Vitamin D deficiency in solid-organ transplant recipients from a Spanish Mediterranean population.

BACKGROUND: Solid-organ transplant recipients (SOTRs) are at risk of developing vitamin D deficiency, mainly caused by reduced sunlight exposure with subsequent low vitamin D synthesis in the skin. AIM: To analyse whether SOTRs from a Spanish Mediterranean region were vitamin D-deficient. METHODS: This was a cross-sectional, descriptive and observational study in a transplantation-specialized Dermatological Unit from a Mediterranean area to determine the calcidiol levels of a cohort of 78 consecutively attending patients not receiving vitamin D supplements. Serum 25(OH)D3 levels were determined and clinical characteristics were collected. Logistic regression analysis was used to analyse variables associated with dichotomized 25(OH)D3 levels (≤ or > 10 ng/mL). RESULTS: The cohort comprised 30 lung, 29 kidney and 19 liver transplant recipients. Mean calcidiol was 18 ± 9 ng/mL. Deficiency of 25(OH)D3 was present in 19% of patients, while 68% had insufficient levels and 13% had sufficient levels. Following multivariate logistic regression analysis, the season of blood sampling remained the only predictor of deficient 25(OH)D3 levels. CONCLUSION: Despite living in a mid-latitude country with sunny weather, our SOTR population was at high risk of developing hypovitaminosis D, especially in autumn/winter. Avoiding sun exposure is important to prevent skin cancer, but careful monitoring of vitamin D status is recommended, with supplementation if hypovitaminosis D is detected.

Adherencia al tratamiento tras trasplante renal como indicador de calidad de la información recibida: estudio longitudinal con un seguimiento de 2 años / Adherence to treatment after kidney transplantation as quality indicator of the information received: longitudinal study of 2 years follow-up

Introducción. El trasplante es una modalidad de tratamiento óptima para la enfermedad renal crónica avanzada, que requiere de por vida la adherencia al tratamiento inmunosupresor. El objetivo de este estudio fue evaluar la adherencia al tratamiento después de un trasplante renal. Además de analizar el grado de información recibida al mes y 18 meses postrasplante y valorar su influencia en la adherencia al tratamiento. Material y métodos. El Cuestionario simplicado de adherencia a la medicación fue administrado al mes (T1), 6 meses (T2), 12 meses (T3), 18 meses (T4) y 24 meses (T5) postrasplante. La encuesta sobre aspectos del conocimiento y actitudes con respecto a la medicación se utilizó al mes y 18 meses postrasplante. Los datos se presentaron con medidas de tendencia central, y fueron comparados con pruebas no paramétricas. Resultados. Participaron 73 pacientes, con una mediana de edad de 57 años. El porcentaje de pacientes no-adherentes a la medicación fueron el 9,6% (T1), 22,5% (T2), 29,2% (T3), 29,8% (T4) y 28,1% (T5). Al mes del trasplante «no consultar con el médico al olvidarse alguna toma» (p=0,034) influyó significativamente en la no-adherencia farmacológica. A los 18 meses postrasplante ninguna de las cuestiones planteadas sobre el conocimiento de la medicación influyó en la no-adherencia al tratamiento farmacológico. Conclusiones. El mayor tiempo desde el trasplante incrementó la no-adherencia al tratamiento. Algunas cuestiones referidas a la información dada sobre el tratamiento influyeron en la no-adherencia en el trasplante inmediato, pero no en el seguimiento (AU)

Introduction. Transplantation is an optimal form of treatment for end-stage renal disease, but requires lifelong adherence to immunosuppressive therapy. The aim of this study was to longitudinally assess the adherence to treatment after kidney transplant, as well as to compare the amount of information about the treatment received at one month and 18 months post-transplantation, and its influence on adherence to treatment. Material and methods. The Self-Reported Measure of Medication Adherence was administered at month (T1), 6 months (T2), 12 months (T3), 18 months (T4), and 24 months (T5) post-transplantation. Survey about aspects of knowledge and attitudes about medication, was administered at one month and 18 months post-transplant. Measures of central tendency and non-parametric tests were used to compare the data. Results. The study included a total of 73 patients with a median age of 57 years. The percentage of patients non-adherent to medication was 9.6% (T1), 22.5% (T2), 29.2% (T3), 29.8% (T4), and 28.1% (T5). One month after transplantation “not consulting with the doctor on forgetting to take medication (P=.034) significantly influenced the non-adherence to treatment. At 18 months post- transplantation, none of the issues raised on medication knowledge had an influence on non-adherence to treatment. Conclusions. Longer times since transplantation increased the non-adherence to treatment. Some issues regarding the information of treatment influenced the non-adherence in the immediate transplant period, but not in the follow-up (AU)

