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Resumen Antecedentes A pesar del uso de estrategias de prevencion y la mejora en los metodos diagnosticos, el citomegalovirus (CMV) continua siendo la complicacion viral mas frecuente despues del trasplante renal y su impacto en los resultados a largo plazo se sigue debatiendo. Objetivo Conocer la incidencia de infeccion/enfermedad por CMV bajo estrategias de prevencion y analizar su asociacion con la supervivencia del paciente y del injerto y con otros eventos clinicos relacionados con el CMV. Metodos Revision de las historias clinicas de 377 pacientes trasplantados de rinon entre enero de 1998 y diciembre del 2008. Se analizo la supervivencia por el metodo de Kaplan-Meier en funcion de la presencia o ausencia de infeccion/enfermedad CMV y se uso el modelo de Cox para identificar factores asociados con infeccion/enfermedad por CMV y para evaluar su impacto en la mortalidad y la perdida del injerto. Resultados La incidencia de infeccion por CMV fue del 34,7% y de enfermedad del 9,5%. La supervivencia del paciente y del injerto fue significativamente inferior en los pacientes con infeccion/enfermedad CMV. La infeccion/enfermedad por CMV se asocio de forma significativa a mayor riesgo de perdida del injerto (HR 1,91, IC del 95% 1,09-3,36, p = 0,023) pero no con mas riesgo de mortalidad (HR 1,29, IC del 95% 0,7-2,38, p = 0,4). Conclusion La replicacion viral despues del trasplante es un factor de riesgo de perdida del injerto pero no de mortalidad a largo plazo. Las estrategias de prevencion disminuyen la incidencia de infeccion y enfermedad por CMV postrasplante.

Background Cytomegalovirus (CMV) infection is an ongoing clinical problem in solid-organ transplantation (SOT). Pretransplant CMV serology is currently the only tool for assessing the risk of CMV infection, although cellular immune responses driven by CMV-specific CD4 and CD8 T lymphocytes are important for controlling viral replication. Therefore, the analysis of CMV-specific T cells may be useful for estimating the risk of infection. Methods This is a prospective study of patients with kidney transplants and no prophylactic treatment for CMV replication. CD4 and CD8 T-cell responses to the major CMV pp65 and IE-1 antigens in 15 seropositive patients at intermediate risk of CMV infection were investigated, according to current algorithms. Intracellular flow cytometry was employed to determine IFN-γ production as a functional readout. The response was analyzed in pretransplant samples and prospectively at 1 and 6 months and at 1 year posttransplant. Results It was observed that the CD8 responses to IE-1 antigen were practically absent pretransplant in patients who developed CMV infection posttransplant. Within the group of patients free of infection, CD8 responses to IE-1 were detected more frequently and were significantly higher (P=0.0083). In a receiver operating characteristics curve analysis (AUC=0.929; P=0.010; 95% CI: 0.078-1.0), low CD8 responses to IE-1 (≤0.05%) pretransplant predicted the development of CMV infection under the immunosuppressive regime after transplant with 100% specificity and 85.7% sensitivity. Conclusions Assessment of IE-1-specific CD8 T-cell frequencies pretransplant may be a useful tool for identifying seropositive SOT patients at risk of developing CMV infection posttransplant.

Background Kidney transplantation is the therapy of choice for end-stage kidney disease. Graft’s life span is shorter than expected due in part to the delayed diagnosis of various complications, specifically those related to silent progression. It is recognized that serum creatinine levels and proteinuria are poor markers of mild kidney lesions, which results in delayed clinical information. There are many investigation looking for early markers of graft damage. Decreasing kidney graft cortical microcirculation has been related to poor prognosis in kidney transplantation. Cortical capillary blood flow (CCBF) can be measured by real-time contrast-enhanced sonography (RT-CES). Our aim was to describe the natural history of CCBF over time under diverse conditions of kidney transplantation, to explore the influence of donor conditions and recipient events, and to determine the capacity of CCBF for predicting renal function in medium term. Patients and Methods RT-CES was performed in 79 consecutive kidney transplant recipients during the first year under regular clinical practice. Cortical capillary blood flow was measured. Clinical variables were analyzed. The influence of CCBF has been determined by univariate and multivariate analysis using mixed regression models based on sequential measurements for each patient over time. We used a first-order autoregression model as the structure of the covariation between measures. The post-hoc comparisons were considered using the Bonferroni correction. Results The CCBF values varied significantly over the study periods and were significantly lower at 48 h and day 7. Brain-death donor age and CCBF levels showed an inverse relationship (r: -0.62, p

