Clinical approach to kidney disease in kidney recipients in Spain

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Campistol, Alex Gutiérrez-Dalmau, Josep Crespo, Núria Saval, Josep Maria Grinyó" "autores" => array:6 [ 0 => array:3 [ "nombre" => "Josep M." "apellidos" => "Campistol" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Alex" "apellidos" => "Gutiérrez-Dalmau" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Josep" "apellidos" => "Crespo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Núria" "apellidos" => "Saval" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:4 [ "nombre" => "Josep Maria" "apellidos" => "Grinyó" "email" => array:1 [ 0 => "jgrinyo@bellvitgehospital.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 5 => array:1 [ "colaborador" => "Grupo de Estudio Observa" ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Unidad de Nefrología y Trasplante Renal, Hospital Clínic, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Miguel Servet, Zaragoza, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario Dr. Peset, Valencia, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Novartis Farmacéutica S.A., Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Unidad de Nefrología y Trasplante Renal, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Actitud clínica frente a la disfunción renal en receptores de un trasplante renal en España" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1285 "Ancho" => 2694 "Tamanyo" => 226068 ] ] "descripcion" => array:1 [ "en" => "Changes in immunosuppressive treatment." ] ] ] "textoCompleto" => "IntroductionThere has been a recent progress in immunosuppressive treatment, however long term survival for kidney transplant patients has not increased significantly over the last ten years.Chronic kidney disease (CKD) in kidney transplant patients (KT) is a frequent complication, the treatment of which is not usually simple, since it depends, largely, on the clinical symptoms of each patient and the severity of the dysfunction. CKD is related to various factors; such as the characteristics of the transplant (donor, conservation), the specific features of the recipient, the immunosuppression treatment and the clinical outcome of the transplant.<a class="elsevierStyleCrossRef" href="#bib0170">1</a>The most frequent causes of loss or kidney transplant failure are CKD or death of the patient with functional kidney transplant. This is, observed at a rate of 3–5% per year.<a class="elsevierStyleCrossRef" href="#bib0175">2</a>CKD in kidney transplant is defined by a gradual deterioration of kidney function, with interstitial fibrosis and tubular atrophy that causes proteinuria, high blood pressure, and a gradual increase of serum creatinine. Mild CKD (grade I of Banff) is observed in nearly all transplants at the end of the first year of transplantation, and grade II and III, is present in 90% of patients ten years after transplant.<a class="elsevierStyleCrossRef" href="#bib0180">3</a>Several studies in patients including biopsies performed periodically have shown that some parameters of measurement of kidney function (e.g., creatinine) underestimate the severity of CKD. Therefore, biopsies are an essential tool for an accurate diagnosis of CKD.<a class="elsevierStyleCrossRefs" href="#bib0180">3,4</a>The gradual deterioration of the kidney function is often accompanied by complications related to the presence of kidney failure (proteinuria, high blood pressure, diabetes, hyperlipidemia, anemia, metabolic acidosis, hyperphosphatemia, etc.).<a class="elsevierStyleCrossRefs" href="#bib0190">5–7</a> As it has been shown in several cohort studies of KT. Many patients with CKD have accelerated risk of deterioration of KT function as a consequence of these comorbidities.<a class="elsevierStyleCrossRef" href="#bib0205">8</a> The adequate treatment for these complications and the prevention CKD progression require more attention by the nephrologists.<a class="elsevierStyleCrossRef" href="#bib0205">8</a> As an example, in CKD associated tone phrotoxicity induced by calcineurin inhibitors (CNI), the possibility of reduced exposure by means of decreasing the dosage of CNI, or even discontinuation if possible, must be considered.<a class="elsevierStyleCrossRef" href="#bib0210">9</a>The objective of this study was to assess the nephrologist's clinical approach to kidney dysfunction in kidney transplant patients subjected to maintenance treatment. Additionally, it was assessed the treatment and control of markers and factors that favors progression of kidney dysfunction, such as hypertension, urine protein and anemia, and the presence of cardiovascular risk factors in these patients.Patients and methodsA non-interventional, multicentre, national and prospective study was carried out, with a follow-up period of six months. Initially, 446 adult kidney transplant recipients in maintenance treatment were included, between March 2009 and March 2010. Of these, 368 were ultimately included for final assessment in this study.Patients included had to be recipients of a simple kidney transplant, adult, with CKD-3 grade 3 according to the new guidelines K/DOQI, Kidney/Disease Outcomes Quality Initiative (glomerular filtration rate, GF of 30–59ml/min), having completed a minimum period of 24 months of transplantation, and having granted their consent to participate in the study. The K/DOQI guidelines recommend an estimation of the glomerular filtration rate with the MDRD formula.<a class="elsevierStyleCrossRef" href="#bib0215">10</a> The exclusion criteria were: presence of dual or multiorganic kidney transplant recipients, and chronic kidney disease of grade 3 (Banff scale) according to kidney graft biopsy.Schedule of visits included a retrospective visit (between 6 and 9 months earlier), a starting visit (month 0), an optional intermediate visit and a final visit (month 6). All patients signed the informed consent to participate in the study. A Clinical Research Ethics Committee authorized the study, which was carried out according to the Declaration of Helsinki.The information included in the present study was obtained by means of personal interviews with the patient and data collection from clinical history in 47 outpatient kidney transplant clinics from hospitals in Spain. The information of interest was: demographic data of patients and their medical history, aetiology of the terminal kidney failure (TKF), cardiovascular risk factors prior transplantation, clinical evolution of the transplant, age and sex of the donor, level of CKD analysed retrospectively, and at initial, intermediate (optional) and final visits, presence of secondary markers of CKD (proteinuria, serum creatinine level, GFR, blood pressure, haemoglobin level), blood analysis data, induction t and immunosuppression treatment at discharge.Additionally, a detailed history was obtained after transplantation, including information about clinical data of interest after transplantation (i.e., acute rejection, diabetes, hypertension and malignancies), diagnosis of CKD, kidney biopsies performed, immunosuppression and other medications. Further, treatment of comorbidites was also recorded. During the final visit, information was gathered about the morbidity and mortality of the patient during the study period.The objective criteria to assess the control of comorbidities was based on according to the corresponding guidelines of reference: diabetes (blood sugar level while fasting <120mg/dl)<a class="elsevierStyleCrossRef" href="#bib0220">11</a>; hypertension (blood pressure <130/85mmHg)<a class="elsevierStyleCrossRef" href="#bib0225">12</a>; mineral metabolism (Ca: 8.4–9.5mg/dl, P: 2.7–4.6mg/dl, iPTH<6.5pg/ml)<a class="elsevierStyleCrossRef" href="#bib0230">13</a>; hypercholesterolemia (LDL cholesterol<100mg/dl and HDL>40mg/dl in males and >46mg/dl in females); hypertriglyceridemia ≤200mg/dl).<a class="elsevierStyleCrossRef" href="#bib0235">14</a> Finally, an questionnaire was given to the nephrologists to provide an opinion about the changes they made in the immunosuppression therapy so the clinical approach of the physician could be assessed.Statistical analysisA descriptive analysis was made of the initial demographic and clinical variables of all the patients included in the study. The prevalence and the 95% confidence interval (CI) associated with the qualitative variables were calculated in the retrospective, initial, intermediate and final visits. This serve to compare frequencies and means between variables. The Kappa coefficient was used to assess the concordance between the diagnostic criteria established according to the clinical criteria and according to the objective functional criteria for the CKD markers.Student's t test, ANOVA for repeated measurements or Wilcoxon test, was used depending on the characteristics of each variable. McNemar's test was used for comparisons of qualitative variables.A multiple regression analysis was used to determine the factors that predict of worsening of GFR. This analysis was based on patients showing a GFR ≥10% in relation to the initial visit (n=67). In the multiple regression analysis, all the demographic and clinical variables which were close to statistical significance in prior univariate regressions (p<0.1) were included. A logistic procedure was used to extract the variability step by step, with goodness-of-fit assessment by means of the Hosmer and Lemeshow tests.The data were analyzed using the version 9.1 or later of the statistical software SAS.ResultsOut of the initial sample of 446 identified patients, a total of 368 patients with CKD of grade 3 (82.51%) met all the inclusion criteria and none of the exclusion criteria, and were finally included in the analysis of the present work.Demographic and descriptive dataMean age of patients was 55.6±12.9 years and 61.7% were males (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The average time since kidney transplant was 8.2±5.4 years. The most frequent case of terminal kidney failure (TKF) was chronic glomerulonephritis, which was observed in 114 cases (31.0%), whereas only one patient (0.3%) was found to have nephrotoxicity. Hypertension (80.2%) followed by anemia (34.5%) were the most frequent cardiovascular risk factors before transplantation; other risk factors were dyslipidemia (22.8%) and prior cardiovascular disease (3.5%).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Kidney function and other clinical assessmentThe initial serum creatinine concentration and the glomerular filtrate (GFR) were 1.6±0.3mg/l and 43.6±7.6ml/m, respectively. At the time of inclusion, 24h urine protein collected was 425.7±639.9mg (25.5% of patients had more than 300mg), 39.7% of patients presented anemia, 89.7% hypertension and 26.1% diabetes.A statistically significant increase in serum creatinine (0.06±0.22mg/dl, p<0.0001) was observed from the initial to month 6 visit. In the case of GFR, the difference was −1.03±6.14ml/min (p=0.0014) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). From initial visit and month 6 a reduction of GFR of more than 18% was observed in18.2% of patients. Nephropathy from BK virus was investigated in 32.6% of patients.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Neoplasia was diagnosed in 9.8% (n=36) of transplanted patients and the immunosuppression therapy was modified in 26 patients (72.2%). A.14.7% of patients (n=54) experienced cardiovascular complications: most frequent complication was angina (27.8%),, peripheral arterial disease was observed in 22.2%.Immunosuppression treatment and biopsiesTreatment for proteinuria, anemia and hypertension was set in 34.2%, 34.0% and 86.4% of patients and the treatment was strengthened in 60–73% of the uncontrolled patients. Despite treatment, at month 6, 26.1%, 7.3% and 64.7% of patients did not meet the treatment objectives for proteinuria, anemia and hypertension respectively. During follow-up, no significant changes were observed in the treatment for immunosuppression (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The most frequently used immunosuppression drug was calcineurin inhibitors (CNI) combined with anti-metabolites and esteroids.