[Adherence to treatment after kidney transplantation as quality indicator of the information received: Longitudinal study of 2 years follow-up]. / Adherencia al tratamiento tras trasplante renal como indicador de calidad de la información recibida: estudio longitudinal con un seguimiento de 2 años.

INTRODUCTION: Transplantation is an optimal form of treatment for end-stage renal disease, but requires lifelong adherence to immunosuppressive therapy. The aim of this study was to longitudinally assess the adherence to treatment after kidney transplant, as well as to compare the amount of information about the treatment received at one month and 18 months post-transplantation, and its influence on adherence to treatment. MATERIAL AND METHODS: The Self-Reported Measure of Medication Adherence was administered at month (T1), 6 months (T2), 12 months (T3), 18 months (T4), and 24 months (T5) post-transplantation. Survey about aspects of knowledge and attitudes about medication, was administered at one month and 18 months post-transplant. Measures of central tendency and non-parametric tests were used to compare the data. RESULTS: The study included a total of 73 patients with a median age of 57 years. The percentage of patients non-adherent to medication was 9.6% (T1), 22.5% (T2), 29.2% (T3), 29.8% (T4), and 28.1% (T5). One month after transplantation "not consulting with the doctor on forgetting to take medication (P=.034) significantly influenced the non-adherence to treatment. At 18 months post- transplantation, none of the issues raised on medication knowledge had an influence on non-adherence to treatment. CONCLUSIONS: Longer times since transplantation increased the non-adherence to treatment. Some issues regarding the information of treatment influenced the non-adherence in the immediate transplant period, but not in the follow-up.

Ureteropielostomía con vía nativa en el tratamiento de la uropatía obstructiva en el trasplante renal adulto. Experiencia y posibilidades técnicas / Native ureteropyelostomy in the treatment of obstructive uropathy in adult renal transplant. Experience and technical alternatives

Objetivo: Analizar y evaluar nuestra experiencia en el tratamiento quirúrgico mediante abordaje abierto de las estenosis ureterales complejas postrasplante renal de adulto en un centro de tercer nivel en los últimos 7 años. Se revisan las diferentes alternativas quirúrgicas utilizadas. Pacientes y métodos: Desde enero de 2005 hasta diciembre de 2012 se han realizado un total de 589 trasplantes renales de adulto consecutivos. Un 1,1% del total presentaron algún grado de uropatía obstructiva sintomática que, tras derivación urinaria inicial, requirieron de abordaje quirúrgico abierto utilizando la vía urinaria nativa ipsilateral o contralateral. Se presentan las características de los pacientes, clínica, exploraciones realizadas así como técnica quirúrgica llevada a cabo y sus resultados. Resultados: Durante el periodo evaluado se llevaron a cabo un total de 7 cirugías reparativas en 5 varones y 2 mujeres que presentaban estenosis ureterales postrasplante renal mediante ureteropielostomía abierta utilizando uréter nativo ipsilateral en 6 casos y contralateral en el restante. En un caso de realizó anastomosis ureterocalicilar por retracción piélica extrema. No ha habido complicaciones relevantes ni se ha requerido de nefrectomía de riñón nativo por complicación posterior. La totalidad de los pacientes intervenidos presentaron cifras de creatinina plasmática óptimas con resolución de la dilatación previa. Conclusiones: La nefrostomía percutánea inicial seguida de la corrección quirúrgica abierta mediante la utilización de uréter nativo representa una alternativa definitiva, válida y óptima en términos de seguridad y preservación de la función renal

