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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.

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.

Antibody-mediated rejection (ABMR) is defined by specific histopathological lesions and evidence of circulating donor-specific antibodies (DSA). Although DSA are not always detectable, monitoring donor-reactive memory B cells (mBC) could identify patients at risk of developing ABMR. Peripheral donor-reactive mBC using a novel HLA B cell ELISpot assay, serum DSA, and numbers of different B cell subsets were assessed in 175 consecutive kidney transplants undergoing either for-cause or 6- and 24-month surveillance biopsies for their association with main histological lesions of ABMR and impact on allograft outcome. In 85 incident for-cause biopsies, high frequencies of donor-reactive mBC were detected in all 16 (100%) acute ABMR/DSA+ and most chronic ABMR, with or without DSA (24/30[80%] and 21/29[72.4%], respectively). In a longitudinal cohort of 90 nonsensitized patients, a progressively higher expansion of donor-reactive mBC than de novo DSA was observed at 6 and 24 months (8.8% vs 7.7% and 15.5% vs 11.1%, respectively) and accurately identified patients with ongoing subclinical ABMR (area under the curve = 0.917 and area under the curve = 0.809, respectively). An unsupervised hierarchical cluster analysis revealed a strong association between donor-reactive mBC with main fundamental allograft lesions associated with ABMR and conferred a significant deleterious impact on graft outcome. Monitoring donor-reactive mBC may be useful to further characterize humoral rejection after kidney transplantation.

Whether cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) at prophylaxis cessation predicts D+/R+ kidney transplants at risk of late-onset CMV infection after receiving distinct induction therapies is still not well characterized.We prospectively assessed CMV-specific CMI predicting late-onset CMV infection at prophylaxis withdrawal and at earlier time-points, in 96 consecutive D+/R+ patients receiving either anti-interleukin 2-receptor antibody (anti-IL2RA; n = 50) or rabbit antithymoglobulin (n = 46). CMV-specific CMI was evaluated against CMV antigens (IE-1, pp65) using an IFN-γ ELISpot assay.Fourteen (14.6%) of 96 patients developed late-onset CMV infection and 2 (2.1%) of 96 displayed disease. At 3 months, CMV-specific CMI frequencies were significantly lower in patients developing late-onset CMV infection (P0.001 for IE-1, P = 0.030 for pp65), regardless the type of induction therapy. Receiver operating characteristic curve analyses showed accurate CMV-specific CMI cutoffs (25 and 130 IFN-γ spots for IE-1 and pp65, respectively) classifying patients into high risk, intermediate risk, or low risk (log-rank = 0.006; hazard ratio, 4.084; 95% confidence interval, 1.431-11.651; P = 0.009), being IE-1 CMI the strongest predictor (odds ratio, 5.554; 95% confidence interval, 1.486-20.766; P = 0.011). Although the profound posttransplant CMV-specific CMI inhibition among rabbit antithymocyte globulin-treated patients precludes its use for risk stratification both before and early after kidney transplant, a similar proportion of at-risk patients could be identified before month 3 within anti-interleukin 2-receptor antibody-treated patients.Monitoring CMV-specific CMI at 3-month prophylaxis cessation discriminates kidney transplant recipient at risk of late-onset CMV infection, regardless the type of induction therapy.

Background Improving cytomegalovirus (CMV) immune-risk stratification in kidney transplantation is highly needed to establish guided preventive strategies. Methods This prospective, interventional, multicenter clinical trial assessed the value of monitoring pretransplant CMV-specific cell-mediated immunity (CMI) using an interferon-γ release assay to predict CMV infection in kidney transplantation. One hundred sixty donor/recipient CMV-seropositive (D+/R+) patients, stratified by their baseline CMV (immediate-early protein 1)–specific CMI risk, were randomized to receive either preemptive or 3-month antiviral prophylaxis. Also, 15-day posttransplant CMI risk stratification and CMI specific to the 65 kDa phosphoprotein (pp65) CMV antigen were investigated. Immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids in 80% of patients, whereas 20% received thymoglobulin induction therapy. Results Patients at high risk for CMV based on pretransplant CMI developed significantly higher CMV infection rates than those deemed to be at low risk with both preemptive (73.3% vs 44.4%; odds ratio [OR], 3.44 [95% confidence interval {CI}, 1.30–9.08]) and prophylaxis (33.3% vs 4.1%; OR, 11.75 [95% CI, 2.31–59.71]) approaches. The predictive capacity for CMV-specific CMI was only found in basiliximab-treated patients for both preemptive and prophylaxis therapy. Fifteen-day CMI risk stratification better predicted CMV infection (81.3% vs 9.1%; OR, 43.33 [95% CI, 7.89–237.96]). Conclusions Pretransplant CMV-specific CMI identifies D+/R+ kidney recipients at high risk of developing CMV infection if not receiving T-cell–depleting antibodies. Monitoring CMV-specific CMI soon after transplantation further defines the CMV infection prediction risk. Monitoring CMV-specific CMI may guide decision making regarding the type of CMV preventive strategy in kidney transplantation. Clinical Trials Registration NCT02550639.

Introduction: Despite the different assays available for immune-risk stratification before living-donor kidney transplantation (LDKT), the precise type and number of tests to perform remain uncertain. Methods: In a cohort of 330 consecutive LDKT patients, all of which were complement-dependent cytotoxicity (CDC)−crossmatch negative, we retrospectively analyzed the impact on main clinical outcomes of most sensitive immunoassays (complement-dependent cytotoxicity−panel-reactive antibody [CDC-PRA], flow cytometry crossmatch [FC-XM], donor-specific antibodies [DSAs], and their complement-binding capacity DSA-C3d]), together with donor/recipient HLA eplet matching. Mean follow-up was 67 months (range 24−190 months). Results: Of 330 patients, 35 (11%) showed a CDC-PRA >20%; 17 (5%) FC-XM+; 30 (9%) DSA+, 18(5%) DSA-C3d+, with low overlapping results (10 patients positive in all donor-specific tests). Unlike HLA allele compatibility, the mean number of HLA class II eplet mismatches was higher in LDKT patients with positive baseline test results. DSA-C3d+ showed higher mean fluorescence intensity (MFI) DSA, with a cut-off MFI of 6192 accurately predicting complement fixation (area under the curve = 0.85, P = 0.008). Although all assays were associated with acute rejection (AR), only DSA-C3d+ (odds ratio [OR] = 6.64, P = 0.038) or high MFI-DSA (OR = 7.54, P = 0.038) independently predicted AR. Likewise, poorly HLA class II eplet−matched patients were at higher risk for AR, particularly patients with negative baseline test results (OR = 1.14, P = 0.019). Finally, previous AR and FC-XM+/DSA+, regardless of C3d positivity, independently predicted graft loss. Conclusion: Combining FC-XM and solid-phase assays with the evaluation of donor/recipient HLA eplet mismatches, are most accurate tools for immune-risk stratification prior LDKT. Keywords: acute rejection, crossmatch immunoassays, donor-specific antibodies, HLA matchmaker, immune risk stratification, living donor kidney transplantation