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>A biopsy was performed after transplantion in 28 patients (7.6%), and the most frequent finding was chronic rejection (n=8). The biopsy led to modification of therapy in 25.4% of cases; change in immunosuppression was the most frequent intervention (50.0%). In 83.3% of patients kidney function stabilize after modification of treatment. The biopsy was prescribed following clinical criteria in all cases, and according to the opinion of the physicians the biopsy was useful in 88.9% of cases. Physicians also considered that the techniques of immunohistochemistry and immunofluorescence were very useful to decide therapeutic strategies directed to stabilise kidney function (88.9% of cases).Clinical approach of doctorsThe nephrologist questionnaire shows that 88.1% of doctors used the level of proteinuria as a CKD marker, and more than 58% used anemia and hypertension in the same way. In addition, 80.6% of doctors calculated the change of GFR during the last year to assess the kidney function deterioration. Doctors have identified hypertension, dyslipidaemia, and hyperglycaemia as equally and clinically adequate factors to assess the evolution of CKD (91.7%; 91.7% and 88.9%; respectively). In the case of hypertension, most patients had a reduction of anti-calcineurin and an increase in mycophenolate (58.3%) with reduction or discontinuation of esteroids (both 66.7%). In the case of hyperglycaemia, the priority change was the reduction of treatment with esteroids (88.3%) or its interruption (80.6%). Finally, in the case of dyslipidaemia, the priority change was the reduction of treatment with esteroids (83.3%), and its interruption in 83.3% of cases.A 80.6% of the doctors considered that the kidney transplant recipients with CKD required a more intense control of cardiovascular risk factors, with blood more frequent biochemistries and echocardiograms.With regard to the control of secondary markers of CKD, there were no significant differences in hypertension (p=0.513), nor in the urine protein rates or of urine protein 24h (p=0.879) between patients during the visits.Prognostic factors of GF worseningThe model of multivariate logistic regression (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) showed that the significant independent prognostic factors of GFR worsening were: 24h proteinuria (OR=1.001 per each mg, p=0.020), period of time elapsed since transplantation (OR=1.009 per each month, p=0.017) and low haemoglobin (Hb)evel (OR=1.261 per each g/dl, p=0.038). Also, a negative influence of the donor's age was observed (OR=1.021 per each year, p=0.106).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Management of CKDIn the initial visit, approximately one third of the patients had an appropriate management of proteinuria, 89.3% in had controlled hypertension, and only 37.7% received optimal treatment of anemia. Physicians failed to treat proteinuria, hypertension and anemiain 31.3%, 18.6% and 16.7% of the cases respectively.In the initial visit, there was a 27.3% of patients with good control of mineral metabolism, 20.3% with acceptable control of diabetes and 72.9% with controlled cholesterol. In the final visit at month 6, only 16 patients had no appropriate control of mineral metabolism parameters; 37.5% of patients and an intensified control of these parameters. In the case of diabetes and hypercholesterolemia, there was an intensification of control in approximately 65% of the previously uncontrolled patients.The cardiovascular risk factors such as glucose, glycosylated haemoglobin, blood sugar levels, HDL cholesterol, LDL cholesterol, total cholesterol and triglycerides, remained stable throughout all the visits.There is disparity between the clinical perception and the objective parameters, which leads to a clear clinical inertia with respect to control of associated risk factors, hypertension and proteinuria (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Regarding hypertension, the perception of good control by the doctor was greater than the actual objective parameters gathered from the patient sheet (81.3% compared to 29.7%). Therefore, the Kappa coefficient of concordance was quite low and non-significant, with values between 0.0762 in the initial visit and 0.1438 in the final visit.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The perception of good control of proteinuria by doctors was greater (82.3%) than the objective parameters (49.2%). In this case, the coincidence between clinical perception and the objective parameters was greater than in hypertension, with a Kappa coefficient close to 0.5 in all visits.Finally, the clinical perception of good control of anemia corresponded almost completely with the objective criteria (85.1% compared to 89.1%); the coincidence increased between the retrospective and the final visits.A 15–32% of patients who needed initial treatment for hypertension and proteinuria were not objectively controlled.All patients were subjected to changes in their treatment and to another visit after the transplant. The main reason for changes in the treatment was the presence of comorbidities (12.5%). Different specialists were consulted in 14.1% of cases, mostly endocrinologists. An additional unforeseen visit was scheduled in25.8% of patients. In the final visit, a Doppler ultrasound of the transplanted kidney was performed in 4 patients, and there were 13 transplant obtained.DiscussionWe have carried out a non-interventional, prospective study to assess the clinical approach of doctors in the treatment of patients with CKD maintained with a kidney transplant in Spain.Our main results show that hypertension and anemia are the most frequent cardiovascular risk factors observed before transplantation. We also show that there are secondary markers of CKD that cannot be controlled after transplantation, mainly anemia, which persists without adequate treatment. Actually, our data shows that there is a 16.7% of patients without intensified treatment for anemia and this represents a considerable clinical inertia with major implications in the progression of CKD, with a low initial rate of adequate treatment of anemia (37.7%). This situation is similar to that observed in recent prospective studies, showing that the control of haemoglobin values reduces the progression of chronic kidney disease in allotransplant KT patients.<a class="elsevierStyleCrossRefs" href="#bib0240">15,16</a>A biopsy was obtained only in a limited number of cases of KT recipients with CKD grade 3, this is in contrast with recent data published suggesting the need for biopsies in these type of.<a class="elsevierStyleCrossRefs" href="#bib0180">3,4,17</a> The biopsy results led to therapeutic intervention in only 25.4% of patients who underwent this procedure, a percentage which may be considered low according to recent recommendations.<a class="elsevierStyleCrossRef" href="#bib0250">17</a>Several studies evaluating results from kidney biopsies have shown that the use of serum creatinine concentration for the diagnosis of nephropathy may lead to underestimation of the severity of CKD.<a class="elsevierStyleCrossRef" href="#bib0255">18</a> According to some authors, biopsy is a procedure recommended in patients with serum creatinine concentrations increased by more than 20% of the minimum creatinine concentration during the last 3–6 months, regardless of the presence of proteinuria.<a class="elsevierStyleCrossRef" href="#bib0260">19</a>In our study, a graft biopsy was performed in 7.6% of patients between the initial and final visit, and the most frequent cause was chronic rejection. Some studies have found an acute subclinical rejection in the evaluation of pre-scheduled biopsies in patients with CKD in early stages after transplantation. This finding predicts a lower survival of the transplant.<a class="elsevierStyleCrossRef" href="#bib0265">20</a> A recent controlled and randomised study showed that early treatment for rejection improved the clinical outcome of these patients.<a class="elsevierStyleCrossRef" href="#bib0270">21</a> Therefore, a more precise knowledge of the causes of CKD is required so an early diagnosis and treatment can be applied. Therefore, biopsies should perform before the patient evolves to advanced CKD.Some results conclude that an early biopsy that allows microscopic evaluation and appropriate changes in immunosuppressive treatment may be helpful in protecting the graft function.<a class="elsevierStyleCrossRef" href="#bib0270">21</a>The recent cross-sectional ICEBERG<a class="elsevierStyleCrossRef" href="#bib0275">22</a> study has shown that the prevalence of CKD in kidney transplant recipients is ranges from 35 and 55% depending on the diagnostic method, clinical or objective criteria such as serum creatinine or GFR. This study has also shown that CKD is a usually under-diagnosed pathology in maintenance KT recipients. Doctors only detect CKD in 4 out of the 10 patients that were diagnosed objectively. Further, the results of OBSERVA confirm that due to this under-diagnosis, most transplanted patients do not receive sufficient treatment for comorbidities. Therefore, regarding patients treatment there are considerable differences between the clinical perceptions and the objective parameters and this leads to significant clinical inertia. Avoiding this clinical inertia would be crucial in preserving kidney transplantfunction by modifying the CNI if needed, performing timely biopsy, adaptation of the immunosuppression therapy, treatment to the CKD, control of comorbidities, and the addition of recommendations for a healthy life style.<a class="elsevierStyleCrossRef" href="#bib0280">23</a>Further, we have observed that there is a large percentage of patients with uncontrolled hypertension, which may contribute to the increase of cardiovascular comorbidity and comortality of the transplant recipients. More intense treatment is required to improve the survival of the transplant and the patients. According to current recommendations at the time of the study, the optimum control of hypertension would be a blood pressure <130/80mmHg or <125/75 in patients with urine protein.<a class="elsevierStyleCrossRef" href="#bib0285">24</a> These authors suggest a strict control of hypertension to avoid clinical inertia in the kidney transplant centers. Other authors also suggest that reduced GF does not represent the total risk of presenting CKD, which suggests that there are other factors, such as asymptomatic cardiopathy, which could be involved in the gradual worsening of kidney function and in the transplant failure.<a class="elsevierStyleCrossRef" href="#bib0290">25</a> Likewise, recent studies carried out in the US have stressed the fact that there is still an opportunity to improve the treatment and control of traditional factors of cardiovascular risk in kidney transplant recipients, as suggested by the high rates of uncontrolled hypertension in these patients.<a class="elsevierStyleCrossRefs" href="#bib0295">26,27</a>Recent studies on kidney transplant recipients have shown that there is poor control of cardiovascular risk factors. In these studies, large differences have been observed in the treatment of kidney transplant and non-transplanted patients with the same stage of CKD.<a class="elsevierStyleCrossRefs" href="#bib0305">28,29</a> As compared with non-transplanted CKD patients, kidney transplant recipients show a poor control of blood pressure, lipids, and haemoglobin concentration. This data suggests that an adequate control of these parameters is not achieved in the outpatient KT.The KDIGO guidelines also provide suggestions for the effective control of serum creatinine and proteinuria.<a class="elsevierStyleCrossRefs" href="#bib0315">30,31</a> The level of serum creatinine one year after transplantion predicts poor outcome and may help determine the frequency of visits in long term care. Proteinuria has been associated with cardiovascular complications and mortality in KT patients. Therefore, the proteinuria measurement is recommended one month after transplantation as an initial value, and, every 3 months during the first year, and annually thereafter.<a class="elsevierStyleCrossRef" href="#bib0325">32</a> It is further recommended to treat proteinuria with renin–angiotensin inhibitors in an attempt to reduce chronic kidney disease.