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Background Post-transplant prediabetes (PreDM) and diabetes (PTDM) are common and have an impact on cardiovascular events. We sought to investigate the pathogenesis and best approach for prediction. Methods We prospectively studied 115 waitlisted patients from a single center without manifest diabetes. An oral glucose tolerance test (OGTT) was performed yearly until transplantation and 12 months later. Insulin secretion, insulin sensitivity (IS) and disposition index (DI) were derived from the OGTT. Results PreDM and PTDM were observed in 27% and 28.6% of patients, respectively. Pretransplant age, body mass index (BMI), 120 min glucose, IS, DI, and prediabetes or undiagnosed diabetes were significantly associated with these alterations. In multivariate analysis, pretransplant age [odds ratio (OR) 1.5; 95% confidence interval (CI) 1.04–2.1], BMI (OR 1.16; 95% CI 1.04–1.3) and cumulative steroids (OR 1.5; 95% CI 1.02–2.2) were predictors of PreDM or PTDM. Receiver operating characteristic curve analysis showed that pretransplant BMI and 120 min glucose had the highest area under the curve (0.72; 95% CI 0.62–0.8; and 0.69; 95% CI 0.59–0.79, respectively). The highest discrimination cut-off for BMI (≥28.5 kg/m2) and 120 min glucose (≥123.5 mg/dL) yielded a similar number needed to diagnose (2.5). Conclusions PreDM or PTDM develops in waitlisted patients with an ineffective insulin secretion and BMI shows a similar diagnostic capacity to OGTT. Pretransplant interventions may reduce post-transplant glucose alterations.

Background Post-transplant diabetes mellitus (PTDM) beyond 12 months (late PTDM) is a severe complication after renal transplantation. Late PTDM develops mostly in subjects with prediabetes. Although exercise may have a potential role in preventing late PTDM, there is no previous data on the effect of exercise in patients with prediabetes. Material and methods we designed a 12-month exploratory study to test the capacity of exercise in reverting prediabetes in order to prevent late-PTDM. The outcome was the reversibility of prediabetes, assessed every 3 months with an oral glucose tolerance test (OGTT). The protocol included an incremental plan of aerobic and/or strength training as well as an active plan for promoting adherence (telephone calls, digital technology, and visits). Results the study included 27 prediabetic patients and was early interrupted due to efficacy. At the end of follow-up, 16 (60%) patients reverted to normal glucose levels at fasting and at 120 min after the OGTTs, two time higher than the 25–30% reversibility rate shown in a previous publication, p value

Background In living kidney transplantation there are two different individuals, a healthy donor and a renal transplant recipient. This is an excellent human model to study factors that influence kidney function in the context of reduced renal mass and the adaptation of two comparable kidneys to different metabolic demands. Methods We analyzed the changes in measured glomerular filtration rate (GFR, iohexol) from pretransplantation to 12 months after transplantation in 30 donor–recipient pairs. Each donor was compared with his/her recipient. We defined a priori three different groups based on GFR differences at 12 months: donor > recipient (Group A; 78 ± 8 versus 57 ± 8 mL/min), donor Results In Group A donors were mostly male and recipients were female (75% each). Donors had a higher baseline weight than their recipients. During follow-up, weight remained stable in donors but increased 7% in recipients. In Group B donors were mostly female (60%) and recipients male. At baseline, donors had a lower weight than recipients. At 12 months, weight was stable in donors but increased in recipients. In Group C donors were mostly (75%) female and recipients male. At baseline, donors had a higher BMI than their recipients. At 12 months, BMI was stable in donors but increased 14% in recipients. In multivariable analysis, higher GFR at 12 months was associated with higher baseline weight and GFR in donors and with male gender and higher baseline weight in recipients. Conclusions Kidneys from living donors are more ‘plastic’ than originally thought and respond to metabolic demands and weight changes of their new host. These changes should be taken into account when assessing GFR outcomes in this population.