Tacrolimus (Tac) has a narrow therapeutic window and shows large between-patient pharmacokinetic variability. As a result, over-immunosuppression and under-immunosuppression are frequently encountered in daily clinical practice. Unraveling the impact of genetic polymorphisms on Tac pharmacokinetics may help to refine therapy. In this study, the associations of single-nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes (CYP3A) with Tac pharmacokinetics were investigated in renal transplant recipients.In a cohort of 272 kidney transplant recipients, associations between functional genetic variants (CYP3A4*22 and CYP3A5*3) and dose-adjusted predose Tac concentrations (C0) and daily doses of Tac at days 5-7 and 15 and 1, 3, 6 and 12 months after renal transplantation were evaluated. Patients were genotyped and clustered according to both CYP3A4*22 and CYP3A5*3 allelic status: poor (PM) (CYP3A4*22 carriers with CYP3A5*3/*3), intermediate (IM) (CYP3A4*1/*1 with CYP3A5*3/*3 or CYP3A4*22 carriers with CYP3A5*1 carriers) and extensive CYP3A-metabolizers (EM) (CYP3A4*1/*1 and CYP3A5*1 carriers).EM had an 88% lower dose-adjusted C0 compared with IM. PM had a 26% higher dose-adjusted C0 compared with IM. The percentage of patients with supratherapeutic Tac exposure (C015 ng/ml) was significantly higher in PM (43.5%) compared with EM (0%) at days 5-7 after transplantation (P=0.01). About 30% of EM had subtherapeutic exposure (C05 ng/ml) at days 5-7 after transplantation (P=0.001).The combined CYP3A4 and CYP3A5 genotype of renal transplant recipients has a major influence on the Tac dose required to reach the target exposure.

Summary Background More than 30 face transplantations have been done worldwide since 2005 but no documented long-term follow-up has been reported in the literature. We aimed to answer remaining question about the long-term risks and benefits of face transplant. Methods In this single-centre, prospective, open study, we assessed 20 patients presenting with facial defects. Ten patients were selected, and, after three were secondarily excluded, seven were transplanted: two with neurofibromatosis 1, one with a burn, and four with self-inflicted facial gunshot injuries. We report the long-term outcomes of six face allotransplant recipients at an average of 6 years (range 3·4–9 years) after the transplantation. All admissions to hospital except for planned revisions and immunosuppressive follow-up therapy were reported as adverse events (safety endpoint). Predefined immunological, metabolic, surgical, and social integration endpoints were collected prospectively. Patients underwent quantitative health-related quality of life assessments through Short Form 36 health questionnaires. This study was registered with ClinicalTrials.gov, number NCT00527280. Findings Two of seven patients died: one at 65 days due to transplant destruction with concomitant pseudomonas infection and the second at 3·4 years after transplantation by suicide. The six patients alive at long-term follow-up presented with functional transplants. Safety endpoints were related to infection in the first month, acute rejection from 1 day to 7 years after transplantation, or side-effects of immunosuppressive therapy. Recurrent rejection episodes justified maintenance therapy with high-dose steroids at high levels in all patients at last follow-up, yet none of the patients developed diabetes. Three patients were found to have hypertension with one requiring therapy. All patients had a noticeable reduction in glomerular filtration rate. All recipients and their families accepted their transplant. Improvements in social integration and quality of life were highly variable among the patients and depended on baseline levels and psychiatric comorbidities. Interpretation These long-term results show the crucial effect of patients' social support and pre-existing psychiatric conditions on the risk–benefit ratio of facial transplantation. Careful preoperative patient selection and long-term postoperative follow-up programmes under strict institutional review board controls should be used for any future grafts of this type. Funding Protocole Hospitalier de Recherche Clinique (PHRC) National.

Cytomegalovirus (CMV) infection is still a major complication after kidney transplantation. Although cytotoxic CMV-specific T cells play a crucial role controlling CMV survival and replication, current pretransplant risk assessment for CMV infection is only based on donor/recipient (IgG)-serostatus. Here, we evaluated the usefulness of monitoring pre- and 6-month CMV-specific T cell responses against two dominant CMV antigens (IE-1 and pp65) and a CMV lysate, using an IFN-γ Elispot, for predicting the advent of CMV infection in two cohorts of 137 kidney transplant recipients either receiving routine prophylaxis (n = 39) or preemptive treatment (n = 98). Incidence of CMV antigenemia/disease within the prophylaxis and preemptive group was 28%/20% and 22%/12%, respectively. Patients developing CMV infection showed significantly lower anti-IE-1-specific T cell responses than those that did not in both groups (p0.05). In a ROC curve analysis, low pretransplant anti-IE-1-specific T cell responses predicted the risk of both primary and late-onset CMV infection with high sensitivity and specificity (AUC0.70). Furthermore, when using most sensitive and specific Elispot cut-off values, a higher than 80% and 90% sensitivity and negative predictive value was obtained, respectively. Monitoring IE-1-specific T cell responses before transplantation may be useful for predicting posttransplant risk of CMV infection, thus potentially guiding decision-making regarding CMV preventive treatment.