<a class="elsevierStyleCrossRef" href="#bib0330">33</a>Our study has several strong points, such as the large number of patients and participating centres, which represents the population of kidney transplant patients in Spain, and it reflect the treatment of these patients in every day clinical practice. Our study also has limitations, such as the short follow-up period after the kidney transplant, only 6 months. However, in patients with CKD grade 3, a follow-up of 6 months should be enough to allow the result of specific medical interventions directed to reduce worsening kidney function. Further, among the limitations, it should be noted that among the causes for progression of kidney failure, immunologic damage was not included, although it is not the objective of this study, which attempts to assess the clinical inertia in pathologies where action is still possible by following the guidelines available.In short, besides the treatment of proteinuria with renin–angiotensin blockers, it is necessary a more rigorous control other CKD markers, with assessment of biopsies, long term follow-up, and specific strategies for the control of comorbidity factors, to improve the clinical outcome and the survival of maintenance kidney transplant recipients.<a class="elsevierStyleCrossRef" href="#bib1300">34</a>Conflict of interestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres576992" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec593621" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres576993" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec593620" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0020" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Demographic and descriptive data" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Kidney function and other clinical assessment" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Immunosuppression treatment and biopsies" ] 3 => array:2 [ "identificador" => "sec0070" "titulo" => "Clinical approach of doctors" ] 4 => array:2 [ "identificador" => "sec0075" "titulo" => "Prognostic factors of GF worsening" ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "Management of CKD" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-07-14" "fechaAceptado" => "2014-12-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec593621" "palabras" => array:3 [ 0 => "Renal transplantation" 1 => "Chronic kidney disease management" 2 => "Clinical attitude" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec593620" "palabras" => array:3 [ 0 => "Trasplante renal" 1 => "Tratamiento de la disfunción renal crónica" 2 => "Actitud clínica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Background and objectivesIn the present study, clinical criteria used by Spanish nephrologists when approaching chronic kidney disease (CKD) in kidney recipients, as well as their level of maintenance and control of renal function, were evaluated. MethodsAn epidemiological, observational, multicenter, nation-wide, prospective study was carried out, with a 6-month follow-up period. Three hundred and sixty-eight adult patients with stage 3 kidney disease after a 24-month or longer post-transplantation follow-up period were included. Visits schedule included a retrospective visit, a baseline visit, an optional mid-term visit, and a final visit at month 6. ResultsMean time since kidney transplantation was 8.2±5.4years. Most common pre-transplant cardiovascular risk factors were high blood pressure (80.2%), followed by high cholesterol levels (61.7%). Serum creatinine levels showed a statistically significant decrease from baseline visit to 6-month visit (0.06±0.22; p<.0001), and glomerular filtration rate (GFR) reduction was −1.03±6.14 (p=0.0014). Significant independent prognostic factors for GFR worsening were: higher 24-h proteinuria (OR=1.001 per mg; p=.020), longer time since transplantation (OR=1.009 per month; p=.017), and lower hemoglobin levels (OR=1.261 per g/dl; p=.038). Donor age also had some negative influence (OR=1.021 per year; p=.106). Biopsies were obtained in only 8% of kidney transplant recipients with stage 3 CKD with an intervention being carried out in 25.4% of cases. ConclusionsSecondary markers and factors resulting in CKD progression, particularly anemia, are still frequently uncontrolled after kidney transplantation. Only about 2% of patients benefit from a therapeutic intervention based on a biopsy. Clinical perception differs from objective measures, which results in an obvious clinical inertia regarding risk factor control in such patients." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "Antecedentes y objetivosEl presente estudio ha evaluado el criterio clínico que utilizan los nefrólogos españoles frente a la disfunción renal crónica (DRC) en receptores de trasplante renal (TR), y el grado de mantenimiento y control de la disfunción renal. MétodosEstudio observacional, epidemiológico, multicéntrico, nacional y prospectivo, con un período de seguimiento de 6meses. Se incluyeron 368 pacientes adultos con disfunción renal de grado3 con un período mínimo de evolución posterior al trasplante de 24meses. La programación de las visitas incluyó una visita retrospectiva, una visita inicial, una visita intermedia opcional y una visita final al sexto mes. ResultadosEl tiempo medio desde el TR fue de 8,2±5,4años. La hipertensión (80,2%), seguida por la hipercolesterolemia (61,7%), fueron los factores de riesgo cardiovascular previos al trasplante más frecuentes. Las concentraciones de creatinina sérica entre la visita inicial y la visita de los 6meses mostraron una diferencia estadísticamente significativa de 0,06±0,22 (p<0,0001), y la diferencia del filtrado glomerular (FG) fue de −1,03±6,14 (p=0,0014). Los factores pronósticos independientes significativos del empeoramiento del FG fueron: proteinuria a 24h más alta (OR=1,001 por cada mg; p=0,020), más tiempo desde el trasplante (OR=1,009 por cada mes; p=0,017) y concentraciones bajas de hemoglobina (OR=1,261 por cada g/dl; p=0,038). También se observó cierta influencia negativa de la edad del donante (OR=1,021 por cada año; p=0,106). Solo se realizó biopsia en el 8% de los casos de receptores de TR con DRC de grado 3, suponiendo alguna intervención en el 25,4% de los casos. ConclusionesCon frecuencia los marcadores secundarios y los factores de progresión de la DRC siguen sin estar controlados después del TR, principalmente la anemia. Solo aproximadamente el 2% de pacientes se benefician de una intervención terapéutica basada en una biopsia. Existe una disparidad entre la percepción clínica y los parámetros objetivos, que conduce a una clara inercia clínica del control de los factores de riesgo de estos pacientes." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Campistol JM, Gutiérrez-Dalmau A, Crespo J, Saval N, Grinyó JM. Actitud clínica frente a la disfunción renal en receptores de un trasplante renal en España. Nefrologia. 2015;35:256–263." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2236 "Ancho" => 1660 "Tamanyo" => 200003 ] ] "descripcion" => array:1 [ "en" => "Evolution of renal function." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1285 "Ancho" => 2694 "Tamanyo" => 226068 ] ] "descripcion" => array:1 [ "en" => "Changes in immunosuppressive treatment." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1694 "Ancho" => 2965 "Tamanyo" => 339040 ] ] "descripcion" => array:1 [ "en" => "Significant independent prognostic factors of deterioration of glomerular filtration rate." ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Abbreviations: SD: standard deviation, PRA: profile of reactive antibodies; HLA: Human Leukocyte Antigen." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Kidney recipients</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Gender, male (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">227 (61.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age (years), mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55.6 (12.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Donor</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Gender, male (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">211 (57.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age (years), mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.5 (16.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Time since transplant</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean (±SD), years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.2±5.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">First transplant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">297 (80.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Second transplant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 (16.3%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Third transplant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (1.1%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">PAR prior to transplant</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">281 (76.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Between 0 and 10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 (5.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Between 10% and 20% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (1.6%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">20% or more \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 (4.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">No. of HLA incompatibilities</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (0.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (3.8%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 (16.0%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">102 (27.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">132 (35.9%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 (13.6%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (2.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Cardiovascular risk factors (CVRF)</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">High blood pressure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">295 (80.2%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hypercholesterolaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">227 (61.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Urine protein \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">161 (43.8%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">127 (34.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Obesity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">104 (28.3%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hypertriglyceridaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85 (23.1%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Diabetes mellitus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82 (22.3%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Patients with ≥1 CVRF prior to transplant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">331 (90.0%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab942022.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Initial characteristics of the sample." ] ] 4 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Good control according to objective parameters or confirmed: PAS/PAD<130/80mmHg; urine protein 24h ≤300mg/24h; hemoglobin>11g/dl." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Final visit (month 6) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">High blood pressure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Good control according to doctor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">81.3% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Good control according to objective parameters \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.6% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Urine protein \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Good control according to doctor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82.3% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Good control according to objective parameters \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49.2% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Good control according to doctor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85.1% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Good control according to objective parameters \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">89.1% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab942023.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Degree of control of risk factors of kidney dysfunction (hypertension, urine protein and anemia) in the final visit." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:34 [ 0 => array:3 [ "identificador" => "bib0170" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic allograft nephropathy: current concepts and future directions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B.J. 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Actitud clínica frente a la disfunción renal en receptores de un trasplante renal en España