Background Diabetes is a risk factor for cancer in the general population. However, few data are available on the association between post-transplant diabetes mellitus (PTDM) and cancer after transplantation. Methods We analyzed this issue in a Spanish cohort of patients without diabetes before transplantation. PTDM was diagnosed with consensus criteria at 12 months after transplantation and 12 months before the diagnosis of cancer. The association between PTDM and cancer (overall and specific types) was evaluated with regression analysis. Results During a follow-up of 12 years (interquartile range 8–14), 85 cases of 603 developed cancer (829/100 000/year) and 164 (27%) PTDM. The most frequent cancers were renal cell cancer (RCC) n = 15, 146/cases/100 000/year), lung (n = 12, 117/cases/100 000/year), colon (n = 9, 88/cases/100 000/year) and prostate (n = 9, 88/cases/100 000/year). In logistic regression, PTDM was not associated with cancer. Eight of the 164 patients with PTDM (4.9%) vs 7 of the 439 without PTDM developed RCC (1.6%) (P = .027). In multivariate analysis, PTDM was independently associated with RCC [odds ratio (OR) 2.92, confidence interval (CI) 1.03–8.27], adjusting for smoking (OR 4.020, 95% CI 1.34–12.02) and other covariates. PTDM was not associated with other types of cancer. Conclusions Patients with PTDM must be considered a population at risk for RCC and accordingly, the subject of active surveillance.

Trasplante renal de donante vivo; Tratamiento de la enfermedad renal Living donor kidney transplantation; Chronic kidney disease treatment Trasplantament renal de donant viu; Tractament de la malaltia renal El trasplante renal de donante vivo (TRDV) es la opción terapéutica con las mejores expectativas de supervivencia para el injerto y para el paciente con insuficiencia renal terminal; sin embargo, este tipo de trasplantes ha experimentado un descenso progresivo en los últimos años en España. Entre las posibles explicaciones del descenso de actividad se encuentra la coincidencia en el tiempo con un aumento en el número de donantes renales fallecidos, tanto por muerte encefálica como por asistolia controlada, que podría haber generado una falsa impresión de ausencia de necesidad del TRDV. Además, la disponibilidad de un mayor número de riñones para trasplante habría supuesto un incremento en la carga de trabajo de los profesionales que pudiera enlentecer los procesos de donación en vida. Otro posible argumento radica en un posible cambio de actitud hacia posturas más conservadoras a la hora de informar a pacientes y a familiares acerca de esta opción terapéutica, a raíz de los artículos publicados respecto al riesgo de la donación a largo plazo. Sin embargo, existe una importantísima variabilidad en la actividad entre centros y comunidades autónomas, no explicada por el volumen de trasplante procedente de otros tipos de donante. Este dato, unido a que la indicación de donación renal en vida se realiza de manera mayoritaria en situación de enfermedad renal crónica avanzada (ERCA) y que el tiempo en diálisis es un factor pronóstico negativo respecto a la supervivencia postrasplante, permite concluir que el descenso depende además de otros factores. Por este motivo, en la reunión anual de equipos de trasplante renal, celebrada en la sede de la Organización Nacional de Trasplantes (ONT) en 2018, se constituyó un grupo de trabajo formado por equipos de trasplante renal, el grupo de trasplantes de la Sociedad Española de Nefrología (SEN) (SENTRA), la Sociedad Española de Trasplantes (SET) y la ONT, con el objetivo de identificar otras causas que condicionaron el descenso de la actividad de este tipo de trasplantes en España y su posible relación con la gestión del proceso de donación de vivo. El grupo de trabajo diseñó un cuestionario de autoevaluación, que fue cumplimentado por las 33 unidades de trasplante renal de donante vivo activas en España. El cuestionario contiene preguntas sobre las diferentes fases del proceso de donación de vivo: información inicial, estudio del donante vivo e información de los riesgos, consentimiento, recursos humanos (RRHH), nefrectomía, trasplante y seguimiento posterior. El análisis de las respuestas ha dado como resultado la creación de un análisis de debilidades, amenazas, fortalezas y oportunidades (DAFO) del programa a nivel nacional y ha permitido elaborar recomendaciones específicas dirigidas a mejorar cada una de las fases del proceso de donación en vida. El documento, denominado Análisis de situación del trasplante renal de donante vivo y hoja de ruta ha sido también revisado por un panel de expertos en TRDV, representantes de varias sociedades científicas implicadas (Asociación Española de Urología [AEU], Sociedad Española de Enfermería Nefrológica [SEDEN], Sociedad Española de Inmunología [SEI/GETH]), el Grupo de Trabajo Enfermedad Renal Crónica Avanzada (ACERCA), la Asociación de Pacientes para la Lucha Contra la Enfermedad Renal (ALCER) y sometido posteriormente a consulta pública. Tras incluir las mejoras sugeridas, el documento final ha sido adoptado institucionalmente en el Consejo Interterritorial de Trasplantes (CIT) del Sistema Nacional de Salud. El trabajo realizado y las recomendaciones para optimizar el TRVD se describen a lo largo del presente artículo, organizados por los diferentes apartados del proceso de donación. Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spain have adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.

