Pre-Transplant Assessment of Vascular Calcification as a Risk Factor of Mortality, Graft Loss, and Cardiovascular Events in Renal Transplant Recipients.

BACKGROUND: Vascular calcification (VC) is known as an independent predictor of mortality in patients undergoing hemodialysis; nevertheless, there is a lack of studies about the impact of vascular calcification in renal transplant recipients, and none of them use the Kauppila Index (KI) as a predictor of patient and graft prognosis. METHODS: We conducted an observational, retrospective study of 119 renal transplants, evaluating abdominal aortic calcifications (L4-S1) with the KI. We established 2 categories: absence (KI = 0-2) and presence (KI = 3-24) of VCs before transplantation. We analyzed the impact of calcification in graft and patient survival, new-onset diabetes mellitus, hypertension, cardiovascular events, renal function, and mineral metabolism. RESULTS: VCs were observed in 50 patients (42%) before renal transplantation. Patients with VCs were older, but no statistical differences were found in the pre-transplant study between sex, diabetes, body mass index, and cardiovascular events. We found a major patient survival (limited to first 2 years after transplantation), graft survival, and death-censored graft survival in those without VCs (P = .037, P = .015, and P = .023, respectively). In line with results, a higher incidence of major cardiovascular events (MACE) and cardiovascular death was observed in the group with preexisting calcification (P = .016/P = .019). In the multivariable analysis, VCs were not an independent predictor for graft loss, death-censored graft loss, or major cardiovascular events. CONCLUSIONS: Simple evaluation of VCs with the use of the KI at the time of transplantation relates with graft and patient survival and with MACE after renal transplantation.

The role of transmembrane protein 27 (TMEM27) in islet physiology and its potential use as a beta cell mass biomarker.

AIMS/HYPOTHESIS: Transmembrane protein 27 (TMEM27) is a membrane protein cleaved and shed by pancreatic beta cells that has been proposed as a beta cell mass biomarker. Despite reports of its possible role in insulin exocytosis and cell proliferation, its function in beta cells remains controversial. We aimed to characterise the function of TMEM27 in islets and its potential use as a beta cell mass biomarker. METHODS: To determine TMEM27 function, we studied TMEM27 gene expression and localisation in human healthy and diabetic islets, the correlation of its expression with cell cycle and insulin secretion genes in human islets, its expression in tungstate-treated rats, and the effects of its overproduction on insulin secretion and proliferation in a beta cell line and islets. To elucidate its utility as a beta cell mass biomarker, we studied TMEM27 cleavage in a beta cell line, islets and primary proximal tubular cells. RESULTS: TMEM27 mRNA levels in islets are lower in diabetic donors than in controls. Its gene expression correlates with that of insulin and SNAPIN in human islets. TMEM27 expression is downregulated in islets of tungstate-treated rats, which exhibit decreased insulin secretion and increased proliferation. TMEM27 overproduction in a beta cell line and islets significantly enhanced glucose-induced insulin secretion, with modest or no effects on proliferation. Finally, TMEM27 is cleaved and shed by renal proximal tubular cells and pancreatic islets. CONCLUSIONS/INTERPRETATION: Our data support a role for TMEM27 in glucose-induced insulin secretion but not in cell proliferation. The finding that its cleavage is not specific to beta cells challenges the current support for its use as a potential beta cell mass biomarker.

Trasplante renal ABO incompatible: de un sueño a una realidad. Experiencia del Hospital Clínic de Barcelona / ABO incompatible living donor kidney transplantation: a dream come true. Experience of Hospital Clínic of Barcelona

