Renal transplantation (RT) is the best therapeutic option of renal replacement therapy.1,2 The rate of kidney donation in 2017 in Spain was 46.9 donation per million of habitants (pmp). RT represents the first modality of renal replacement therapy and it covers a 53% of patients. This has been achieved to a large extent because the acceptance of new donor profiles. In 2011 the death brain donation (DBD) had stabilized and the 2229 RT performed was not enough for the 4524 patients remaining in the waiting list.3 At that time, it was promoted the use of organs from donors with expanded criteria and from non-controlled asystolia donation (ncDCD) aiming to improve the number of RT. The ncDCD model was launched in our country in 1992; it has a complex organization and infrastructure and, therefore, it was limited to a few hospitals.3 At the same time, several European countries had donation programs after controlled circulatory arrest (cDCD), with satisfactory results .4,5

In 2011, the Spanish National Transplant Organization (ONT) in collaboration with hospitals and scientific societies, promoted an institutional plan to stimulate the Maastricht type 3 donation, in which the donor presents a controlled circulatory death in the hospital environment (cDCD).6

In 2012, these programs were launched in several hospitals and the experiences of the first series of cases were published soon after.7 The same year, the transplant working group of the Spanish Society of Nephrology (SENTRA) promoted a cooperative study among the hospitals that had incorporated this donation model (GEODAS-3 study). This manuscript describes and analyzes the data of this national experience.8

The present work is the first analysis of a large sample of RT from cDCD donation collected from many centers throughout the Spanish territory that allows to evaluate the clinical results. Therefore, it serves as a reference for comparison with other procedures and for the promotion of this donation model. The good initial preliminary results reported by some centers are confirmed with this present analysis.7,8

The cases of RT using cDCD have increase from only less than 2% of all donors in 2012 to 26% in 2017.10 With this strategy, the figures of 46.9 donors pmp and 12 cDCD pmp places us, Spain, at the top of the international ranking.10

The incidence of PNF and DGF described in this report is within the range reported by other publications from countries with more experience in the field. The most relevant reference models for this type of RT are Europeans, particularly from the United Kingdom11 and the Netherlands5 and the furthest model from the United States of America.12 A recent meta-analysis compares the results of 3014 RT performed with organs derived from cDCD with those of more than 80,000 DBD and establishes a risk of DGF more than double (OR 2.74 [2.04–3.68].13 Comparisons of results obtained in different countries requires a review of the different protocols, management models, donation and immunosuppression protocol and the profiles of donors and recipients .14 In our country, the use of this type of cDCD donors has been generalized, so that by the end of 2016, 72 centers had cDCD program. However, the reference models in other countries tend to concentrate the experience in selected centers. United States of America publications refer to a type of donor that is 7 years younger than our donors and a percentage of non-acceptance of the organ of 50% for donors over 65 years. The 13-year experience recently published in the United Kingdom presents an average age for the donor similar to ours11 but in our case the range is wider and includes older donors, up to 83 years, with Cr values above 2mg/dl.

Initially the limit for the cDCD donation was: age <65 years, with normal renal function and low comorbidity.6 However, we have seen a progressive widening of the selection criteria once it was learned that one out of every four donors was over 65 years of age and almost half meet the classic requirements that define a donor with expanded criteria. The results of PNF and DGF did not change with the years, so we assume that we had improve from our experience and that is compensated by the liberalization of the selection criteria and the acceptance of the suboptimal donor.10

Nevertheless, analysis of regional registries show that the mortality risk being maintained in waiting list is greater than receiving an organ from a donor with expanded criteria, for example, over 65 or even 75 years.16,17