Obesity is an established risk factor for renal disease and for disease progression. Therefore, an accurate determination of renal function is necessary in this population. Renal function is currently evaluated by estimated glomerular filtration rate (GFR) by formulas, a procedure with a proven high variability. Moreover, the adjustment of GFR by body surface area (BSA) confounds the evaluation of renal function. However, the error of using estimated GFR adjusted by BSA has not been properly evaluated in overweight and obese subjects. We evaluated the error of 56 creatinine- and/or cystatin-C-based equations and the adjustment of GFR by BSA in 944 subjects with overweight or obesity with or without chronic kidney disease (CKD). The error between estimated (eGFR) and measured GFR (mGFR) was evaluated with statistics of agreement: the total deviation index (TDI), the concordance correlation coefficient (CCC) and the coverage probability (cp). The error of eGFR by any equation was common and wide: TDI averaged 55%, meaning that 90% of estimations ranged from −55 to 55% of mGFR. CCC and cp averaged 0.8 and 26, respectively. This error was comparable between creatinine and cystatin-C-based formulas both in obese or overweight subjects. The error of eGFR was larger in formulas that included weight or height. The adjustment of mGFR or eGFR led to a relevant underestimation of renal function, reaching at least 10 mL/min in 25% of the cases. In overweight and obese patients, formulas failed in reflecting real renal function. In addition, the adjustment for BSA led to a relevant underestimation of GFR. Both errors may have important clinical consequences. Thus, whenever possible, the use of a gold standard method to measure renal function is recommended. Moreover, the sense of indexing for BSA should be re-considered and probably abandoned.

BackgroundReliable determination of glomerular filtration rate (GFR) is crucial in the evaluation of living kidney donors. Although some guidelines recommend the use of measured GFR (mGFR), many centres still rely on estimated GFR (eGFR) obtained through equations or 24-h creatinine clearance. However, eGFR is neither accurate nor precise in reflecting real renal function. We analysed the impact of eGFR errors on evaluation and decision making regarding potential donors.MethodsWe evaluated 103 consecutive living donors who underwent mGFR via iohexol plasma clearance and eGFR by 51 creatinine- and/or cystatin C–based equations. The cut-off for living donation in our centre is GFR > 80 mL/min for donors >35 years of age or 90 mL/min for those ResultsNinety-three subjects (90.3%) had mGFR values above (donors) and 10 [9.7% (95% confidence interval 5.4–17)] below (non-donors) the cut-off. In non-donors, most of the equations gave eGFR values above the cut-off, so donation would have been allowed based on eGFR. All non-donors were female with reduced weight, height and body surface. In donors, up to 32 cases showed eGFR below the cut-off, while mGFR was actually higher. Therefore an important number of donors would not have donated based on eGFR alone.ConclusionThe misclassification of donors around the cut-off for donation is very common with eGFR, making eGFR unreliable for the evaluation of living kidney donors. Whenever possible, mGFR should be implemented in this setting.