Objective: To analyze and evaluate our experience in surgical treatment with the open approach of the complex ureteral stenosis after adult kidney transplantation in a tertiary level hospital in the last seven years. We have reviewed the different surgical options used. Patients and methods: A total of 589 consecutive adult renal transplants were performed from January 2005 to December 2012. Of these, 1.1% showed some degree of symptomatic obstructive uropathy which after initial urinary diversion required open surgical approach using the ipsilateral or contralateral native urinary tract. Characteristics of the patient, clinical examinations performed and surgical technique performed as well as their results are presented. Results: During the period under review, in 5 men and 2 women who had ureteral stenoses after renal transplant, 7 reparative surgeries were performed by open ureteropyelostomy, using ipsilateral native ureter in 6 cases and contralateral ureter in the remaining case. In one case, uretero-calicial anastomosis was performed due to severe pyelic shrinkage. There were no significant complications. Native kidney nephrectomy was not required for further complications. All the patients operated on had optimum plasma creatinine levels with resolution of previous dilatation. Conclusions: The initial percutaneous nephrostomy followed by open surgical repair using native ureter represents a definitive, valid and optimal alternative in terms of safety and preservation of renal function

Low serum mannose-binding lectin levels are associated with inflammation and apoptosis in early surveillance allograft biopsies.

INTRODUCTION: Mannose-binding lectin (MBL) is a protein of the innate immune system that participates in host defense and the tissue injury/repair process, enhancing the clearance of apoptotic cells by macrophages. The aim is to characterize the relationship between pre-transplant MBL levels, histological lesions and number of apoptotic cells in early surveillance renal allograft biopsies. PATIENTS AND METHODS: Consecutive renal transplant recipients were recruited and MBL levels were classified into tertiles. The first tertile was considered the low MBL group. Surveillance biopsies were done during the first 6 months and were evaluated according to Banff criteria. Renal inflammatory infiltrates were studied by immunohistochemical techniques. Apoptosis was studied using morphological methods in renal tubular cells and was expressed as the number of apoptotic cells/mm(2). RESULTS: MBL was determined in 126 patients and a surveillance biopsy with sufficient tissue was obtained in 41 of them. Patients with low pre-transplant MBL levels showed a higher acute Banff index (3.14 ± 1.96 vs. 1.88 ± 1.56, p = 0.044) and an increased proportion of biopsies with tubular cell apoptosis The proportion of biopsies with tubular cell apoptosis was higher in patients with low pre-transplant MBL levels in comparison with patients with high MBL levels (4.3 ± 3.6 versus 0.2 ± 0.9 p = 0.012) and increased interstitial number of inflammatory cells and significantly the macrophages/mm(2) (109 ± 118 vs. 32 ± 46; p = 0.04). CONCLUSION: Low pre-transplant serum MBL levels are associated with more severe inflammation and increased apoptosis in early surveillance renal allograft biopsies suggesting that MBL modulates renal inflammation after transplantation.

Native ureteropyelostomy in the treatment of obstructive uropathy in adult renal transplant. Experience and technical alternatives.

OBJECTIVE: To analyze and evaluate our experience in surgical treatment with the open approach of the complex ureteral stenosis after adult kidney transplantation in a tertiary level hospital in the last seven years. We have reviewed the different surgical options used. PATIENTS AND METHODS: A total of 589 consecutive adult renal transplants were performed from January 2005 to December 2012. Of these, 1.1% showed some degree of symptomatic obstructive uropathy which after initial urinary diversion required open surgical approach using the ipsilateral or contralateral native urinary tract. Characteristics of the patient, clinical examinations performed and surgical technique performed as well as their results are presented. RESULTS: During the period under review, in 5 men and 2 women who had ureteral stenoses after renal transplant, 7 reparative surgeries were performed by open ureteropyelostomy, using ipsilateral native ureter in 6 cases and contralateral ureter in the remaining case. In one case, uretero-calicial anastomosis was performed due to severe pyelic shrinkage. There were no significant complications. Native kidney nephrectomy was not required for further complications. All the patients operated on had optimum plasma creatinine levels with resolution of previous dilatation. CONCLUSIONS: The initial percutaneous nephrostomy followed by open surgical repair using native ureter represents a definitive, valid and optimal alternative in terms of safety and preservation of renal function.

Contribution of anemia and hypertension to left ventricular hypertrophy during the initial 2 years after renal transplantation.

