KT Scheme, together with the ONT and the Coordinating authorities of the Autonomous Communities involved. This will guarantee that the terrestrial and air transport systems used function at the highest level of efficacy, and that everyone involved is constantly informed in real time about the situation in each hospital. This will make it possible to reduce cold ischemia time to a minimum. Some recent publications in the U.S.A. and Australia, where distances are very long, have described that a cold ischemia time of 16hours or less has no significant affect on renal function 745,851,852. Once the chain of paired transplantations has ended, it is advisable to report any incident that may have occurred during the process so that the relevant corrective measures can be applied, acting to improve the National Scheme. All of the information corresponding to the donation and engraftation should be shown in the clinical history of the donor, either on paper or in a computerized clinical history.

O summarise, LDKT schemes have to scrupulously comply with the legal regulations that are in force. The complete protection of the living donor has to be a priority in all schemes. The work of coordinating the LDKT described here should be carried out by one or several professionals in each authorised hospital, and in Spain this work is done by the TC, wholly or partially. The final aim is to facilitate and coordinate the different stages of the process, ensuring its ethical and legal correctness while guaranteeing the protection of the donor and the transparency of the process, promoting measures that will improve the whole system.