The evaluation of renal function changes over time is crucial in day-to-day renal transplant care, and the slope of renal function is a major outcome in clinical trials. Little is known about the reliability of estimated glomerular filtration rate (eGFR) in reflecting real glomerular filtration rate (GFR) changes.We analyzed the variability of eGFR slope by 63 equations in estimating measured GFR (mGFR) changes in 110 renal transplant patients. The agreement between eGFR and mGFR slopes was evaluated by the concordance correlation coefficient and the limits of agreement. Patients were grouped based on mGFR slope in rapid GFR loss: faster than -3 mL/min/y; stable renal function: -3 to +3 mL/min/y; and improvement in GFR: higher than +3 mL/min/y.Concordance correlation coefficient averaged 0.36 and limits of agreement ±10 mL/min/y, indicating very poor agreement between eGFR and mGFR slopes. The eGFR slope classified patients into the same group of mGFR slope only in 25% of the cases. In about two-thirds of patients, the eGFR slope was either markedly faster or slower than the mGFR slope. In half of these cases, the discrepancy between mGFR and eGFR slopes was ≥50%.Formulas are neither accurate nor precise in reflecting real GFR decline in renal transplant patients, making them unreliable for clinical practice and trials.

Background The use of mycophenolic acid (MPA) in women during pregnancy causes an increase in miscarriages and birth defects with a typical embryopathy profile. Although epidemiological data does not suggest a greater risk among the offspring of male kidney transplant recipients, the European Medicines Agency and The Spanish Agency of Medicines and Medical Devices introduced the recommendation of using contraceptive methods. Methods We conducted a national retrospective study in 15 Spanish Kidney Transplant Centers to evaluate the frequency of miscarriages and birth defects between the offspring from male kidney transplants recipients. We included 151 males who had fathered 239 offspring, 225 under MPA and 14 without MPA. Results The results of our study showed an incidence of miscarriages in the MPA group of 9.8%, and of birth defects of 4%. Conclusions We observed an incidence of miscarriages between the offspring fathered by kidney transplant males under MPA lower than the general population. The incidence of birth defects was similar to the incidence described in other studies and the fact that we did not find the typical embryopathy profile makes it difficult to associate them to the use of MPA. Because of that, we urge the European and Spanish Agencies to reconsider their recommendations for males.

Background and Aims Mycophenolic acid (MPA) is one of the most used immunosuppressive drugs. It is teratogenic in women with a typical embryopathy profile. Regarding its effect on the children of male kidney transplant recipients, although clinical evidence does not indicate a greater risk of malformations, the European Medicines Agency and the Spanish Agency for Medicines and Health Products introduced in 2015 the recommendation to use contraceptive methods because of their genotoxic potential. For this reason, we propose to study the results of the Spanish Kidney Transplant Centers. Method Multicenter retrospective observational study in which 15 Kidney Transplant Centers have participated. Of 3934 men ≤ 60 years old that received a kidney transplant between 2000 and 2015, 3023 were contacted, and 159 men who fathered at least one post-transplant pregnancy (total 252 fetuses) were included. We compared the incidence of abortions and live births with malformations among those who received MPA at the time of conception vs. those who did not. Results In the 252 fetuses (characteristics in table 1) there was an exitus and no differences were detected in the incidence of abortions between the group exposed to MPA (n = 230) and the unexposed group (n = 22), 11.3% vs 18.2%, p = 0.31. Among the 221 live-born fetuses, no differences were found in congenital malformations between the group exposed to MPA (n = 203) and the unexposed (n = 18) 4.9% vs. 16.7%, p = 0.07. Among the malformations described, the typical embryopathy profile of the MPA was not found. Conclusion According to the data of this retrospective national multicenter study, the use of MPA in male kidney transplant recipients does not cause a greater number of abortions or congenital malformations. For these reasons, and given the evidence also published by other groups, it seems necessary to reevaluate the recommendation given on contraception in men treated with MPA.