Josep M. Campistola, Alex Gutiérrez-Dalmaub, Josep Crespoc, Núria Savald, Josep Maria Grinyóe,

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jgrinyo@bellvitgehospital.cat

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, Grupo de Estudio Observa

a Unidad de Nefrología y Trasplante Renal, Hospital Clínic, Barcelona, Spain

b Servicio de Nefrología, Hospital Miguel Servet, Zaragoza, Spain

c Servicio de Nefrología, Hospital Universitario Dr. Peset, Valencia, Spain

d Novartis Farmacéutica S.A., Barcelona, Spain

e Unidad de Nefrología y Trasplante Renal, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain

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presence of dual or multiorganic kidney transplant recipients&#44; and chronic kidney disease of grade 3 &#40;Banff scale&#41; according to kidney graft biopsy&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Schedule of visits included a retrospective visit &#40;between 6 and 9 months earlier&#41;&#44; a starting visit &#40;month 0&#41;&#44; an optional intermediate visit and a final visit &#40;month 6&#41;&#46; All patients signed the informed consent to participate in the study&#46; A Clinical Research Ethics Committee authorized the study&#44; which was carried out according to the Declaration of Helsinki&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">The information included in the present study was obtained by means of personal interviews with the patient and data collection from clinical history in 47 outpatient kidney transplant clinics from hospitals in Spain&#46; The information of interest was&#58; demographic data of patients and their medical history&#44; aetiology of the terminal kidney failure &#40;TKF&#41;&#44; cardiovascular risk factors prior transplantation&#44; clinical evolution of the transplant&#44; age and sex of the donor&#44; level of CKD analysed retrospectively&#44; and at initial&#44; intermediate &#40;optional&#41; and final visits&#44; presence of secondary markers of CKD &#40;proteinuria&#44; serum creatinine level&#44; GFR&#44; blood pressure&#44; haemoglobin level&#41;&#44; blood analysis data&#44; induction t and immunosuppression treatment at discharge&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Additionally&#44; a detailed history was obtained after transplantation&#44; including information about clinical data of interest after transplantation &#40;i&#46;e&#46;&#44; acute rejection&#44; diabetes&#44; hypertension and malignancies&#41;&#44; diagnosis of CKD&#44; kidney biopsies performed&#44; immunosuppression and other medications&#46; Further&#44; treatment of comorbidites was also recorded&#46; During the final visit&#44; information was gathered about the morbidity and mortality of the patient during the study period&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The objective criteria to assess the control of comorbidities was based on according to the corresponding guidelines of reference&#58; diabetes &#40;blood sugar level while fasting &#60;120<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">11</span></a>&#59; hypertension &#40;blood pressure &#60;130&#47;85<span class="elsevierStyleHsp" style=""></span>mmHg&#41;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a>&#59; mineral metabolism &#40;Ca&#58; 8&#46;4&#8211;9&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; P&#58; 2&#46;7&#8211;4&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; iPTH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>6&#46;5<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">13</span></a>&#59; hypercholesterolemia &#40;LDL cholesterol<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>mg&#47;dl and HDL<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>mg&#47;dl in males and &#62;46<span class="elsevierStyleHsp" style=""></span>mg&#47;dl in females&#41;&#59; hypertriglyceridemia &#8804;200<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">14</span></a> Finally&#44; an questionnaire was given to the nephrologists to provide an opinion about the changes they made in the immunosuppression therapy so the clinical approach of the physician could be assessed&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0275" class="elsevierStylePara elsevierViewall">A descriptive analysis was made of the initial demographic and clinical variables of all the patients included in the study&#46; The prevalence and the 95&#37; confidence interval &#40;CI&#41; associated with the qualitative variables were calculated in the retrospective&#44; initial&#44; intermediate and final visits&#46; This serve to compare frequencies and means between variables&#46; The Kappa coefficient was used to assess the concordance between the diagnostic criteria established according to the clinical criteria and according to the objective functional criteria for the CKD markers&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Student&#39;s <span class="elsevierStyleItalic">t</span> test&#44; ANOVA for repeated measurements or Wilcoxon test&#44; was used depending on the characteristics of each variable&#46; McNemar&#39;s test was used for comparisons of qualitative variables&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">A multiple regression analysis was used to determine the factors that predict of worsening of GFR&#46; This analysis was based on patients showing a GFR &#8805;10&#37; in relation to the initial visit &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>67&#41;&#46; In the multiple regression analysis&#44; all the demographic and clinical variables which were close to statistical significance in prior univariate regressions &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#41; were included&#46; A logistic procedure was used to extract the variability step by step&#44; with goodness-of-fit assessment by means of the Hosmer and Lemeshow tests&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The data were analyzed using the version 9&#46;1 or later of the statistical software SAS&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0285" class="elsevierStylePara elsevierViewall">Out of the initial sample of 446 identified patients&#44; a total of 368 patients with CKD of grade 3 &#40;82&#46;51&#37;&#41; met all the inclusion criteria and none of the exclusion criteria&#44; and were finally included in the analysis of the present work&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Demographic and descriptive data</span><p id="par0095" class="elsevierStylePara elsevierViewall">Mean age of patients was 55&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;9 years and 61&#46;7&#37; were males &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The average time since kidney transplant was 8&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;4 years&#46; The most frequent case of terminal kidney failure &#40;TKF&#41; was chronic glomerulonephritis&#44; which was observed in 114 cases &#40;31&#46;0&#37;&#41;&#44; whereas only one patient &#40;0&#46;3&#37;&#41; was found to have nephrotoxicity&#46; Hypertension &#40;80&#46;2&#37;&#41; followed by anemia &#40;34&#46;5&#37;&#41; were the most frequent cardiovascular risk factors before transplantation&#59; other risk factors were dyslipidemia &#40;22&#46;8&#37;&#41; and prior cardiovascular disease &#40;3&#46;5&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Kidney function and other clinical assessment</span><p id="par0100" class="elsevierStylePara elsevierViewall">The initial serum creatinine concentration and the glomerular filtrate &#40;GFR&#41; were 1&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and 43&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;6<span class="elsevierStyleHsp" style=""></span>ml&#47;m&#44; respectively&#46; At the time of inclusion&#44; 24<span class="elsevierStyleHsp" style=""></span>h urine protein collected was 425&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>639&#46;9<span class="elsevierStyleHsp" style=""></span>mg &#40;25&#46;5&#37; of patients had more than 300<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; 39&#46;7&#37; of patients presented anemia&#44; 89&#46;7&#37; hypertension and 26&#46;1&#37; diabetes&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">A statistically significant increase in serum creatinine &#40;0&#46;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;22<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; was observed from the initial to month 6 visit&#46; In the case of GFR&#44; the difference was &#8722;1&#46;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;14<span class="elsevierStyleHsp" style=""></span>ml&#47;min &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0014&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; From initial visit and month 6 a reduction of GFR of more than 18&#37; was observed in18&#46;2&#37; of patients&#46; Nephropathy from BK virus was investigated in 32&#46;6&#37; of patients&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Neoplasia was diagnosed in 9&#46;8&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>36&#41; of transplanted patients and the immunosuppression therapy was modified in 26 patients &#40;72&#46;2&#37;&#41;&#46; A&#46;14&#46;7&#37; of patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>54&#41; experienced cardiovascular complications&#58; most frequent complication was angina &#40;27&#46;8&#37;&#41;&#44;&#44; peripheral arterial disease was observed in 22&#46;2&#37;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Immunosuppression treatment and biopsies</span><p id="par0290" class="elsevierStylePara elsevierViewall">Treatment for proteinuria&#44; anemia and hypertension was set in 34&#46;2&#37;&#44; 34&#46;0&#37; and 86&#46;4&#37; of patients and the treatment was strengthened in 60&#8211;73&#37; of the uncontrolled patients&#46; Despite treatment&#44; at month 6&#44; 26&#46;1&#37;&#44; 7&#46;3&#37; and 64&#46;7&#37; of patients did not meet the treatment objectives for proteinuria&#44; anemia and hypertension respectively&#46; During follow-up&#44; no significant changes were observed in the treatment for immunosuppression &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The most frequently used immunosuppression drug was calcineurin inhibitors &#40;CNI&#41; combined with anti-metabolites and esteroids&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0295" class="elsevierStylePara elsevierViewall">A biopsy was performed after transplantion in 28 patients &#40;7&#46;6&#37;&#41;&#44; and the most frequent finding was chronic rejection &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#46; The biopsy led to modification of therapy in 25&#46;4&#37; of cases&#59; change in immunosuppression was the most frequent intervention &#40;50&#46;0&#37;&#41;&#46; In 83&#46;3&#37; of patients kidney function stabilize after modification of treatment&#46; The biopsy was prescribed following clinical criteria in all cases&#44; and according to the opinion of the physicians the biopsy was useful in 88&#46;9&#37; of cases&#46; Physicians also considered that the techniques of immunohistochemistry and immunofluorescence were very useful to decide therapeutic strategies directed to stabilise kidney function &#40;88&#46;9&#37; of cases&#41;&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Clinical approach of doctors</span><p id="par0300" class="elsevierStylePara elsevierViewall">The nephrologist questionnaire shows that 88&#46;1&#37; of doctors used