Resumen Antecedentes: A pesar del uso de estrategias de prevención y la mejora en los métodos diagnósticos, el citomegalovirus (CMV) continúa siendo la complicación viral más frecuente después del trasplante renal y su impacto en los resultados a largo plazo se sigue debatiendo. Objetivo: Conocer la incidencia de infección/enfermedad por CMV bajo estrategias de prevención y analizar su asociación con la supervivencia del paciente y del injerto y con otros eventos clínicos relacionados con el CMV. Métodos: Revisión de las historias clínicas de 377 pacientes trasplantados de riñón entre enero de 1998 y diciembre del 2008. Se analizó la supervivencia por el método de Kaplan-Meier en función de la presencia o ausencia de infección/enfermedad CMV y se usó el modelo de Cox para identificar factores asociados con infección/enfermedad por CMV y para evaluar su impacto en la mortalidad y la pérdida del injerto. Resultados: La incidencia de infección por CMV fue del 34,7% y de enfermedad del 9,5%. La supervivencia del paciente y del injerto fue significativamente inferior en los pacientes con infección/enfermedad CMV. La infección/enfermedad por CMV se asoció de forma significativa a mayor riesgo de pérdida del injerto (HR 1,91, IC del 95% 1,09-3,36, p = 0,023) pero no con más riesgo de mortalidad (HR 1,29, IC del 95% 0,7-2,38, p = 0,4). Conclusión: La replicación viral después del trasplante es un factor de riesgo de pérdida del injerto pero no de mortalidad a largo plazo. Las estrategias de prevención disminuyen la incidencia de infección y enfermedad por CMV postrasplante. Abstract Background: Despite the use of prevention strategies, cytomegalovirus (CMV) infection is the most common viral complication after renal transplant and its impact on long-term outcomes is still open to debate. Objective: To evaluate the incidence of CMV infection and disease during the use of prevention strategies in our centre and to analyse the association between CMV infection and long-term patient and graft survival and other potentially clinical events related with CMV. Methods: We reviewed the medical records of 377 recipients of kidney transplants performed between January 1998 and December 2008. Kaplain-Meier survival curve analysis was performed to analyse graft and patient survival by CMV infection/disease and Cox proportional hazards regression was used to identify factors associated with CMV infection/disease, graft loss and mortality. Results: The incidence of CMV infection was 34.7% and CMV disease was 9.5%. Patient and graft survival was significantly lower in patients with CMV infection/disease. CMV infection/disease was associated with a higher risk of graft loss (HR 1.91, 95% CI 1.09-3.36, p = 0.023), but not with a higher mortality (HR 1.29, 95% CI 0.7-2.38, p = 0.4). Conclusion: CMV replication after renal transplant is a risk factor for long-term graft loss but not mortality. Prevention strategies decrease post-transplant CMV infection and disease.

UNLABELLED Orthotopic renal transplant (ORT) is useful in cases of severe atherosclerosis, heterotopic bilateral transplant, unsuitable pelvic vessels and in aortic thrombosis, but it is not available in all the institutions and it is only realized of exceptional form. AIM To review the indication, surgical technique and outcome of the ORT at our hospital. MATERIAL AND METHODS The studied included five cases between January 1990 and December 2005. We analyzed several variables: demographic characteristics, characteristics of the donor, ischemia times, evolution of renal function and morbi-mortality associated. RESULTS Left ORT was performed in three men and two women. Mean patient age was 52+/-5 years, all the patients received kidneys from cadaveric donors. Mean creatinine and urea one month postoperative were 2.2+/-0.72 mg/dl and 103+/-17.2 mg/dl and at 6 months postoperative were 1.8+/-0.59 mg/dl and 78+/-14 mg/dl respectively. Immediately all patients received prophylaxis with low molecular weight heparin but it was indicated antiaggregation to two patients when they left the hospital, anticoagulation to two patients and to one of them was decided to anticoagulation nor antiagregation for history of bled digestive. A patient died for bleeding episode at level of the renal graft six months after the transplant, she was in treatment with dicumarinics, they were indicated by venous deep thrombosis in right leg. The survival a year is 80 % of the graft and the patient. Only two patients returned to hospital later, one of them for presenting an episode of diverticulitis and the other one for renal obstructive failure that needed laying of catheter pig-tail. Four patients presented stenosis of renal native vassels detected in control magnetic nuclear resonance, not symptomatic. There are two patients who take more than three years transplanted with renal stable function (creatinina 1.3 mg/dl and 1.4 mg/dl respectively). CONCLUSION ORT is an excellent option in patients with co-morbidity increased for atherosclerosis and that cannot be placed in the iliac fossaes.

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

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.