Background: Post-transplant diabetes mellitus (PTDM) is a frequent and severe complication after renal transplantation. In fact, PTDM is a risk factor for both infection and cardiovascular diseases. The prevalence and incidence of PTDM have a bimodal evolution: early (up to 3 months) and late PTDM (beyond 12 months). The majority of late PTDM occurs in subjects with prediabetes after transplantation. So, treating patients with prediabetes, a potentially reversible condition, might help preventing PTDM. In the general population, exercise prevents the evolution from prediabetes to diabetes. However, in renal transplantation, not enough evidence is available in this field. Objectives: We designed an exploratory analysis to evaluate the feasibility of exercise to reverse prediabetes as a first step in the design of a trial to prevent PTDM. Methods: Only patients with prediabetes beyond 12 months after transplantation with capacity to perform exercise will be included. Prediabetes will be diagnosed based on fasting glucose levels and oral glucose tolerance tests (OGTTs). Patients will be treated with a stepped training intervention, starting with aerobic exercise training (brisk walking, swimming, and cycling) 5 times per week and 30 min/day. Aerobic exercise training will be gradually increased to 60 min/day or eventually combined with anaerobic exercise training in case of persistent prediabetes. The reversibility/persistence of prediabetes will be measured with fasting glucose and OGTTs every 3 months. This study will last for 12 months.

Prediabetes and post-transplant diabetes mellitus affect about 20-30% of renal transplant patients. The latter is a risk factor for cardiovascular disease. However, no clear evidence linking prediabetes and cardiovascular disease is available. To study this we analyzed the impact of prediabetes on cardiovascular disease in 603 renal transplant patients followed with repeated oral glucose tests for up to five years and a long term survival evaluation. Prediabetes and post-transplant diabetes mellitus were defined at 12 months after transplantation to avoid their high reversibility rate before this period. 73 cardiovascular events were observed. The incidence of events was significantly higher in patients with either prediabetes, (17%; 0.023 person/year) or post-transplant diabetes mellitus (20%; 0.028 person/year) than in normal individuals, (7%; 0.0095 person/year). The incidence of events was comparable between prediabetes and post-transplant diabetes mellitus. Prediabetes at 12 months was a risk factor for cardiovascular events in univariate and multivariate Cox survival analyses (hazard ratio 2.24, 95% confidence interval 1.11-4.52). Prediabetes at three months and hemoglobin A1c at 12 months were not significantly associated with cardiovascular disease. Thus, prediabetes is a risk factor for cardiovascular disease in renal transplantation, a population at high risk for cardiovascular events. Since prediabetes is potentially a reversible condition, there is an opportunity to prevent cardiovascular disease in this population.

Type 2 diabetes mellitus represents 30&ndash, 50% of the cases of end stage renal disease worldwide. Thus, a correct evaluation of renal function in patients with diabetes is crucial to prevent or ameliorate diabetes-associated kidney disease. The reliability of formulas to estimate renal function is still unclear, in particular, those new equations based on cystatin-C or the combination of creatinine and cystatin-C. We aimed to assess the error of the available formulas to estimate glomerular filtration rate in diabetic patients. We evaluated the error of creatinine and/or cystatin-C based formulas in reflecting real renal function over a wide range of glomerular filtration rate (from advanced chronic kidney disease to hyperfiltration). The error of estimated glomerular filtration rate by any equation was common and wide averaging 30% of real renal function, and larger in patients with measured glomerular filtration rate below 60 mL/min. This led to chronic kidney disease stages misclassification in about 30% of the individuals and failed to detect 25% of the cases with hyperfiltration. Cystatin-C based formulas did not outperform creatinine based equations, and the reliability of more modern algorithms proved to be as poor as older equations. Formulas failed in reflecting renal function in type 2 diabetes mellitus. Caution is needed with the use of these formulas in patients with diabetes, a population at high risk for kidney disease. Whenever possible, the use of a gold standard method to measure renal function is recommended.