the level of proteinuria as a CKD marker&#44; and more than 58&#37; used anemia and hypertension in the same way&#46; In addition&#44; 80&#46;6&#37; of doctors calculated the change of GFR during the last year to assess the kidney function deterioration&#46; Doctors have identified hypertension&#44; dyslipidaemia&#44; and hyperglycaemia as equally and clinically adequate factors to assess the evolution of CKD &#40;91&#46;7&#37;&#59; 91&#46;7&#37; and 88&#46;9&#37;&#59; respectively&#41;&#46; In the case of hypertension&#44; most patients had a reduction of anti-calcineurin and an increase in mycophenolate &#40;58&#46;3&#37;&#41; with reduction or discontinuation of esteroids &#40;both 66&#46;7&#37;&#41;&#46; In the case of hyperglycaemia&#44; the priority change was the reduction of treatment with esteroids &#40;88&#46;3&#37;&#41; or its interruption &#40;80&#46;6&#37;&#41;&#46; Finally&#44; in the case of dyslipidaemia&#44; the priority change was the reduction of treatment with esteroids &#40;83&#46;3&#37;&#41;&#44; and its interruption in 83&#46;3&#37; of cases&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">A 80&#46;6&#37; of the doctors considered that the kidney transplant recipients with CKD required a more intense control of cardiovascular risk factors&#44; with blood more frequent biochemistries and echocardiograms&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">With regard to the control of secondary markers of CKD&#44; there were no significant differences in hypertension &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;513&#41;&#44; nor in the urine protein rates or of urine protein 24<span class="elsevierStyleHsp" style=""></span>h &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;879&#41; between patients during the visits&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Prognostic factors of GF worsening</span><p id="par0140" class="elsevierStylePara elsevierViewall">The model of multivariate logistic regression &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; showed that the significant independent prognostic factors of GFR worsening were&#58; 24<span class="elsevierStyleHsp" style=""></span>h proteinuria &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;001 per each mg&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;020&#41;&#44; period of time elapsed since transplantation &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;009 per each month&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;017&#41; and low haemoglobin &#40;Hb&#41;evel &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;261 per each g&#47;dl&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;038&#41;&#46; Also&#44; a negative influence of the donor&#39;s age was observed &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;021 per each year&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;106&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Management of CKD</span><p id="par0145" class="elsevierStylePara elsevierViewall">In the initial visit&#44; approximately one third of the patients had an appropriate management of proteinuria&#44; 89&#46;3&#37; in had controlled hypertension&#44; and only 37&#46;7&#37; received optimal treatment of anemia&#46; Physicians failed to treat proteinuria&#44; hypertension and anemiain 31&#46;3&#37;&#44; 18&#46;6&#37; and 16&#46;7&#37; of the cases respectively&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In the initial visit&#44; there was a 27&#46;3&#37; of patients with good control of mineral metabolism&#44; 20&#46;3&#37; with acceptable control of diabetes and 72&#46;9&#37; with controlled cholesterol&#46; In the final visit at month 6&#44; only 16 patients had no appropriate control of mineral metabolism parameters&#59; 37&#46;5&#37; of patients and an intensified control of these parameters&#46; In the case of diabetes and hypercholesterolemia&#44; there was an intensification of control in approximately 65&#37; of the previously uncontrolled patients&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">The cardiovascular risk factors such as glucose&#44; glycosylated haemoglobin&#44; blood sugar levels&#44; HDL cholesterol&#44; LDL cholesterol&#44; total cholesterol and triglycerides&#44; remained stable throughout all the visits&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">There is disparity between the clinical perception and the objective parameters&#44; which leads to a clear clinical inertia with respect to control of associated risk factors&#44; hypertension and proteinuria &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Regarding hypertension&#44; the perception of good control by the doctor was greater than the actual objective parameters gathered from the patient sheet &#40;81&#46;3&#37; compared to 29&#46;7&#37;&#41;&#46; Therefore&#44; the Kappa coefficient of concordance was quite low and non-significant&#44; with values between 0&#46;0762 in the initial visit and 0&#46;1438 in the final visit&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0315" class="elsevierStylePara elsevierViewall">The perception of good control of proteinuria by doctors was greater &#40;82&#46;3&#37;&#41; than the objective parameters &#40;49&#46;2&#37;&#41;&#46; In this case&#44; the coincidence between clinical perception and the objective parameters was greater than in hypertension&#44; with a Kappa coefficient close to 0&#46;5 in all visits&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Finally&#44; the clinical perception of good control of anemia corresponded almost completely with the objective criteria &#40;85&#46;1&#37; compared to 89&#46;1&#37;&#41;&#59; the coincidence increased between the retrospective and the final visits&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">A 15&#8211;32&#37; of patients who needed initial treatment for hypertension and proteinuria were not objectively controlled&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">All patients were subjected to changes in their treatment and to another visit after the transplant&#46; The main reason for changes in the treatment was the presence of comorbidities &#40;12&#46;5&#37;&#41;&#46; Different specialists were consulted in 14&#46;1&#37; of cases&#44; mostly endocrinologists&#46; An additional unforeseen visit was scheduled in25&#46;8&#37; of patients&#46; In the final visit&#44; a Doppler ultrasound of the transplanted kidney was performed in 4 patients&#44; and there were 13 transplant obtained&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0325" class="elsevierStylePara elsevierViewall">We have carried out a non-interventional&#44; prospective study to assess the clinical approach of doctors in the treatment of patients with CKD maintained with a kidney transplant in Spain&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Our main results show that hypertension and anemia are the most frequent cardiovascular risk factors observed before transplantation&#46; We also show that there are secondary markers of CKD that cannot be controlled after transplantation&#44; mainly anemia&#44; which persists without adequate treatment&#46; Actually&#44; our data shows that there is a 16&#46;7&#37; of patients without intensified treatment for anemia and this represents a considerable clinical inertia with major implications in the progression of CKD&#44; with a low initial rate of adequate treatment of anemia &#40;37&#46;7&#37;&#41;&#46; This situation is similar to that observed in recent prospective studies&#44; showing that the control of haemoglobin values reduces the progression of chronic kidney disease in allotransplant KT patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">15&#44;16</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">A biopsy was obtained only in a limited number of cases of KT recipients with CKD grade 3&#44; this is in contrast with recent data published suggesting the need for biopsies in these type of&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">3&#44;4&#44;17</span></a> The biopsy results led to therapeutic intervention in only 25&#46;4&#37; of patients who underwent this procedure&#44; a percentage which may be considered low according to recent recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Several studies evaluating results from kidney biopsies have shown that the use of serum creatinine concentration for the diagnosis of nephropathy may lead to underestimation of the severity of CKD&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a> According to some authors&#44; biopsy is a procedure recommended in patients with serum creatinine concentrations increased by more than 20&#37; of the minimum creatinine concentration during the last 3&#8211;6 months&#44; regardless of the presence of proteinuria&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">In our study&#44; a graft biopsy was performed in 7&#46;6&#37; of patients between the initial and final visit&#44; and the most frequent cause was chronic rejection&#46; Some studies have found an acute subclinical rejection in the evaluation of pre-scheduled biopsies in patients with CKD in early stages after transplantation&#46; This finding predicts a lower survival of the transplant&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a> A recent controlled and randomised study showed that early treatment for rejection improved the clinical outcome of these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">21</span></a> Therefore&#44; a more precise knowledge of the causes of CKD is required so an early diagnosis and treatment can be applied&#46; Therefore&#44; biopsies should perform before the patient evolves to advanced CKD&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">Some results conclude that an early biopsy that allows microscopic evaluation and appropriate changes in immunosuppressive treatment may be helpful in protecting the graft function&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">21</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">The recent cross-sectional ICEBERG<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">22</span></a> study has shown that the prevalence of CKD in kidney transplant recipients is ranges from 35 and 55&#37; depending on the diagnostic method&#44; clinical or objective criteria such as serum creatinine or GFR&#46; This study has also shown that CKD is a usually under-diagnosed pathology in maintenance KT recipients&#46; Doctors only detect CKD in 4 out of the 10 patients that were diagnosed objectively&#46; Further&#44; the results of OBSERVA confirm that due to this under-diagnosis&#44; most transplanted patients do not receive sufficient treatment for comorbidities&#46; Therefore&#44; regarding patients treatment there are considerable differences between the clinical perceptions and the objective parameters and this leads to significant clinical inertia&#46; Avoiding this clinical inertia would be crucial in preserving kidney transplantfunction by modifying the CNI if needed&#44; performing timely biopsy&#44; adaptation of the immunosuppression therapy&#44; treatment to the CKD&#44; control of comorbidities&#44; and the addition of recommendations for a healthy life style&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">23</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Further&#44; we have observed that there is a large percentage of patients with uncontrolled hypertension&#44; which may contribute to the increase of