Introducción: En los últimos años se ha mantenido estable el número de pacientes en lista de espera para un trasplante renal. El trasplante renal de donante vivo representa actualmente una vía para aumentar el pool de donantes, pero hay un grupo de pacientes que presentan incompatibilidad de grupo sanguíneo ABO, lo que contraindicaba hasta ahora que pudiera llevarse a cabo el trasplante. Nuestro objetivo consiste en describir nuestra experiencia con el programa de trasplante renal de donante vivo con incompatibilidad de grupo ABO. Material y métodos: Se trata de un estudio de retrospectivo-descriptivo de los primeros 11 pacientes sometidos a trasplante renal de donante vivo ABO incompatible en el Hospital Clínic de Barcelona desde octubre de 2006 a enero de 2009. Se utilizó un protocolo de acondicionamiento basado en inmunoadsorción específica (con número sesiones necesarias hasta conseguir títulos de isoaglutininas aceptables pretrasplante), inmunoglobulina policlonal inespecífica y anticuerpo monoclonal anti-CD20, seguido del tratamiento inmunosupresor adaptado a cada receptor. Se determinaron títulos de isoaglutininas antes del tratamiento de acondicionamiento, pretrasplante y postrasplante durante las primeras 2 semanas. La valoración inmunológica, médica y quirúrgica fue la habitual en el programa de trasplante renal de donante vivo. Resultados: La edad media de los donantes y receptores fue de 47,8 ± 12,4 y 44,4 ± 14,1 años, respectivamente. Un 90,1% de los donantes fue mujer y un 72,7% de los receptores, hombres. El tiempo de seguimiento medio fue de 10,2 ± 10,2 meses. Hermanos y esposos fueron las relaciones más frecuentes (n = 4, 36,4%, respectivamente), al igual que la causa de nefropatía fueron la glomerulopatía, poliquistosis y el síndrome de Alport (n = 2, 18,2% para cada enfermedad renal primaria). Todos los pacientes adquirieron un título de isoaglutininas correctos pretrasplante (<8) y requirieron 5,54 ± 2,6 sesiones de inmunoadsorción pretrasplante y 2,82 sesiones postrasplante. Un paciente no requirió ninguna sesión de inmunoadsorción (única con incompatibilidad anti-B) y otro requirió recambios plasmáticos, en vez de inmunoadsorciones, por tratarse de un potencial receptor hipersensibilizado con crossmatch por citometría de flujo positivo. Los títulos de isoaglutininas postrasplante se mantuvieron a títulos bajos. Dos pacientes presentaron un episodio de rechazo agudo celular (Banff IA e IB), con buena respuesta al tratamiento. La supervivencia de paciente y del injerto fue de un 90,9% en el primer año y se mantuvo estable a lo largo del seguimiento. Únicamente se registró una pérdida del injerto por fallecimiento en relación con una complicación hemorrágica en las primeras 72 horas sin relación con la incompatibilidad de grupo ABO. La función de injerto renal al año es excelente, con valores de creatinina sérica de 1,3 ± 0,8 mg/dl, con aclaramiento de creatinina ajustado a superficie corporal 62,6 ml/min/1,73 m2 y proteinuria de 244,9 mg/orina de 24 horas. Conclusiones: El trasplante renal de donante vivo con incompatibilidad de grupo sanguíneo representa una alternativa eficaz y segura en determinados pacientes en lista de espera de trasplante renal, obteniendo resultados excelentes de supervivencia de paciente e injerto y con una buena función de injerto renal (AU)

Introduction: During the last years the number of patients on waiting list for kidney transplantation has been stable. Living donor kidney transplantation is nowadays a chance to increase the pool of donors. However, there are a group of patients with ABO incompatibility, making impossible the transplant until now. The aim of the present study is to describe the experience of Hospital Clinic Barcelona on ABO incompatible living transplantation. Material and methods: A retrospective-descriptive study was made based on 11 living donor kidney recipients with ABO incompatibility in Hospital Clinic of Barcelona from October’06 to January’09. Selective blood group, antibody removal with specific immunoadsortion, immunoglobulin and anti-CD20 antibody were made until the immunoglobulin (IgG) and isoaglutinine (IgM) antibody titters were 1/8 or lower. Immunosuppressive protocol was adjusted to particular recipient characteristics. Isoaglutinine titters were set before, during and post desensitization treatment and two weeks after transplant. Immunological, medical and surgical evaluation was the standard in living donor kidney transplant program. Results: Medium age of donors and recipients were 47.8 ±12.4 and 44.4 ± 14.1 years, respectively. 90% of donors were females and 73% of recipients males. Follow-up time was 10.2 ±10.2 months. Siblings and spouses were the most frequent relation (n = 4, 36.4%, respectively). Chronic glomerulonephritis, adult polycystic kidney disease and Alport syndrome, the most frequent cause of end-stage renal disease. All the patients acquire appropriate isoaglutinine titters pre transplant (<1/8), requiring 5.54 ± 2.6 immunoadsorption sessions pretransplant and 2.82 postransplant. One patient didn´t need any immunoadsorption session (incompatibility blood group B) and another patient plasma exchange instead of immunoadsorption for being hipersensitized with positive flow cytometry crossmath. Postransplant isoaglutinine titters remained low. Two patients had cellular acute rejection episode (type IA and IB of Banff classification) with good response to corticosteroid treatment. Patient and graft survival were 91% at first year and remain stable during the follow-up. A graft lost by death of patient in relation to haemorrhagic shock developed within the first 72 hours after transplantation. Renal graft function at first year was excellent with serum creatinina of 1.3 ± 0.8 mg/dl, creatinine clearance of 62.6 ml/min/1.73 m2 and proteinuria of 244.9 mg/U 24 h. Conclusion: ABO incompatible living donor kidney transplantation represent an effective and safe alternative in certain patients on waiting list for renal transplant, obtaining excellent results in patient and graft survival, with good renal graft function (AU)