Background: Prediabetes and post-transplant diabetes mellitus (PTDM) affect about 20-30% of renal transplant patients. PTDM is a risk factor for cardiovascular disease. However, no clear evidence linking prediabetes and cardiovascular disease is available. Methods: We analyzed the impact of prediabetes on cardiovascular disease in 603 renal transplant patients followed with repeated OGTTs up to 5 years and a long term survival evaluation. Findings: Prediabetes and PTDM were defined at 12 months after transplantation to avoid their high reversibility rate before this period. 73 cardiovascular events were observed. The incidence of events was higher in patients with prediabetes, 28 (17%) or PTDM 20 (20%) than in normal subjects, 25 (7%), p = 0·001 and < 0·0001, respectively. The incidence of events was comparable between prediabetes and PTDM (p = 0·27). Prediabetes at 12 months was a risk factor for cardiovascular events in univariate and multivariate COX survival analyses (HR:2·24 95% CI 1·11-4·52). Prediabetes at 3 months and HbA1c at 12 months were not significant. Interpretation: Prediabetes was a risk factor for cardiovascular disease in renal transplantation, a population at high risk for cardiovascular events. Prediabetes is a potentially reversible condition, which offers the opportunity to prevent cardiovascular disease in this population. Funding Statement: Instituto de Salud Carlos III: The authors would like to acknowledge (a) the IMBRAIN project (FP7-RE6-POT-2012-CT2012- 31637-IMBRAIN) funded under the 7th Frameworks Programme (capacities), (b) the Instituto de Salud Carlos III (Fondo de Investigacioen Sanitaria: FIS) and Fondos FEDER for the following grants: PI 07/0732, the REDINREN RD/0021/0008 and PI10/02428 and (c) the funding of the Spanish Research Network for Kidney Diseases (REDINREN RD12/0021/0008). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of each hospital and followed the Declaration of Helsinki.

Background Formulas do not estimate renal function with acceptable precision and accuracy. Methods We compared 51 creatinine-based and/or cystatin c-based formulas with a gold standard (iohexol plasma clearance) in 193 renal transplant recipients using concordance correlation coefficient, total deviation index, coverage probability and the error in chronic kidney disease (CKD) stage classification. Results No formula showed a concordance correlation coefficient greater than 0.90 (average for creatinine-based formulas: ∼0.70 and for cystatin c-based formulas: ∼0.85). A wide total deviation index was observed: approximately 70% (creatinine-based) and approximately 50% (cystatin c-based), indicating that 90% of the estimations showed bounds of error of ±70% or ±50%, respectively, compared with the gold standard. No formula included 90% of the estimations within a coverage probability of ±10%. Half the CKD stages classified by creatinine-based formulas were incorrect, mainly due to overestimation of renal function. One of 3 CKD stages diagnosed by cystatin c-based formulas was incorrect, with both overestimation and underestimation. Overall, the formulas showed very low precision and accuracy and a high degree of error in reflecting real renal function. Conclusions In conclusion, formulas do not properly reflect renal function in kidney transplantation, which makes their use in clinical practice unreliable. Moreover, their use in clinical trials should be avoided.

Background Chronic kidney disease (CKD) affects 10-13% of the population worldwide. CKD classification stratifies patients in five stages of risk for progressive renal disease based on estimated glomerular filtration rate (eGFR) by formulas and albuminuria. However, the reliability of formulas to reflect real renal function is a matter of debate. The effect of the error of formulas in the CKD classification is unclear, particularly for cystatin C-based equations. Methods We evaluated the reliability of a large number of cystatin C and/or creatinine-based formulas in the definition of the stages of CKD in 882 subjects with different clinical situations over a wide range of glomerular filtration rates (GFRs) (4.2-173.7 mL/min). Results Misclassification was a constant for all 61 formulas evaluated and averaged 50% for creatinine-based and 35% for cystatin C-based equations. Most of the cases were misclassified as one stage higher or lower. However, in 10% of the subjects, one stage was skipped and patients were classified two stages above or below their real stage. No clinically relevant improvement was observed with cystatin C-based formulas compared with those based on creatinine. Conclusions The error in the classification of CKD stages by formulas was extremely common. Our study questions the reliability of both cystatin C and creatinine-based formulas to correctly classify CKD stages. Thus the correct classification of CKD stages based on estimated GFR is a matter of chance. This is a strong limitation in evaluating the severity of renal disease, the risk for progression and the evolution of renal dysfunction over time.