BACKGROUND : Posttransplant lymphoproliferative disorders (PTLDs) are almost always of B-cell derivation and have a strong association with Epstein-Barr virus (EBV). Only rare cases of CD30 (Ki-1)-positive anaplastic large cell (ALC) lymphomas in transplant recipients have been described. EBV has been studied in few of these cases. Pleural effusion is an uncommon clinical manifestation of both PTLDs and CD30-positive ALC lymphoma. CASE: A 60-year-old, male renal transplant recipient presented with fever and pleural effusion. Cytologic examination of the effusion revealed a large cell lymphoma. Immunocytologic studies disclosed a T-cell phenotype. Subsequently a cutaneous lesion and an accessory spleen were observed, and cervical lymphadenopathies developed. Fine needle aspiration of lymph nodes confirmed the presence of lymphoma. Histologic and immunohistochemical studies of the lymph nodes, skin and accessory spleen revealed the presence of CD30-positive, T-cell, ALC lymphoma. No EBV DNA was detected by polymerase chain reaction analysis. Despite chemotherapy, the patient died seven months after the initial cytologic diagnosis of lymphoma. CONCLUSION: CD30-positive ALC lymphomas are an uncommon variant of PTLDs that should be considered in the differential diagnosis of neoplastic disorders arising in immunosuppressed patients. Cytology and immunocytochemistry are useful diagnostic procedures for their early detection.

Kidney transplantation is the best option for the treatment of end-stage renal disease in terms of survival and quality of life. These results can be influenced by the pretransplant dialysis modality. The aim of this study was to evaluate whether the pretransplantation dialysis modality influences patient and allograft survival beyond 10 years and examine the potential risk factors associated with the outcomes. We conducted an observational, retrospective, single-center clinical study that included 236 patients [118 undergoing peritoneal dialysis (PD) and 118 undergoing hemodialysis (HD)] who proceeded to transplantation during the period December 1990–2002. Donor and recipient data were collected from our hospital’s clinical registries. The follow-up period extended to the patient’s death, the loss of the allograft, or loss to follow-up. The end date of the study was set at March 2012. In the multivariate analysis, the long-term patient survival rate was higher for the PD group than for the HD group [HR = 2.62 (1.01–6.8); p = 0.04]; however, the allograft survival rate was not significantly different between the two groups [HR = 0.68 (0.41–1.10); p = 0.12]. Pretransplantation dialysis modality is associated with long-term patient survival, with outcomes favoring peritoneal dialysis over hemodialysis. However, the pretransplant dialysis modality does not influence long-term graft loss risk.

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.

Background. Renal re-transplants are increasing in number, due to many first renal transplant patients coming back to dialysis treatment. There are controversial opinions about the evolution of these re-transplanted patients. The aim of our study is to analyse the prognosis of patients and grafts under a renal re-transplant. Methods. This was a retrospective study of 579 renal re-transplants realized in 15 Spanish different centres in the years 1990, 1994, 1998 and 2002 including all renal re-transplants realized in the above-mentioned centres during the same periods. Results. During the follow-up period, 8.81% of patients died. The actuarial patient survival was 85% at 10 years and 80% at 15 years. Principal reasons of death were the same as normal for the renal transplanted patient: cardiovascular (30.77%), infectious (13.46%) and neoplastic (13.46%). During the period of follow-up, 28.6% of the grafts were lost. The actuarial graft survival was 75% at 10 years and 58% at 15 years. Causes of graft loss are very similar to those described in literature. Conclusion. Renal re-transplant is a kind of substitute renal treatment with excellent clinical results that allow to take it as a first-order modality of treatment when the first renal transplant has failed.

There is evidence showing the importance of reaching immunosuppressant target concentrations as soon as possible. The aim of this study was to evaluate the relationship between tacrolimus trough concentrations within the first week after transplantation and the rate of acute rejection. In this descriptive-analytic study, we included 57 renal transplant patients receiving tacrolimus as the primary immunosuppressive drug. After univariate analysis, donor age, duration of hospital stay, and creatinine clearance (third month) showed significant differences between rejecters and nonrejecters. In addition, mean tacrolimus trough concentrations on day 5, day 7, mean of days 1-7, and mean of days 5-7 were found to be significantly lower in rejecters (P = 0.009, P = 0.012, P = 0.006, and P = 0.035, respectively). Receiver operating characteristic curve analysis with tacrolimus trough concentrations measured on days 5 and 7 was able to discriminate between patients with and without acute rejection (P = 0.028 and P = 0.048 after Bonferroni correction). The tacrolimus trough concentration with the best sensitivity-specificity balance was 9.3 ng/mL on day 5 and 8.7 ng/mL on day 7. In the Kaplan-Meier analysis, patients with tacrolimus trough concentrations below 9.3 mg/mL on day 5 showed a lower survival time without acute rejection (P = 0.048 after correction) in comparison with patients with tacrolimus trough concentrations above this concentration. After logistic regression, we obtained a model relating rejection with sex, donor age, and tacrolimus trough concentrations on day 5 (P = 0.004). No significant relationship between tacrolimus trough concentrations and delta creatinine clearance from week 1 to month 3 was obtained. These results confirm that tacrolimus trough concentrations during the first week are an important predictor of acute rejection. Therefore, it is critical to reach target blood concentrations of tacrolimus as soon as possible to improve allograft survival.

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.

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.