The survival after renal transplantation of patients with antineutrophil cytoplasmic antibody (ANCA)-associated to systemic vasculitis is as good as in other diseases, although most of the reports are based on small numbers of patients. Furthermore, it is not known whether comorbidities (cardiovascular [CV] disease and cancer) are more frequent than in general population. We report our experience and the analysis of the published data on this topic. The outcome after transplantation in 49 patients with ANCA-associated small vessel vasculitis was compared with a control group. The relapse rate of vasculitis was 0.01 per patient per year. Comparison with the control patients revealed no difference in long-term outcome, CV mortality or incidence of malignancies. In the published literature, patients with ANCA at transplantation and with Wegener's granulomatosis are at greater risk of relapse. Taking our own results together with the review of the literature, we conclude that patient and graft survival rates compare favorably with those in control group that the recurrence rate is very low and that there is no increase in the incidence of cancer or in CV mortality. Patients with ANCA at transplantation and with Wegener's granulomatosis have a higher relapse rate.

In our old-for-old program, we discard or allocate older extended criteria donor kidneys to single (SKT) or dual kidney transplantation (DKT) depending on histological Remuzzi's score in recipients older than 60 years. Here, we analyze the long-term results of this program and try to identify independent predictors of patient and graft survival. Between December 1996 and January 2008, we performed 115 SKT and 88 DKT. Discard rate was 15%. Acute rejection incidence was higher in SKT than in DKT (22.6% vs. 11.4%, p = 0.04). Renal function was better in DKT than in SKT up to 5 years after transplantation. Surgical complications were frequent in DKT. Ten-year cumulative graft survival was significantly lower in the SKT group (31% vs. 53%, p = 0.03). In SKT, histological score 4 provided similar graft survival than 3 or less, whereas in DKT score 4, 5 or 6 displayed similar outcome. Finally, independent predictors of graft survival were history of major adverse cardiac event and 1-year serum creatinine, rather than SKT or DKT. In conclusion, this biopsy-guided old-for-old strategy resulted in acceptable long-term graft survival. Our results suggest that DKT should be considered for scores of 5 or 6 only.

Cytomegalovirus (CMV) infection remains a major problem in renal transplant recipients. CMV produces not only febrile syndromes and/or visceral disease but also contributes to the development of acute rejection and chronic graft failure. Valganciclovir prophylaxis has represented a major advance in controlling this infection, but late CMV infection after prophylaxis can occur, especially when universal prophylaxis is used. The use of valganciclovir prophylaxis for 200 days is more effective than prophylaxis for 100 days but does not completely prevent this problem. Prophylaxis based on the detection of CMV viremia (early prophylaxis or preemptive therapy) may prevent the development of delayed CMV disease, but has the disadvantage of requiring more intensive monitoring of viremia and does not prevent the development of viremia and its potential consequences in the long term. This article reviews current recommendations for prophylaxis of CMV disease in renal transplantation.

The advent of novel immunosuppressive strategies in renal transplantation, with immunomodulatory properties, might facilitate long-term allograft survival. T-cell depletion, costimulation-blockade and mTor inhibition have been shown to favour anti-donor hyporesponsiveness. Recently, the combination of rATG, belatacept (Bela) and sirolimus (SRL) has been used in kidney transplantation, showing very low incidence of acute rejection and excellent 12-month graft and patient survival. Herein, we have analysed the 1-year evolution of memory/effector and regulatory T cells and assessed the donor-specific T-cell alloimmune response in a group of these patients and compared with others treated with a calcineurin-inhibitor(CNI)-based (rATG/tacrolimus/MMF), and two other Bela-based regimens (rATG/Bela/MMF and basiliximab/Bela/MMF/steroids). During the first year after transplantation, patients receiving rATG/Bela/SRL had significantly higher percentage of Tregs upon the memory T-cell compartment and showed a potent anti-donor suppressive activity. In an in vitro naive and memory/effector T-cell co-culture, the combination of costimulation-blockade and SRL could abrogate both antigen-specific T-cell responses as efficiently as using a CNI drug. The combination of T-cell depletion, costimulation-blockade and mTor inhibition seems to be able to allow Treg survival and inhibit donor-specific alloreactive effector immune responses after kidney transplantation in humans.

Background. The presence of a few circulating donor cells in recipient's blood was first thought to be only an epiphenomenon of solid organ transplantation, also called microchimerism, but several authors have suggested that these circulating cells may contribute to tolerance induction. This study aims to assess the rate of microchimerism after kidney transplantation and determine its influence on acute rejection in a 4-year follow-up. Methods. A total of 84 single-kidney recipients were included for microchimerism detection and quantification 2, 6, 12, and 18 months after transplantation by specific detection of non-shared STR, VNTR, human leukocyte antigen-A, -B, -DRB1, and SRY alleles. Kinetic establishment of microchimerism was monitored in a double kidney transplanted recipient for 150 min after declamping and after 7 days. Results. Microchimerism was detected in 56.2% of kidney recipients 2 months after transplantation (M2): this fell to 30.1% at 12 months. In renal calcineurin inhibitor-based immunosuppression cohort (n=73), the microchimerism-negative group (n=32) showed 37.9% biopsy-proven acute rejection (BPAR), whereas in the microchimerism-positive group (n=41), no recipient did (P

Introduction. Epidemiological studies have shown that demographic, clinical, and histological donor characteristics influence renal function after transplantation, but whether these variables are independent predictors has not been established. The aim of this study was to evaluate the relative contribution of different donor variables on glomerular filtration rates (GFRs) at 3 months. Patients and methods. We analyzed single renal transplants performed at our center from January 2000 to July 2004. Donor variables included age, gender, weight and height, cause of death, duration of brain death, serum creatinine at admission and preprocurement, history of arterial hypertension or diabetes mellitus, and smoking habit. Donor chronic damage score was calculated in preimplantation biopsies as was the addition of interstitial fibrosis, fibrous intimal thickening, and glomerulosclerosis ( 10% = 1). Donor and recipient GFRs were calculated according to the Cockroft-Gault formula. Results. We analyzed 202 transplants obtained from 113 deceased donors. A renal biopsy was available in 111 transplants. Recipient GFR at 3 months correlated negatively with donor age (R = -0.32, P

Cytomegalovirus (CMV) infection remains an important complication of transplantation. The last decade has been characterized by improvements to management that has reduced its morbidity and mortality. The advance has been particularly important in the diagnosis and prevention. Several techniques have been developed that allow the increasingly rapid and sensitive diagnosis. The different preventive strategies include use of appropriate blood products, immune globulin, and antiviral agents either as prophylaxis or pre-emptive therapy. The development of effective oral drugs as valganciclovir also represents a new advance. It is necessary to summarize these advances to facilitate the development of local policies reflecting recent changes. The Group of Study of Infections in Transplantation (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has therefore produced actual recommendations in the management of CMV infection after transplantation.