The pathophysiological process of ischemia-reperfusion injury is different in cDCD and DBD18 which explains a higher incidence of DGF. The agony process prior to cardiac arrest entails a time of warm ischemia that cannot be avoided, and contributes to the organ damage in DBD.18 In the case of uncontrolled DCD, the first period of warm ischemia is much more prolonged, which explains that the DGF is almost the norm.10 In our study, DGF occurs in one out of 2 cases, despite the systematic use of induction therapy and delayed introduction of tacrolimus as a strategy for renal protection in some centers. We have identified the CIT as the most relevant modifiable risk factor and it is established a limit of hours that predicts a significant increase in risk. The annual reports of the ONT shows that there is an increase in the use of machine perfusion of donor with ECMO reaching 30% in 2016.10 The nonuniform definition of DGF event limits the comparison between studies. In our case, DGF is defined as a need for hemodialysis in the first week post-TR, which could justify the higher incidence observed in our series, since cases of DGF can be included with a single session of hemodialysis due to difficult management of water overload. Therefore, it is possible that the lower incidence of DGF in patients that had not received dialysis prior to RT (anticipated RT) or coming from peritoneal dialysis is partly due to a greater residual renal function and less immediate access to the urgent hemodialysis session. This finding is common in other studies.19,20

Although PNF cases are mainly due to problems with organ conservation or surgical procedure, our study shows that CIT is the most important modifiable risk factor. Strategies to reduce early events such as PNF and DGF should focus on improving organ conservation systems and reducing CIT. This is the reason why some authors recommend minimizing this time by sending one kidney to another nearby hospital to achieve in both transplants a CIT less than 12h.21

In a local study already published5 we did not find that DGF had an impact on the posterior survival of the organ. A recent study of great statistical power compares pairs of recipients from the same donor in which one recipient develops DGF and the other had immediate function. This analysis on almost 30,000 RT eliminates the confounding factors of the donor. The risk of graft failure during the first year increases in those with DGF HR 3.75 [3.31–4.24] and even more in those with some acute rejection added to DGF (HR 8.16 [4.72–14.10]). This effect loses strength during the following years, with a risk of 1.16 (1.02–1.31) and 1.19 (0.59–2.23). In addition, DGF carries difficulties with both diagnosis and management; there are uncertainty with the diagnostic, requiring early biopsies and adjustments of immunosuppression, prolonged admission and the cost per process increases.19

Renal function at the first year was close to 60ml/min, so we could be expected good medium and long term survival. Our study does not allow a comparison with the results of the DBD donation, but a recent analysis of the Andalusian regional registry shows that renal function achieved after one year is better in transplants from DBD donors than from DCD (Crs 1.79±0.90 vs. 1.46±0.50mg/dl; p<0.001).22

Although we have collected cases with a follow-up of up to 5 years, our average follow up only allows us to analyze survival at the second year. Survival of the patient and organ censored by death with a functioning graft are similar to the records for DBD.10 The analysis of the risk factors for survival is outside the scope of this first study; such analysis we will performed once solid conclusions can be obtained based on a longer follow-up.

The main limitations of the present study are a mean follow-up of only 2 years and also the absence of a common protocol for the extraction and preservation of the organ, as well as for the immunosuppression treatment regimen. However, we have included more than one third of all RT with organs from cDCD10 and the sample size is sufficient to adequately represent the general situation in Spain. The direct involvement of clinicians in the design of the database and in the collection of information is a guarantee of the quality of the information.

Some authors warned about the risk that the cDCD donation would anticipate to the DBD, so an increment in organ donation may not be achieved.11,20 Although this analysis is outside the framework of the GEODAS-3 study, we can use the reference of the ONT records to confirm that the cDCD model has supposed a net increase of donors without reduction of the DBD donation rates,10 something that confirms the model of the United Kingdom after 13 years.11 The present work adequately represents the reality of RT with the cDCD donation model and contributes to its promotion and implantation in the rest of the transplant centers in our country.

The cDCD programs has been extended because they present an organizational complexity that is quite accessible and allows an increase in rate of donation without compromising the DBD. The learning curve seems to be accomplished, and our results are similar to those reported by countries with a long tradition. The CIT is the most relevant modifiable risk factor. Pending an analysis of organ and patient survival in the longer term, we have our own and current results that support the development of this joint strategy.

This project is sponsored by the SENRA Group of the SEN, the RedinRen 16/009/009 RETYC ISCIII, the Renal Iñigo Álvarez de Toledo Foundation and a collaborative grant from Novartis, Astellas and Sanofi through the Puerta de Hierro Health Research Institute-Segovia Arana.

The authors declare that they have no conflict of interest.