cardiovascular comorbidity and comortality of the transplant recipients&#46; More intense treatment is required to improve the survival of the transplant and the patients&#46; According to current recommendations at the time of the study&#44; the optimum control of hypertension would be a blood pressure &#60;130&#47;80<span class="elsevierStyleHsp" style=""></span>mmHg or &#60;125&#47;75 in patients with urine protein&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">24</span></a> These authors suggest a strict control of hypertension to avoid clinical inertia in the kidney transplant centers&#46; Other authors also suggest that reduced GF does not represent the total risk of presenting CKD&#44; which suggests that there are other factors&#44; such as asymptomatic cardiopathy&#44; which could be involved in the gradual worsening of kidney function and in the transplant failure&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> Likewise&#44; recent studies carried out in the US have stressed the fact that there is still an opportunity to improve the treatment and control of traditional factors of cardiovascular risk in kidney transplant recipients&#44; as suggested by the high rates of uncontrolled hypertension in these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">26&#44;27</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Recent studies on kidney transplant recipients have shown that there is poor control of cardiovascular risk factors&#46; In these studies&#44; large differences have been observed in the treatment of kidney transplant and non-transplanted patients with the same stage of CKD&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">28&#44;29</span></a> As compared with non-transplanted CKD patients&#44; kidney transplant recipients show a poor control of blood pressure&#44; lipids&#44; and haemoglobin concentration&#46; This data suggests that an adequate control of these parameters is not achieved in the outpatient KT&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">The KDIGO guidelines also provide suggestions for the effective control of serum creatinine and proteinuria&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">30&#44;31</span></a> The level of serum creatinine one year after transplantion predicts poor outcome and may help determine the frequency of visits in long term care&#46; Proteinuria has been associated with cardiovascular complications and mortality in KT patients&#46; Therefore&#44; the proteinuria measurement is recommended one month after transplantation as an initial value&#44; and&#44; every 3 months during the first year&#44; and annually thereafter&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">32</span></a> It is further recommended to treat proteinuria with renin&#8211;angiotensin inhibitors in an attempt to reduce chronic kidney disease&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Our study has several strong points&#44; such as the large number of patients and participating centres&#44; which represents the population of kidney transplant patients in Spain&#44; and it reflect the treatment of these patients in every day clinical practice&#46; Our study also has limitations&#44; such as the short follow-up period after the kidney transplant&#44; only 6 months&#46; However&#44; in patients with CKD grade 3&#44; a follow-up of 6 months should be enough to allow the result of specific medical interventions directed to reduce worsening kidney function&#46; Further&#44; among the limitations&#44; it should be noted that among the causes for progression of kidney failure&#44; immunologic damage was not included&#44; although it is not the objective of this study&#44; which attempts to assess the clinical inertia in pathologies where action is still possible by following the guidelines available&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall">In short&#44; besides the treatment of proteinuria with renin&#8211;angiotensin blockers&#44; it is necessary a more rigorous control other CKD markers&#44; with assessment of biopsies&#44; long term follow-up&#44; and specific strategies for the control of comorbidity factors&#44; to improve the clinical outcome and the survival of maintenance kidney transplant recipients&#46;<a class="elsevierStyleCrossRef" href="#bib1300"><span class="elsevierStyleSup">34</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interest</span><p id="par0245" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "titulo" => "Resumen"
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              "titulo" => "Antecedentes y objetivos"
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          "titulo" => "Palabras clave"
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          "titulo" => "Introduction"
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          "titulo" => "Patients and methods"
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          "titulo" => "Results"
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            0 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Demographic and descriptive data"
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            1 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Kidney function and other clinical assessment"
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              "identificador" => "sec0065"
              "titulo" => "Immunosuppression treatment and biopsies"
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              "titulo" => "Clinical approach of doctors"
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              "titulo" => "Prognostic factors of GF worsening"
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              "titulo" => "Management of CKD"
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    "fechaRecibido" => "2014-07-14"
    "fechaAceptado" => "2014-12-30"
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            0 => "Renal transplantation"
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            2 => "Clinical attitude"
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            0 => "Trasplante renal"
            1 => "Tratamiento de la disfunci&#243;n renal cr&#243;nica"
            2 => "Actitud cl&#237;nica"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In the present study&#44; clinical criteria used by Spanish nephrologists when approaching chronic kidney disease &#40;CKD&#41; in kidney recipients&#44; as well as their level of maintenance and control of renal function&#44; were evaluated&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">An epidemiological&#44; observational&#44; multicenter&#44; nation-wide&#44; prospective study was carried out&#44; with a 6-month follow-up period&#46; Three hundred and sixty-eight adult patients with stage 3 kidney disease after a 24-month or longer post-transplantation follow-up period were included&#46; Visits schedule included a retrospective visit&#44; a baseline visit&#44; an optional mid-term visit&#44; and a final visit at month 6&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Mean time since kidney transplantation was 8&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;4<span class="elsevierStyleHsp" style=""></span>years&#46; Most common pre-transplant cardiovascular risk factors were high blood pressure &#40;80&#46;2&#37;&#41;&#44; followed by high cholesterol levels &#40;61&#46;7&#37;&#41;&#46; Serum creatinine levels showed a statistically significant decrease from baseline visit to 6-month visit &#40;0&#46;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;22&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#44; and glomerular filtration rate &#40;GFR&#41; reduction was &#8722;1&#46;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;14 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0014&#41;&#46; Significant independent prognostic factors for GFR worsening were&#58; higher 24-h proteinuria &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;001 per mg&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;020&#41;&#44; longer time since transplantation &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;009 per month&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;017&#41;&#44; and lower hemoglobin levels &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;261 per g&#47;dl&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;038&#41;&#46; Donor age also had some negative influence &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;021 per year&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;106&#41;&#46; Biopsies were obtained in only 8&#37; of kidney transplant recipients with stage 3 CKD with an intervention being carried out in 25&#46;4&#37; of cases&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Secondary markers and factors resulting in CKD progression&#44; particularly anemia&#44; are still frequently uncontrolled after kidney transplantation&#46; Only about 2&#37; of patients benefit from a therapeutic intervention based on a biopsy&#46; Clinical perception differs from objective measures&#44; which results in an obvious clinical inertia regarding risk factor control in such patients&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El presente estudio ha evaluado el criterio cl&#237;nico que utilizan los nefr&#243;logos espa&#241;oles frente a la disfunci&#243;n renal cr&#243;nica &#40;DRC&#41; en receptores de trasplante renal &#40;TR&#41;&#44; y el grado de mantenimiento y control de la disfunci&#243;n renal&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional&#44; epidemiol&#243;gico&#44; multic&#233;ntrico&#44; nacional y prospectivo&#44; con un per&#237;odo de seguimiento de 6<span class="elsevierStyleHsp" style=""></span>meses&#46; Se incluyeron 368 pacientes adultos con disfunci&#243;n renal de grado<span class="elsevierStyleHsp" style=""></span>3 con un per&#237;odo m&#237;nimo de evoluci&#243;n posterior al trasplante de 24<span class="elsevierStyleHsp" style=""></span>meses&#46; La programaci&#243;n de las visitas incluy&#243; una visita retrospectiva&#44; una visita inicial&#44; una visita intermedia opcional y una visita final al sexto mes&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El tiempo medio desde el TR fue de 8&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;4<span class="elsevierStyleHsp" style=""></span>a&#241;os&#46; La hipertensi&#243;n &#40;80&#44;2&#37;&#41;&#44; seguida por la hipercolesterolemia &#40;61&#44;7&#37;&#41;&#44; fueron los factores de riesgo cardiovascular previos al trasplante m&#225;s frecuentes&#46; Las concentraciones de creatinina s&#233;rica entre la visita inicial y la visita de los 6<span class="elsevierStyleHsp" style=""></span>meses mostraron una diferencia estad&#237;sticamente significativa de 0&#44;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;22 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41;&#44; y la diferencia del filtrado glomerular &#40;FG&#41; fue de &#8722;1&#44;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;14 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0014&#41;&#46; Los factores pron&#243;sticos independientes significativos del empeoramiento del FG fueron&#58; proteinuria a 24<span class="elsevierStyleHsp" style=""></span>h m&#225;s alta &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;001 por cada mg&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;020&#41;&#44; m&#225;s tiempo