BACKGROUND The long-term clinical evolution of prediabetes and post-transplant diabetes mellitus (PTDM) is unknown. METHODS We analysed, in this cohort study, the reversibility, stability and progression of PTDM and prediabetes in 672 patients using repeated oral glucose tolerance tests (OGTTs) for ≤5 years. RESULTS Most patients were on tacrolimus, steroids and mycophenolate. About half developed either PTDM or prediabetes. The incidence of PTDM was 32% and bimodal: early PTDM (≤3 months) and late PTDM. Early PTDM reverted in 31%; late PTDM developed in patients with post-transplant prediabetes. The use of OGTTs was necessary to detect around half of PTDM. Pretransplant obesity was a major risk factor for early PTDM, for its persistence and for late PTDM {odds ratio [OR] 1.18 [95% confidence interval (CI) 1.09-1.28]}. At 3 months, higher HbA1c promoted [OR 2.37 (95% CI 1.38-4.06)], while insulin sensitivity protected against [OR 0.64 (95% CI 0.48-0.86)] late PTDM. At 3 months, 28% had prediabetes; of these, 36% remained stable, 43% normalized and 21% developed late PTDM. Pretransplant obesity [OR 1.20 (95% CI 1.04-1.39)] and higher HbA1c [OR 3.80 (95% CI 1.45-9.94)] at 3 months promoted while insulin sensitivity protected against [OR 0.57 (95% CI 0.34-0.95)] evolution from prediabetes to late PTDM. Immunosuppressive levels or acute rejection did not influence PTDM. Most (84%) of the patients with normal tests at 3 months remained stable without evolving into PTDM; 14% developed prediabetes. CONCLUSIONS PTDM and prediabetes are very common in renal transplantation. Classic metabolic factors like obesity, prediabetes and insulin resistance promote the evolution of PTDM and prediabetes. Patients with normal glucose metabolism rarely develop PTDM. OGTT is necessary to detect PTDM and prediabetes and thus should be included in clinical practice.

Lipid abnormalities may contribute to chronic allograft nephropathy (CAN). Apolipoprotein E (ApoE) gene polymorphism regulates lipoprotein metabolism, but little is known about an association between CAN and this polymorphism. The ApoE gene (E3/E4) polymorphism was typed by PCR assay (99 E3/E3, 28 E3/E4, 1 E4/E4) on 128 consecutive renal transplant patients with functioning grafts for more than 3 years (6.7 ± 2.8 years). Twenty-eight patients with histological CAN were compared with 100 patients who had no clinical evidence of chronic rejection (no proteinuria and sCr < 2.5 mg%). As expected, univariate analysis revealed that patients with CAN experienced a greater acute rejection rate (78% vs 21%; P = .001), a higher serum creatinine (3.6 ± 1.7 vs 1.4 ± 0.5 mg%; P = .0001), and an older organ donor (43 ± 20 vs 29 ± 13 years; P = .0001). The lipid profiles (total cholesterol and triglycerides levels) were similar in both groups with 60% in each group receiving anti-lipemic drugs. Interestingly, the ApoE epsilon 4 allele was overrepresented in the group with CAN (39% vs 17%, P = .019). Logistic regression analysis showed that the epsilon 4 allele was an independent predictor of CAN (OR: 3.4; CI 95%: 1.07 to 11; P = .040) as were donor age and acute rejection episodes. In conclusion, an interaction between risk factors and genetic factors may determine CAN in this population. This finding may help to target prophylactic interventions in these recipients.

Clinical impact of preexisting vascular calcifications on mortality after renal transplantation. Background Vascular calcifications (VC) are a well-known cardiovascular risk factor (CVRF) in uremic patients. However, their role on mortality after renal transplantation (RT) is unclear. Methods In 1117 RT recipients, we investigated the association between long-term survival and the presence of VC, evaluated by preoperative posteroanterior plain radiography from aorto-iliac region, at the time of RT. The primary study outcome was all-cause mortality. Other perioperative CVRF were also collected. Results VC were observed in 273 patients (24.4%) before RT; additionally, 132 (12%) patients died during follow-up, due, mainly, to cardiovascular (39%) or infectious (24%) complications. As expected, patients with VC showed a higher age and a greater number of CVRF than those without VC. Overall mortality rate was also higher in VC group (19 vs. 9.5%; P = 0.0001), as well as cardiovascular mortality (9.5 vs. 3.1; P = 0.048). Multivariate Cox model showed that VC were predictor of overall mortality [relative risk (RR) 1.8; 95% CI 1.1–2.8; P = 0.015] and cardiovascular mortality (RR 2.6; 95%CI 1.1–6); P = 0.033), independently of other CVRF. An interaction between the presence of VC and diabetes was found. The effect of VC on mortality was evident in nondiabetic patients, that is, those with VC had a significantly higher mortality rate than patients without VC (21 vs. 9%; P = 0.0001). By contrast, these differences were not observed in diabetic patients (16.5 vs. 14.3%; P = 0.656). Conclusion VC evaluated by a simple and inexpensive plain radiography are an independent predictor of cardiovascular and all-cause mortality following RT. This finding may encourage the implementation of appropriate therapeutic strategies after RT.