[ABO incompatible living donor kidney transplantation: a dream come true. Experience of Hospital Clínic of Barcelona]. / Trasplante renal ABO incompatible: de un sueño a una realidad. Experiencia del Hospital Clínic de Barcelona.

INTRODUCTION: During the last years the number of patients on waiting list for kidney transplantation has been stable. Living donor kidney transplantation is nowadays a chance to increase the pool of donors. However, there are a group of patients with ABO incompatibility, making impossible the transplant until now. The aim of the present study is to describe the experience of Hospital Clinic Barcelona on ABO incompatible living transplantation. METHODS: A retrospective- descriptive study was made based on 11 living donor kidney recipients with ABO incompatibility in Hospital Clinic of Barcelona from October'06 to January'09. Selective blood group, antibody removal with specific immunoadsortion, immunoglobulin and anti- CD 20 antibody were made until the immunoglobulin (IgG) and isoaglutinine (IgM) antibody titters were 1/8 or lower. Immunosuppressive protocol was adjusted to particular recipient characteristics. Isoaglutinine titters were set before, during and post desensitization treatment and two weeks after transplant. Immunological, medical and surgical evaluation was the standard in living donor kidney transplant program. RESULTS: Medium age of donors and recipients were 47.8 +/- 12.4 and 44.4 +/- 14.1 years, respectively. 90% of donors were females and 73% of recipients males. Follow-up time was 10.2 +/- 10.2 months. Siblings and spouses were the most frequent relation (n=4, 36.4%, respectively). Chronic glomerulonephritis, adult polycystic kidney disease and Alport syndrome, the most frequent cause of end-stage renal disease. All the patients acquire appropriate isoaglutinine titters pre transplant (< 1/8), requiring 5.54 +/- 2.6 immunoadsorption sessions pretransplant and 2.82 posttransplant. One patient didn t need any immunoadsorption session (incompatibility blood group B) and another patient plasma exchange instead of immunoadsorption for being hypersensitized with positive flow cytometry crossmatch. Posttransplant isoaglutinine titters remained low. Two patients had cellular acute rejection episode (type IA and IB of Banff classification) with good response to corticosteroid treatment. Patient and graft survival were 91% at first year and remain stable during the follow-up. A graft lost by death of patient in relation to haemorrhagic shock developed within the first 72 hours after transplantation. Renal graft function at first year was excellent with serum creatinine of 1.3 +/- 0.8 mg/dl, creatinine clearance of 62.6 ml/min/1.73 m2 and proteinuria of 244.9 mg/U-24h. CONCLUSION: ABO incompatible living donor kidney transplantation represent an effective and safe alternative in certain patients on waiting list for renal transplant, obtaining excellent results in patient and graft survival, with good renal graft function.

Conversion from tacrolimus to cyclosporine could improve control of posttransplant diabetes mellitus after renal transplantation.