OBJECTIVES: Interferon-α (IFN) may have undesirable effects on a functioning graft. The aim of this study was to evaluate IFN treatment in kidney transplant candidates during the hemodialysis period as well as the results after transplantation. METHODS: A total of 29 noncirrhotic hemodialysis patients with chronic hepatitis C virus (HCV) infection (based on long-term rise in ALT, HCV serology, HCV RNA by polymerase chain reaction methods, and histological evidence) were included. Tolerability to IFN treatment, pre- and posttransplantation therapeutic results, and long-term outcome were recorded. IFN regimen consisted of 3 million units (MU) times per week after hemodialysis sessions for 6 months, followed by 1.5 MU after each hemodialysis session for an additional 6 months. All patients gave informed consent for participation. RESULTS: IFN therapy was fairly well tolerated. Adverse effects due to IFN toxicity, renal disease, or causes related to the immunological properties of IFN were observed in 24% of patients. At the end of treatment, ALT had normalized in 23/28 patients (82.1%), and HCV RNA had cleared in 23/28 patients (82.1%). During follow-up, HCV RNA was persistently negative in 18 patients (64%, including transplant recipients). A total of 14 patients (nine HCV RNA–negative) received a kidney transplant. Mean follow-up after the procedure was 41 ± 28 months. In all, 12 patients had a functioning graft, one had acute vascular rejection, and one died of carcinoma. All transplanted patients maintained normal ALT levels, and eight remained HCV RNA–negative. CONCLUSIONS: Treatment results in our study population were better than those observed in the general population. The long-term response achieved, which was maintained after transplantation, supports the use of IFN for HCV hepatitis in kidney transplant candidates under hemodialysis.

BACKGROUND The minimum sample size to perform a clinical trial aimed to modify the natural history of chronic allograft nephropathy (CAN) is very large. Since the presence of chronic tubulointerstitial damage in renal protocol biopsy specimens is an independent predictor of late outcome, we evaluated whether protocol biopsies could facilitate the design of trials aimed to prevent or treat CAN. METHODS Two hundred eighty-two protocol biopsy specimens were obtained 3 months after transplantation in 280 patients with serum creatinine levels

Fundamento Se presenta la experiencia del programa de trasplante hepatico del Hospital de Bellvitge en 500 trasplantes realizados durante 15 anos, con el objetivo de poner de manifiesto los cambios que se han producido y exponer los resultados a largo plazo de esta terapeutica. Pacientes y metodo Se consideraron y compararon 5 grupos de 100 trasplantes consecutivos (I-V). Resultados Las indicaciones mas frecuentes fueron el hepatocarcinoma (23%), la cirrosis alcoholica (22,8%) y la hepatopatia cronica por virus C (18,8%). En 59 pacientes se llevaron a cabo 65 retrasplantes (13%), cuyas indicaciones mas frecuentes fueron la trombosis arterial (13 pacientes) y el fallo primario del injerto (10 pacientes). En 19 enfermos se realizo un trasplante combinado hepatorrenal. La causa mas frecuente de muerte del donante en el grupo I fueron los traumatismos craneales (80%), mientras que en el grupo V fue la enfermedad vascular (52%). Otras diferencias significativas entre estos grupos se observan en la proporcion de pacientes en estadio 2 y 3 de la clasificacion UNOS (el 45 frente al 19%), en el consumo de hemoderivados (29,6 [26] frente a 4,6 [5,3] concentrados de hematies), en la frecuencia de reintervenciones por hemoperitoneo (el 22 frente al 5%), en la estancia en UCI (13 [13] frente a 7,4 [11] dias) y en el hospital 40 [52] frente a 23,7 [17] dias), y en la incidencia de rechazo (el 46 frente al 20%) y de fallo primario del injerto (el 9 frente al 3%). Sin embargo, la prevalencia de infeccion (el 48 frente al 54,5%) y la incidencia de complicaciones biliares (el 26 frente al 20%) no han presentado variaciones significativas. La supervivencia actuarial de los pacientes trasplantados desde 1990 es del 83 y del 70% al ano y a los 5 anos, respectivamente. Conclusiones Se observa una mejoria notable y progresiva de los resultados del trasplante hepatico. Sin embargo, los tumores de novo, la recidiva de la hepatitis por virus C y el rechazo cronico pueden limitar los resultados a largo plazo.

Fluvastatin and low-density lipoprotein oxidation in hypercholesterolemic renal transplant patients. Background Hyperlipidemia contributes to the development and progression of vascular disease in organ transplant patients. Oxidative modification of low-density lipoproteins (LDLs) has been suggested as a key event in early atherogenesis. Methods We conducted a pilot study in renal transplanted patients with persistent hypercholesterolemia above 6.5 mmol/liter. We studied the LDL oxidation before and after one year of fluvastatin treatment. Twenty patients (12 males and 8 females, 46 ± 10 years old) who received a kidney transplant 24 ± 18 months before the study were treated with fluvastatin (20 mg/day for 12 weeks). Patients with a total cholesterol under 6.3 mmol/liter continued to receive 20 mg/day for another 40 weeks (group I, N = 10). Nine patients with a total cholesterol above 6.3 mmol/liter received 40 mg/day for a further 40 weeks (group II). Results Cyclosporine levels did not experience a significant variation. Total and LDL cholesterol decreased significantly in both groups (21.7 and 27.9% in group I, 18.3 and 27.2% in group II, respectively). The lag-phase time, which was significantly enlarged before fluvastatin treatment in the patients with respect to the controls ( N = 18, 82 ± 45 vs. 50 ± 8 min) was shortened after one year of fluvastatin treatment (64 ± 24 vs. 50 ± 8 min, P = 0.04). Fluvastatin was stopped in only one patient because of nausea and vomiting. Transaminases and creatin-phospho-kinase were not altered. All of the patients maintained a functioning graft during the study period. Conclusions Fluvastatin significantly reduced total and LDL cholesterol, without interferences with cyclosporine A through levels. Fluvastatin has not demonstrated an antioxidant effect in our renal hypercholesterolemic transplant patients.