Background. Prognostic indices that estimate long-term mortality are essential not only to compare different clinical studies and populations but also to perform the most appropriate therapeutic interventions. All-cause mortality is high after renal transplantation (RTx), but no prognostic index has focused on predicting mortality in RTx. We developed and tested a prognostic index for mortality in RTx after hospitalization. Methods. We retrospectively analyzed survival in 1,293 RTx recipients who were randomly assigned to two groups: a modeling population (n=646), used to create the new index, and a testing population (n=647), used to test this index. Patients were stratified into three risk groups (low, medium, and high) by combining peritransplant risk factors for mortality (β-coefficient), using a simple eight-point check list: age, pretransplant cardiovascular disease, renal dysfunction at discharge, cardiac hypertrophy, vascular calcification, diabetes, time on dialysis, and acute tubular necrosis. Results. Overall lower survival rates were observed with increasing risk classes in the testing population (log-rank test=18; P=0.0001). The 8-year survival rates ranged from 94% in the lowest-risk group to 59% in the highest-risk group. The area under the receiver operating characteristic curve was 0.63. Mortality risk (Cox analysis) significantly increased with increasing risk classes (medium risk: relative risk=3.8, 95% confidence interval=1.5–9.5, P=0.004; high risk: relative risk=6.3, 95% confidence interval=2.4–16.2, P=0.0001). Conclusions. This simple prognostic index applicable at the bedside may accurately predict survival in RTx recipients after discharge. Consequently, targeted treatment interventions may be indicated for minimizing mortality, especially in high-risk groups.

Background and objectives: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. Method: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. Results: Vitamin D deficiency (250HD(3) = 2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100 pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. Conclusions: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients. Antecedentes y objetivos: La relación entre las alteraciones del metabolismo mineral, las fracturas óseas y las calcificaciones vasculares en receptores de un trasplante renal no han sido establecidas. Método: Realizamos un estudio transversal en 727 receptores estables procedentes de 28 centros de trasplante españoles. Se determinaron de manera centralizada los parámetros del metabolismo mineral; también se centralizó la semicuantificación de las fracturas vertebrales y de las calcificaciones de la aorta abdominal. Resultados: La deficiencia de vitamina D (25OHD3 < 15 ng/ml) fue más frecuente en mujeres y en los estadios CKD-T I-III (29, 6 vs. 44, 4%; p = 0, 003). La relación inversa y significativa observada entre los niveles de 25OHD3 y PTH fue modificada por el género de tal manera que la pendiente fue mayor en las mujeres que en los hombres (p = 0, 01). Un 15% de los receptores mostró alguna fractura vertebral (VFx) con un grado de deformidad =2. Los factores relacionados con la VFx diferían en función del género: en los hombres, la edad (OR: 1, 04; IC 95%: 1, 01-1, 06) y el tratamiento con CsA (OR: 3, 2; IC 95: 1, 6-6, 3); en las mujeres la edad (OR: 1, 07; IC 95%: 1, 03-1, 12) y los niveles de PTH (OR per 100 pg/ml increase: 1, 27; IC 95%: 1, 043-1, 542). Las calcificaciones de la aorta abdominal fueron comunes (67, 2%) y se relacionaron con los factores de riesgo clásicos, pero no con los parámetros del metabolismo mineral. Conclusiones: La deficiencia de vitamina D es más frecuente en las mujeres receptoras de un trasplante renal y en los estadios más tempranos de la CKD-T, y es un factor que contribuye al desarrollo de hiperparatiroidismo secundario. Las VFx prevalentes están relacionadas con unos niveles más elevados de PTH solamente en las mujeres.