Posttransplant diabetes mellitus (PTDM) occurs in approximately 15% to 20% of renal transplant patients. It has important clinical implications for graft function and survival. Anticalcineurin drugs are associated with an increased risk of developing PTDM. There is a little evidence that conversion from tacrolimus to cyclosporine (CsA)-based immunosuppression improves glucose metabolism and reverses diabetes. This prospective study included nine renal transplant patients (mean age of 34 +/- 20) with PTDM under immunosuppression with tacrolimus. Five were switched directly to CsA and the other four (glycemia > 250 mg/dL) required insulin and were simultaneously switched to CsA. Basal blood levels of tacrolimus were 7.9 +/- 1.9 ng/dL. Conversion was associated with an early, significant improvement of glycemia and HbA1c blood levels (P < .01). At the end of the follow-up, the glycemia (105 +/- 20 mg/dL) and Hb1Ac (5.1 +/- 0.4 mg/dL) were normal. Insulin was discontinued between 3 and 6 months in all patients who required it at the beginning. Cholesterol did not change significantly and triglycerides decreased significantly (basal 210 +/- 85 mg/dL, at 12 months 125 +/- 29, P < .01). Graft function was stable with a mean serum creatinine of 1.7 +/- 0.2 mg/dL. CsA blood levels remained stable during all follow-up periods (P = NS). There were neither episodes of acute rejection nor secondary effects related to the medication. In summary, renal transplant patients receiving tacrolimus who develop PTDM may display better control of hyperglycemia by a switch to CsA.

Efficacy of conversion to sirolimus in posttransplantation Kaposi's sarcoma.

UNLABELLED: The increased incidence of Kaposi's sarcoma (KS) in organ transplantation has been related to the KS herpes virus and the permissive effect of immunosuppressive therapy. We postulated that conversion to SRL in renal recipients with KS favored regression of KS lesions without increasing the risk of graft rejection. METHODS: In this study we performed a retrospective chart review of 7 caucasian renal transplant recipients affected by KS to determine demographic data, etiology of ESRD, immunologic risk factors, immunosuppressive treatment, KS disease follow-up, and renal function before and after SRL conversion. RESULTS: All seven patients were under calcineurin inhibitor treatment at the onset of KS which was limited to the skin, without regression despite attempts to minimize immunosuppression. After conversion to SRL, six patients showed progressive regression of KS lesions, with only hyperpigmented atrophic cutaneous lesions remaining after a mean time of 8.1 months (2-18 months). The seventh patient has completed 9 months follow-up with a near complete regression of KS lesions. One patient returned to hemodialysis after 13 months following irreversible acute renal failure not directly related to SRL conversion; in the other six, renal function was stable. The mean serum creatinine was 1.87 +/- 0.64 versus 1.74 +/- 0.68 mg/dL, pre-conversion versus the end of follow up, respectively. Mean SRL blood level was 9.2 +/- 2.0 ng/mL. CONCLUSION: After SRL conversion, patients with KS showed progressive regression without an increased risk of acute rejection. SRL offers a promising approach to the management of posttransplantation KS and probably other malignancies in organ transplant recipients.

[Evaluation of food intake in hemodialysis using a food consumption and appetite questionnaire]. / Valoración de la ingesta en hemodiálisis mediante un cuestionario de consumo alimentario y apetito.

Protein calorie malnutrition is a common complication in chronic hemodialysis patients (CHP). Although many factors could promote malnutrition, inadequate nutrient intake seems to be one of the most important. An Appetite and Diet Assessment Questionnaire (ADAQ) was developed, and we have performed a cross-sectional study in 44 CHP to investigate its capacity to predict an inadequate intake. Dietary evaluation was based on a diet diary-assisted recalls (DDAR). On the other hand, the validity of PCR and the differences in the DDAR and ADAQ between the days of dialysis and the days without dialysis were studied. The predictive value of inadequate intake of the ADAQ and the PCR were analysed with the ROC curve. The protein intake was 1.3 +/- 0.3 g/kg/day and the energy intake 29.2 +/- 0.6 kcal/kg/day. The average PCR was 1.14 +/- 0.3. The ROC curve to predict inadequate intake from the ADAQ shows an area under the curve of 0.84 for the protein intake and 0.73 for the energy intake. A cut-off ponit of 18 gives a sensitivity of 100% and a specificity of 44% for the detection of poor protein intake (< 1.2 g/kg/day) and of 74% and 56% for the detection of poor energy intake (< 30 kcal/kg/day). The ROC curve to predict inadequate protein intake from the PCR obtains an area under the curve of 0.81. The cut-off 1.06 gives the best sensitivity (100%) and specificity (64%) for the detection of insufficient protein intake. We did not find any significant difference in the DDAR or in the ADAQ between the days of dialysis and the days without dialysis. Despite the subjective interpretation, the relationship between ADAQ and protein-energy intakes analysed by DDAR was highly significant. The questionnaire is simple and can therefore be used as a screening rest to detect and correct alterations in the diet which could otherwise lead to malnutrition. The determination of PCR gives a good sensitivity and specificity for the detection of poor protein intake, although the results are modified in anabolic or catabolic states which can clinically go undetected. We do not register differences in diet between the days of dialysis and the days without dialysis.