Background. Cyclosporine (CsA) nephrotoxicity can be identified by functional changes and chronic renal damage. CsA-associated renal fibrosis has been related to the overproduction of transforming growth factor (TGF)-β 1 , a fibrogenic cytokine. Mycophenolate mofetil (MMF) may allow CsA dose reduction without increasing the risk of rejection. Methods. We studied the impact of CsA dose reduction in association with MMF on renal function and TGF-β 1 production in 16 long-term renal allograft recipients with suspected CsA nephrotoxicity. Two grams/day of MMF were introduced, and CsA dose was reduced to reach whole-blood levels between 40 and 60 ng/ml within 1 month. CsA dose and levels, renal function parameters, and platelet-poor plasma TGF-β 1 levels were evaluated before and 6 months thereafter. Results. MMF allowed a decrease in both the mean dose of CsA (3.8±1.35 vs. 2.2±0.73 mg/kg/day; P

Introduction. Renal function predicts graft survival in kidney transplant patients. This study compared the 2-year evolution of renal function in patients treated with cyclosporine or tacrolimus in combination with mycophenolate mofetil (MMF) and prednisone. Methods. We studied 1558 cadaveric renal transplant recipients from 14 Spanish hospitals between January 2000 and December 2002. Of these, 1168 were treated with tacrolimus and 390 with cyclosporine. The primary efficacy endpoint was long-term renal function. Renal function was measured by serum creatinine and glomerular filtration rate (GFR) by creatinine clearance calculated from the Cockcroft-Gault formula. This report summarizes the 2-year results. Results. At 24 months the tacrolimus group showed significantly better serum creatinine (1.5 ± 0.7 vs 1.8 ± 0.8 mg/dL, P

Background. The aim of the present study was to analyze whether minor differences in recipient body surface area have any predictive value on renal allograft evolution. Methods. For this study, we considered 236 pairs of recipients who received a kidney from the same donor at our center between March 1985 and December 1995. Pairs in whom at least one patient presented any of the following events were excluded: graft loss during the first year of follow-up, diabetes mellitus, noncompliance with treatment, chronic pyelonephritis, and recurrent or de novo glomerulonephritis. Recipients of each pair were classified as large or small according to their body surface area (BSA). The percentage difference of BSA in each pair was calculated, and two cohorts of pairs were defined: BSA difference ≤10% (n=76 pairs) and BSA difference >10% (n=70 pairs). Results. The large recipients of the cohort with a BSA difference >10% showed a higher incidence of posttransplant delayed graft function (22/70 vs. 12/70, P=0.075), hypertension at 1 year of follow-up(51/70 vs. 35/70, P=0.006), and a higher serum creatinine level at 1-year follow-up (173 vs. 142 μmol/L,P=0.003), whereas in the cohort with a BSA difference≤10%, posttransplant evolution in large and small recipients was not different. Multivariate analysis showed that recipient BSA was an independent predictor of delayed graft function, posttransplant hypertension, and serum creatinine at 1-year follow-up. Conclusions. Relatively small differences in recipient BSA influence renal allograft evolution. Consequently, our data support that recipient size should be taken into consideration for renal allograft allocation.

The purpose of this study was to investigate the incidence and risk factors for the development of diabetes mellitus after kidney transplantation (PTDM). A total of 1783 nondiabetic renal allograft recipients transplanted from January 2000 to December 2002 were included. Diabetes was diagnosed following American Diabetes Association criteria. While 1276 patients were treated with tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids, 507 patients received cyclosporine-ME (CsA), MMF, and steroids. PTDM incidence at 6, 12, and 24 months was 14.2%, 12.8%, and 13.3%, respectively. Cumulative incidence during the follow-up was 21.6%. Only 121 of the diabetic patients (47.6%) at 6 months remained diabetic at 24 months. Furthermore, 60 patients of 116 patients on insulin at 6 months (51.7%) remained on treatment at 24 months. The cumulative incidence of PTDM was similar in the two immunosuppressive treatments (19.7% on CsA-MMF vs 22.3% on Tac-MMF; P = NS). However, at 24 months, 14 of 50 diabetic patients on CsA-MMF (28%) and 74 of 161 patients on Tac-MMF (45.9%) were on insulin treatment (P.05). By Cox regression analysis, age older than 60 years (RR 1.61; 95%CI 1.28-2.04; P.001), body mass index (BMI)30 kg/m2 at transplantation (RR 1.66; 95%CI 1.27-2.16; P.001), and immunosuppression with Tac (RR 1.30; 95%CI 1.02-1-66; P = .033) were associated with PTDM. In conclusions, the incidence of PTDM at 24 months in immunosuppressive protocols including MMF is about 22%, and it is associated with older age, increased BMI, and immnunosuppression with Tac.