desde el trasplante &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;009 por cada mes&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;017&#41; y concentraciones bajas de hemoglobina &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;261 por cada g&#47;dl&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;038&#41;&#46; Tambi&#233;n se observ&#243; cierta influencia negativa de la edad del donante &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;021 por cada a&#241;o&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;106&#41;&#46; Solo se realiz&#243; biopsia en el 8&#37; de los casos de receptores de TR con DRC de grado 3&#44; suponiendo alguna intervenci&#243;n en el 25&#44;4&#37; de los casos&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Con frecuencia los marcadores secundarios y los factores de progresi&#243;n de la DRC siguen sin estar controlados despu&#233;s del TR&#44; principalmente la anemia&#46; Solo aproximadamente el 2&#37; de pacientes se benefician de una intervenci&#243;n terap&#233;utica basada en una biopsia&#46; Existe una disparidad entre la percepci&#243;n cl&#237;nica y los par&#225;metros objetivos&#44; que conduce a una clara inercia cl&#237;nica del control de los factores de riesgo de estos pacientes&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Campistol JM&#44; Guti&#233;rrez-Dalmau A&#44; Crespo J&#44; Saval N&#44; Griny&#243; JM&#46; Actitud cl&#237;nica frente a la disfunci&#243;n renal en receptores de un trasplante renal en Espa&#241;a&#46; Nefrologia&#46; 2015&#59;35&#58;256&#8211;263&#46;</p>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations&#58;</span> SD&#58; standard deviation&#44; PRA&#58; profile of reactive antibodies&#59; HLA&#58; Human Leukocyte Antigen&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Kidney recipients</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Gender&#44; male &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">227 &#40;61&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#41;&#44; mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#46;6 &#40;12&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Donor</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Gender&#44; male &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">211 &#40;57&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#41;&#44; mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&#46;5 &#40;16&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Time since transplant</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean &#40;&#177;SD&#41;&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>First transplant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">297 &#40;80&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Second transplant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50 &#40;16&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Third transplant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;1&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">PAR prior to transplant</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">281 &#40;76&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Between 0 and 10&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20 &#40;5&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Between 10&#37; and 20&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;1&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>20&#37; or more&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16 &#40;4&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">No&#46; of HLA incompatibilities</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;0&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;3&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59 &#40;16&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">102 &#40;27&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">132 &#40;35&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50 &#40;13&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;2&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Cardiovascular risk factors &#40;CVRF&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>High blood pressure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">295 &#40;80&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypercholesterolaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">227 &#40;61&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Urine protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">161 &#40;43&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">127 &#40;34&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Obesity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">104 &#40;28&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypertriglyceridaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85 &#40;23&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">82 &#40;22&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Patients with &#8805;1 CVRF prior to transplant</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">331 &#40;90&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Good control according to objective parameters or confirmed&#58; PAS&#47;PAD<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>130&#47;80<span class="elsevierStyleHsp" style=""></span>mmHg&#59; urine protein 24<span class="elsevierStyleHsp" style=""></span>h &#8804;300<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&#59; hemoglobin<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Final visit &#40;month 6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">High blood pressure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Good control according to doctor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Good control according to objective parameters&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Urine protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Good control according to doctor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">82&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Good control according to objective parameters&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Good control according to doctor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Good control according to objective parameters&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">89&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Degree of control of risk factors of kidney dysfunction &#40;hypertension&#44; urine protein and anemia&#41; in the final visit&#46;</p>"
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      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:34 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic allograft nephropathy&#58; current concepts and future directions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "B&#46;J&#46; Nankivell"
                            1 => "J&#46;R&#46; Chapman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.tp.0000190423.82154.01"
                      "Revista" => array:6 [
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            1 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Strategies to improve long-term outcomes after renal transplantation"
                      "autores" => array:1 [
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                          "etal" => false
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                            0 => "M&#46; Pascual"
                            1 => "T&#46; Theruvath"
                            2 => "T&#46; Kawai"
                            3 => "N&#46; Tolkoff-Rubin"
                            4 => "A&#46;B&#46; Cosimi"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra011295"
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            2 => array:3 [
              "identificador" => "bib0180"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "The natural history of chronic allograft nephropathy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "B&#46;J&#46; Nankivell"
                            1 => "R&#46;J&#46; Borrows"
                            2 => "C&#46;L&#46; Fung"
                            3 => "P&#46;J&#46; O&#8217;Connell"
                            4 => "R&#46;D&#46; Allen"
                            5 => "J&#46;R&#46; Chapman"
                          ]
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa020009"
                      "Revista" => array:6 [
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            ]
            3 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic renal allograft dysfunction"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;R&#46; Chapman"
                            1 => "P&#46;J&#46; O&#8217;Connell"
                            2 => "B&#46;J&#46; Nankivell"
                          ]
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2005050463"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
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                        "volumen" => "16"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16120819"
                            "web" => "Medline"
                          ]
                        ]
                      ]
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            ]
            4 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The burden of chronic kidney disease in renal transplant recipients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "V&#46; Karthikeyan"
                            1 => "J&#46; Karpinski"
                            2 => "R&#46;C&#46; Nair"
                            3 => "G&#46; Knoll"
                          ]
                        ]
                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Transplant"
                        "fecha" => "2004"
                        "volumen" => "4"
                        "paginaInicial" => "262"
                        "paginaFinal" => "269"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14974949"
                            "web" => "Medline"
                          ]
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            5 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic kidney disease and the transplant recipient"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;S&#46; Gill"
                            1 => "B&#46;J&#46; Pereira"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood Purif"
                        "fecha" => "2003"
                        "volumen" => "21"
                        "paginaInicial" => "137"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12596760"
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                          ]
                        ]
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            ]
            6 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anemia in solid organ transplantation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Ma&#322;yszko"
                            1 => "B&#46; Watschinger"
                            2 => "P&#46; Przyby&#322;owski"
                            3 => "M&#46; Durlik"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Transplant"
                        "fecha" => "2012"
                        "volumen" => "17"
                        "paginaInicial" => "86"
                        "paginaFinal" => "100"
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Article information