Valoración de la ingesta en hemodiálisis mediante un cuestionario de consumo alimentario y apetito / Evaluation of nutrient intake in hemodialysis patients validity of an appetite and diet assessment and of protein catabolic rate determination

Dentro del origen multifactorial de la malnutrición en hemodiálisis periódica (HDP) la ingesta inadecuada es una causa importante, valorándose habitualmente mediante registro de consumo alimentario (RCA). Con el objetivo de detectar de forma sencilla y rápida una pobre ingesta, se desarrolla un Cuestionario de Consumo Alimentario y Apetito (CCAA) y se estima su capacidad para predecir un aporte proteico-calórico inadecuado, tomando como patrón de referencia el RCA. Así mismo se analiza la capacidad predictiva de insuficiente ingesta proteica que ofrece la tasa de catabolismo proteico (PCR) y se estudia si existen diferencias en los valores del RCA y del CCAA entre los días de diálisis y los días sin diálisis. Se incluyen en el estudio 44 pacientes en HDP en situación clínica estable. Para la evaluación de la ingesta se utilizó el método de RCA mixto (mediante pesada y entrevista) de dos días (uno de diálisis y uno de no diálisis). Se determinó el PCR y se desarrolló el CCAA, un cuestionario de 34 ítems acerca de la adecuación de la dieta y el nivel de apetito. Se realiza una baremación del CCAA y se constrastan estos datos y los valores del PCR con el RCA mediante el análisis de curva ROC. La ingesta proteica media fue de 1,3 ñ 0,3 g/kg/día y la calórica de 29,2 ñ 6 kcal/kg/día según RCA. El PCR medio fue de 1,14 ñ 0,3. Al relacionar el CCAA con el RCA obtenemos un área bajo curva de 0,84 (IC 0,70-0,93) para la ingesta proteica y de 0,73 (IC 0,57-0,85) para la calórica. El punto de corte en 18 ofrece unos valores de sensibilidad del 100 por ciento y especificidad del 44 por ciento para la detección de pobre ingesta proteica (< 1,2 g/kg/día) y del 74 por ciento y 56 por ciento para la detección de pobre ingesta calórica (< 30 kcal/kg/día). Al relacionar el PCR con la ingesta proteica según RCA obtenemos un área bajo curva de 0,81 (IC 0,660,91). El puto de corte en 1,06 nos ofrece la mejor sensibilidad (100 por ciento) y especificidad (64 por ciento) en la detección de ingesta proteica insuficiente. No encontramos diferencias significativas entre los días de diálisis y los días sin diálisis en el RCA ni en el CCAA. Consideramos que el CCAA, a pesar de la subjetividad de su interpretación, se correlaciona bien con la ingesta alimentaria analizada mediante RCA. Su realización es sencilla, por lo que puede utilizarse de forma repetitiva como screening para detectar y corregir de forma precoz alteraciones en la ingesta alimentaria que pueden conducir a déficits nutricionales. La determinación del PCR presenta una buena sensibilidad y especificidad en la detección de pobre ingesta proteica, aunque sus resultados se alteran ante estados anabólicos o catabólicos que clínicamente pueden pasar desapercibidos. No registramos diferencias en la dieta entre los días de diálisis y los días sin diálisis (AU)