Introduction. Calcineurin inhibitors may be associated with decreased arterial elasticity and increased vascular risk. We measured pulse wave velocity (PWV) in large or small arteries as an index of elasticity. The aim of our study was to determine aortic and radial arterial elasticity in 30 stable kidney transplant patients treated with calcineurin inhibitor immunosuppression. Patients and methods. In stable kidney transplant patients we determined the usual biochemical parameters as well as lipid profiles, 24-hour blood pressure (BP) monitoring (CBPM) using a chronobiological program (Garapa), and PWV with a HDI-PWV CR-2000 monitor. Results. Sixteen patients received cyclosporine (CsA, G-1) and 14 tacrolimus (G-2) immunosuppression. There were no baseline differences regarding age (G-1: 56 ± 12 years, G-2: 56 ± 14 years), renal transplant follow-up (G-1: 7 ± 3 years, G-2: 7.5 ± 3 years), Systolic BP, pulse pressure or plasma creatinine (G-1: 163 ± 35 umol/L, G-2: 173 ± 26 umol/L). Patients in the G-1 showed higher diastolic BP (79 ± 11 vs 74 ± 8 mm Hg), greater proteinuria (1.26 ± 0.4 vs 0.6 ± 0.2 g/d, P

Objective Our aim was to evaluate the efficacy and safety of adding adefovir to lamivudine therapy for hepatitis B virus (HBV)-infected patients resistant to Ramivudine. Patients and methods Among 17 studied patients, 7 had chronic active HBV infection and 10 were posttransplant with HBV infection (9 with de novo HBV). They received lamivudine plus adefovir therapy for 2 years. We assessed reductions in serum HBV-DNA and alanine aminotransferase (ALT) levels, loss of HBeAg (in HBeAg+ cases), and HBsAg clearance. Results A virological response, as defined by HBV-DNA below the cut off by hybridization, was observed in 12 (70.6%) patients and loss of HBeAg in 4 (44.4%) of the 9 initially HBeAg-positive cases. A biochemical response, defined as a decreased serum ALT to the normal range, occurred in 4 (26.7%) patients. Median serum creatinine increased in 3 of 15 (20%) patients, excluding those on hemodialysis. There were two noteworthy cases of sustained HBsAg seroconversion with adefovir (11.8%): one patient with de novo HBV infection posttransplantation and positive hepatitis C virus–RNA serology, and one patient with decompensated HBV cirrhosis in whom viral replication ceased, making him eligible for transplantation. Conclusions Currently, adefovir is an effective rescue therapy that broadens the existing range of options for patients with lamivudine-resistant chronic hepatitis B infection, particularly those with decompensated cirrhosis awaiting a liver graft, and those with recurrent posttransplantation HBV. The relatively small biochemical response seen in these patients may be attributable to the high prevalence of concomitant hepatitis C virus infection (41%).

Background Acute humoral rejection (AHR) is characterized by acute graft dysfunction associated with de novo production of donor-specific alloantibodies (DSA) and C4d deposition in peritubular capillaries of the renal allograft. It has been reported the combination of plasmapheresis (PP) and intravenous gamma globulin (IVIG) as effective rescue therapy for established AHR. Methods Between 1999 and 2004, seven kidney allografts recipients suffered from AHR diagnosed by severe rejection and C4d staining in peritubular capillaries. All patients had a negative cross-match before renal transplantation. Results All patients were treated with daily sessions of PP and in four cases IVIG was added after the last PP session. Tacrolimus and mycophenolate mofetil were employed as maintenance immunosuppressive regimen. In one case, rituximab was added to PP and IVIG owing to refractory humoral rejection. At 1 year, patient survival was 100%, allograft survival was 70%, and the mean serum creatinine was 201 μmol/L. Conclusions AHR is a severe form of rejection associated with a poor prognosis, but its early diagnosis and treatment with PP and IVIG allows reversal of AHR reaching a 70% graft survival at 1 year.

In renal transplantation, chronic allograft nephropathy is the leading cause of long-term graft losses, transplant glomerulopathy being its glomerular form. Differential diagnosis from recurrent or de novo membranoproliferative glomerulonephritis should be established. Whether hepatitis C virus is associated with cryoglobulinemia and glomerular damage in renal allograft recipients, as in native kidneys, is not known. We identified six hepatitis C virus-infected renal allograft recipients with proteinuria higher than 1.5 g/day, microhematuria, and membranoproliferative glomerulonephritis. Virologic and immunologic studies were conducted. Low serum levels of circulating immune complexes and cryoglobulins were observed, which were type II immunoglobulin G polyclonal-immunoglobulin Mk monoclonal in all six patients. Classical serum complement pathway activation and at least one type of autoantibodies were present in all of them. Hepatitis C virus RNA was found in higher concentrations in cryoprecipitate than in serum (percentage of enrichment ranged from 341 to 18,200%). Hepatitis C virus genotype was 1b in 4 of 6 patients, 1a in 1 of 6 patients, and 2a in 1 of 6 patients. In renal histology prominent parietal diffuse deposition of immunoglobulin M was the rule. Glomerular subendothelial electron-dense deposits with fibrillar appearance were observed in the two patients in which electron microscopy provided information about glomeruli. In renal allograft recipients hepatitis C virus infection may be associated with type II cryoglobulinemia which may lead to membranoproliferative glomerulonephritis. Immunologic and virologic studies may help to differentiate hepatitis C virus-associated membranoproliferative glomerulonephritis from transplant glomerulopathy.

The renal preservation ability of a flushing solution (F-M) with fructose-1,6-diphosphate (1 g/dl) and mannitol (2 g/dl) during cold ischaemia was studied with the isolated perfused rat kidney model and compared with the Euro-Collins (EC) and University of Wisconsin (UW) solutions. Kidneys were stored in hypothermia for 4 and 18 h after initial flushing with the solution being tested, and then reperfused at 37 degrees C in an isolated perfusion circuit for 90 min with a Krebs-Henseleit solution containing 4.5% albumin. Forty-four kidneys were studied and divided in a control group and six study groups according to the cold ischaemia time and flushing solution used. Renal functional parameters of plasma flow rate (PFR), renal vascular resistance (RVR), urine flow rate (UFR) glomerular filtration rate (GFR), fractional (FRNa) and net (TNa) sodium reabsortion were assessed during reperfusion. Conventional histology and malondialdehyde tissue levels (MDA) were also evaluated. Our results show that PFR, RVR, and UFR were similar in all study groups. After 4 and 18 h of cold ischaemia, GFR, FRNa and TNa were better, and conventional histology worse in F-M than in EC flushed kidneys. After 4 and 18 h of cold ischaemia, GFR, FRNa and TNa, in fact, were not different between F-M and UW flushed kidneys. After 4 h of cold ischaemia, conventional histology was similar in F-M and UW flushed kidneys. Nevertheless, after 18 h of cold ischaemia, UW flushed kidneys showed worse histological parameters than F-M flushed kidneys. After 4 h of cold ischaemia, MDA was similar in kidneys flushed with three solutions. After 18 h of cold ischaemia MDA was higher in EC than in F-M or UW flushed kidneys. In summary, our newly developed cold storage solution shows promising results in renal preservation and its ability to preserve is at least as good as UW solution assessed in the isolated perfused rat kidney.