ISSN: 20132514
Original language: English

DOI:10.1016/j.nefroe.2015.06.005

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Year/Month	Html	Pdf	Total

2024 November	4	5	9
2024 October	45	37	82
2024 September	55	24	79
2024 August	63	71	134
2024 July	36	18	54
2024 June	64	34	98
2024 May	56	29	85
2024 April	61	26	87
2024 March	52	19	71
2024 February	54	35	89
2024 January	32	21	53
2023 December	37	24	61
2023 November	33	24	57
2023 October	48	20	68
2023 September	37	27	64
2023 August	34	23	57
2023 July	37	18	55
2023 June	36	20	56
2023 May	41	32	73
2023 April	29	13	42
2023 March	59	17	76
2023 February	41	13	54
2023 January	33	35	68
2022 December	71	26	97
2022 November	53	20	73
2022 October	66	48	114
2022 September	41	23	64
2022 August	51	38	89
2022 July	31	45	76
2022 June	34	40	74
2022 May	28	33	61
2022 April	35	43	78
2022 March	50	39	89
2022 February	43	37	80
2022 January	37	26	63
2021 December	44	39	83
2021 November	30	39	69
2021 October	50	41	91
2021 September	54	29	83
2021 August	25	45	70
2021 July	73	30	103
2021 June	51	36	87
2021 May	37	29	66
2021 April	61	38	99
2021 March	36	33	69
2021 February	33	13	46
2021 January	36	11	47
2020 December	16	14	30
2020 November	35	16	51
2020 October	18	19	37
2020 September	30	12	42
2020 August	43	11	54
2020 July	40	13	53
2020 June	29	11	40
2020 May	37	12	49
2020 April	33	21	54
2020 March	30	11	41
2020 February	32	25	57
2020 January	49	26	75
2019 December	39	26	65
2019 November	37	21	58
2019 October	19	15	34
2019 September	30	17	47
2019 August	35	14	49
2019 July	39	22	61
2019 June	48	33	81
2019 May	26	20	46
2019 April	69	53	122
2019 March	29	23	52
2019 February	28	16	44
2019 January	32	24	56
2018 December	148	48	196
2018 November	417	16	433
2018 October	401	24	425
2018 September	186	13	199
2018 August	38	10	48
2018 July	26	9	35
2018 June	33	12	45
2018 May	33	17	50
2018 April	41	7	48
2018 March	45	4	49
2018 February	37	8	45
2018 January	41	9	50
2017 December	36	8	44
2017 November	50	11	61
2017 October	43	14	57
2017 September	41	9	50
2017 August	51	17	68
2017 July	48	6	54
2017 June	63	12	75
2017 May	46	7	53
2017 April	52	14	66
2017 March	46	27	73
2017 February	59	23	82
2017 January	40	22	62
2016 December	103	8	111
2016 November	153	18	171
2016 October	201	20	221
2016 September	234	4	238
2016 August	301	7	308
2016 July	261	7	268
2016 June	206	0	206
2016 May	188	0	188
2016 April	143	0	143
2016 March	146	0	146
2016 February	226	0	226
2016 January	179	0	179
2015 December	200	0	200
2015 November	200	0	200
2015 October	199	0	199
2015 September	159	0	159
2015 August	153	0	153
2015 July	41	0	41

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