Protocol biopsies performed in stable renal allografts show different degrees of acute and chronic lesions. Histologic findings in protocol biopsies have been related to graft outcome. We evaluated histologic lesions observed in protocol biopsies performed in patients under different immunosuppression therapies. From June 1988 a protocol biopsy was performed at approximately 4 months in patients who fulfilled the following criteria: serum creatinine

Cytomegalovirus (CMV) infection remains a major problem in renal transplant recipients. CMV produces not only febrile syndromes and/or visceral disease but also contributes to the development of acute rejection and chronic graft failure. Valganciclovir prophylaxis has represented a major advance in controlling this infection, but late CMV infection after prophylaxis can occur, especially when universal prophylaxis is used. The use of valganciclovir prophylaxis for 200 days is more effective than prophylaxis for 100 days but does not completely prevent this problem. Prophylaxis based on the detection of CMV viremia (early prophylaxis or preemptive therapy) may prevent the development of delayed CMV disease, but has the disadvantage of requiring more intensive monitoring of viremia and does not prevent the development of viremia and its potential consequences in the long term. This article reviews current recommendations for prophylaxis of CMV disease in renal transplantation.

Producción Científica, Background. To describe the causes of graft loss, patient death and survival figures in kidney transplant patients in Spain based on the recipient’s age. Methods. The results at 5 years of post-transplant cardiovascular disease (CVD) patients, taken from a database on CVD, were prospectively analysed, i.e. a total of 2600 transplanted patients during 2000–2002 in 14 Spanish renal transplant units, most of them receiving their organ from cadaver donors. Patients were grouped according to the recipient’s age: Group A: 60 years. The most frequent immunosuppressive regimen included tacrolimus, mycophenolate mofetil and steroids. Results. Patients were distributed as follows: 25.85% in Group A (>40 years), 50.9% in Group B (40–60 years) and 23.19% in Group C (>60). The 5-year survival for the different age groups was 97.4, 90.8 and 77.7%, respectively. Death-censored graft survival was 88, 84.2 and 79.1%, respectively, and non death-censored graft survival was 82.1, 80.3 and 64.7%, respectively. Across all age groups, CVD and infections were the most frequent cause of death. The main causes of graft loss were chronic allograft dysfunction in patients 1 g at 6 months post-transplantation were statistically significant in the three age groups. The patient survival multivariate analysis did not achieve a statistically significant common factor in the three age groups. Conclusions. Five-year results show an excellent recipient survival and graft survival, especially in the youngest age group. Death with functioning graft is the leading cause of graft loss in patients >40 years. Early improvement of renal function and proteinuria together with strict control of cardiovascular risk factors are mandatory.

The advent of novel immunosuppressive strategies in renal transplantation, with immunomodulatory properties, might facilitate long-term allograft survival. T-cell depletion, costimulation-blockade and mTor inhibition have been shown to favour anti-donor hyporesponsiveness. Recently, the combination of rATG, belatacept (Bela) and sirolimus (SRL) has been used in kidney transplantation, showing very low incidence of acute rejection and excellent 12-month graft and patient survival. Herein, we have analysed the 1-year evolution of memory/effector and regulatory T cells and assessed the donor-specific T-cell alloimmune response in a group of these patients and compared with others treated with a calcineurin-inhibitor(CNI)-based (rATG/tacrolimus/MMF), and two other Bela-based regimens (rATG/Bela/MMF and basiliximab/Bela/MMF/steroids). During the first year after transplantation, patients receiving rATG/Bela/SRL had significantly higher percentage of Tregs upon the memory T-cell compartment and showed a potent anti-donor suppressive activity. In an in vitro naive and memory/effector T-cell co-culture, the combination of costimulation-blockade and SRL could abrogate both antigen-specific T-cell responses as efficiently as using a CNI drug. The combination of T-cell depletion, costimulation-blockade and mTor inhibition seems to be able to allow Treg survival and inhibit donor-specific alloreactive effector immune responses after kidney transplantation in humans.

Introduction A 66-year-old white Caucasian man was admitted to our hospital 21 weeks after renal transplantation for the evaluation of mild heart failure, low-grade fever Visceral leishmaniasis is an endemic parasitic infection in the Mediterranean area [1]. Shortly after the initial and weight loss. Before renal transplantation, he had been treated with haemodialysis for a period of 3 infection, the parasite spreads through the monocyte macrophage system and a granulomatous cellular years for end-stage renal disease of unknown aetiology. Immunosuppression for renal transplantation conimmune response develops, leaving the parasite in a latent form. Therefore, hosts may remain free of clinsisted of a monotherapy with cyclosporin A (Sandimmun NeoralB). The early post-transplantation ical symptoms for long periods of time. Although impairment of cellular immunity could trigger overt period was uneventful and he was discharged 9 days later with a serum creatinine of 150 mmol/l. During the disease, visceral leishmaniasis is uncommon in allograft recipients, even in endemic areas. However, immunofirst 3 months, he experienced three episodes of graft rejection, which were each treated with three pulses of compromised hosts have a worse outcome since the disease behaves more aggressively. These individuals 500 mg/day of 6-methylprednisolone. After the last graft rejection episode (8 weeks before admission), have an atypical clinical presentation and course of disease, which may delay the diagnosis, and they 1.5 g/12 h of mycophenolate mofetil were added to the immunosuppression regime. Serum creatinine at his respond more poorly to therapy [2,3]. Pentavalent antimonial drugs have been classically discharge was 398 mmol/l. On admission, physical examination revealed paleconsidered the therapy of choice, but the frequency of serious adverse events and the increasing incidence of ness, tachycardia, a few basilar rales and peripheral pitting oedema. A grade 2 soft systolic murmur was primary parasitic resistance or relapses have stressed the need for alternative treatments. However, informaheard along the lower left sternal border. No diastolic murmur or pericardial friction rub was detected. tion is insufficient and an optimal therapeutic regime lacking adverse effects has not yet been described Abdominal examination revealed a firm and nontender 8-cm splenomegaly and a normal renal allograft. should any problem occur [4]. We report the case of a renal allograft recipient with Funduscopic examination was normal. Thoracic radiographs showed a mild cardiac enlargement and visceral leishmaniasis who developed acute pancreatitis during the initial phase of treatment with meglumine some fluid in fissures. Laboratory tests revealed: serum creatinine 292 mmol/l (creatinine clearance: antimoniate. We then successfully treated the patient using a novel combination of ketoconazole and allopu18 ml/min/1.73 m2); urea nitrogen (BUN) 10.9 mmol/l; whole-blood cyclosporin levels 102 ng/ml (RIA specific monoclonal antibody, CYCLO-Trac-SP, Incstar, Stillwater, MN); serum alanine aminotransferCorrespondence and offprint requests to: Josep M. Grinyo MD, ase 0.17 mkat/l; serum albumin 34 g/l; serum total Department of Nephrology, Hospital de Bellvitge, C. Feixa Llarga s/n, 08907 L’Hospitalet, Barcelona, Spain. proteins 51 g/l; serum protein electrophoresis a1

Producción Científica, To evaluate cardiovascular disease (CVD) after renal transplantation we established a CVD database (no-intervention) including all patients transplanted among 2000–2002 in 14 hospitals from Spain (Renal Forum Group) (n¼2600). They were prospective followed annually thereafter and we present herein the most important results concerning survival figures and CVD at four years. Mean recipient age was 49.7±13.7 years: 16% retransplanted and 12.5% hyperimmunized. Tacrolimus, mycophenolate mofetil, and steroids was used in 63%. Acute rejection (AR) rate at 1 year was 14.8%. Graft and patient survival at 48 months were 85.6% (death censored) and 91.7% respectively. The first cause of graft loss was vascular in the first year, death with function during the 2–3 years, and chronic allograft nephropathy at the 4th year. Donor age, time on dialysis, acute tubular necrosis (ATN), AR, SCr at 6 months, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in the first year, and systolic blood pressure at 24 months were independent risk factors for graft loss at 4th year. The first cause of death was CVD (predominantly ischemic heart disease (IHD) in the first year). Recipient age, ATN, and SCr at 6 months were independent predictors of mortality. Despite worsening of donor age, comorbidity, and advanced age of recipients, survival figures at four years are considered good in our Spanish non-selected population. Cardiovascular mortality is the most important cause of death and graft loss particularly, IHD in the first year. Therefore, to decrease post-transplant mortality a careful cardiovascular evaluation and treatment in the waiting list and a close follow-up of patients after transplantation is mandatory.

Our work is based on 11 field notebooks with his notes and descriptions of macroscopic and microscopic anatomic preparations. There is also one notebook with several handmade drawings on black lead pencil, reproducing the microscopic anatomy of the bladder neck; there are also five 60 x 40 cm prints with histologic drawings, several histologic preparations, as well as several letter papers with Dr. Salvador's letterhead in his various institutional aspects.

Introduction and Methods An epidemiologic multicenter study was performed to evaluate the prevalence and management of gastrointestinal (GI) complications in solid organ transplant patients. A total of 1788 recipients were included, 1132 of which corresponded to renal transplanted patients. Results The mean age for the renal transplanted patients was 52 ± 13.2 years. The mean time from the transplantation was 5.4 ± 5.4 years. 17.7% showed some pretransplant GI disease, while 53% presented this type of complication in the posttransplant period. Diarrhea was the most prevalent GI complication (51.5%) and digestive perforation was the GI disorder that affected the patients daily living the most. From the patients with GI complications, 71% received pharmacological treatment, using gastric protectors in 91.3% of the cases. Regarding immunosuppressive drugs, in 30.9% of the cases the dose of the drug was reduced, in 9.3% discontinued temporarily and in 7.5% discontinued permanently. These changes mainly affected the MMF (89%, 83% and 74% for dose change, temporary and permanent discontinuation, respectively). Conclusions The prevalence of GI complications in renal transplant exceeded 50%, and affected patients’ daily living. The management of these complications was based on treatment with gastric protectors, dose reduction and/or partial or definitive MMF discontinuation.

Immunosuppressive protocols in dual kidney transplantation (DKT) are based on calcinerurin inhibitors (CNI). We wonder whether a CNI-free immunosuppression can improve outcome in older patients receiving a DKT with marginal donor organs. Thirty-six were treated with CsA, MMF and prednisone (CsA group) and 42 with rATG, SRL, MMF and prednisone (SRL group). Incidence of delayed graft function and acute rejection was 44% and 11% in the CsA group, and 40% and 8% in the SRL group. CMV infection incidence was low in both protocols. Three-year patient survival was 89% in the CsA and 76% in the SRL group. One- and 3-year graft survival after censoring for dead with a functioning allograft was 94.2% and 94% in CsA and 95% and 90% in SRL, respectively. Renal function was similar in both groups whereas proteinuria was higher in the SRL group. Uninephrectomy due to graft thrombosis or urinary-related complications was numerically higher in the SRL (21%) than in the CsA group (8%) (p = 0.13) and it was associated with renal failure and proteinuria. In DKT, a new induction immunosuppressive protocol based on rATG, SRL, MMF and prednisone does not offer any advantage in comparison to the old CsA, MMF and prednisone.

Chronic allograft nephropathy (CAN) in protocol biopsies is associated with graft loss while the association between subclinical rejection (SCR) and outcome has yielded contradictory results. We analyze the predictive value of SCR and/or CAN in protocol biopsies on death-censored graft survival. Since 1988, a protocol biopsy was done during the first 6 months in stable grafts with serum creatinine