BACKGROUND: Cardiovascular disease is the main cause of mortality after renal transplantation. Left ventricular hypertrophy (LVH) is considered to be an independent predictor of cardiovascular events. The main risk factors for LVH after renal transplantation are anemia and hypertension. In hypertensive and renal transplant patients, ambulatory blood pressure monitoring (ABPM) has been demonstrated to be more closely related to LVH than office blood pressure. The aim of this study has to evaluate LVH after renal transplantation, particularly its association with measures derived from ABPM and cardiovascular risk factors. PATIENTS AND METHODS: Between March 2005 and October 2006, we recruited 101 consecutive kidney transplant patients to calculate left ventricular mass index (LVMI) by echocardiography at 3, 12, and 24 months. Hypertension was evaluated by office blood pressure measurements at 3, 12, and 24 months and also by ABPM at 3 months. Clinical and laboratory data were recorded during the study. RESULTS: From 3 to 24 months LVMI was reduced from 129 ± 29 g/m(2) to 121 ± 34 g/m(2) (P = .0089). Multivariate stepwise regression analysis showed independent predictors of LVMI at 3 months to be hemoglobin at 1 month, day systolic blood pressure (SBP) derived from ABPM and donor age (R = .50, P < .001). The independent predictors of LVMI at 12 months were day SBP derived from ABPM, hemoglobin at 1 month, and proteinuria at 12 months (R = .55, P < .001). Office SBP at 12 months, proteinuria at 24 months, patient age and night diastolic blood pressure derived from ABPM at 3 months were independent predictors of LVMI at 24 months (R = .71, P < .001). CONCLUSION: We observed a significant reduction in LVMI after renal transplantation. The main contributors to LVMI were anemia and elevated blood pressures measured by ABPM.

Histological findings in two renal transplants accomplishing operational tolerance criteria.

Operational tolerance is defined as stable renal function in transplants without immunosuppression for at least 1 year. We present histological assessments of two patients with operational tolerance. The first withdrew immunosuppression in 2005 and presents stable renal function (creatinine 1.5 mg/dL) without proteinuria. The biopsy showed mild chronic tubulointerstitial changes without inflammation. The second withdrew immunosuppression in 2009 and maintains stable renal function (creatinine 1.6 mg/dL) with mild proteinuria. Histology showed chronic humoural rejection and Class II anti-human leukocyte antigen antibodies were detected. These cases suggest that a renal biopsy may be useful to rule out subclinical pathology in patients with operational tolerance.

Diabetes mellitus postrasplante según técnica de diálisis previa al trasplante / No disponible

La diabetes mellitus postrasplante (DMPT) es una de las complicaciones más importantes del paciente trasplantado renal, pues tiene importantes repercusiones sobre la supervivencia del injerto y del paciente. El diagnóstico de DMPT debe realizarse según los criterios de la American Diabetic Association. Estudios recientes demuestran la utilidad de realizar un test de tolerancia oral a la glucosa a todos los pacientes. Son muchos los factores de riesgo que favorecen la DMPT. Controlando los factores modificables (inmunosupresión, obesidad, infecciones…) se puede reducirla incidencia de DMPT. Según los datos del RMRC los pacientes en diálisis peritoneal son más jóvenes, pero presentan un mayor porcentaje de dislipemia y obesidad. Datos recientes sugieren que la inflamación subclínica, la adiponectina y la ghrelina pueden ser un importante factor patogénico en el desarrollo de la resistencia a la insulina y la diabetes mellitus. No existen evidencias claras de que la técnica de diálisis influya en el estado inflamatorio subclínico y las adipocitoquinas. Según datos del grupo español de estudio de la DMPT existe relación entre las concentraciones de ghrelina y el sexo en los pacientes de diálisis peritoneal. La complicación metabólica más frecuente de los pacientes en diálisis peritoneal es la hiperglicemia. La hiperglicemia pretrasplante favorece la aparición de DMPT. No existen evidencias claras en la literatura que demuestren que la técnica de diálisis sea un factor de riesgo para la aparición de DMPT. Son necesarios más estudios multicéntricos que analicen las características clínicas y biológicas del paciente renal y su relación con la DMPT (AU)

Post-transplant diabetes mellitus (PTDM) is one of the most important complications in kidney transplant patients because it has a significant impact on graft and patient survival. Diagnosis of PTDM should be based on the American Diabetic Association criteria. Recent studies show the value of performing an oral glucose tolerance test in all patients. Multiple risk factors promote PTDM. PTDM incidence may be reduced by controlling modifiable factors (immune suppression, obesity, infections…). According to RMRC data, patients on peritoneal dialysis are younger, but have a greater incidence rate of dyslipidemia and obesity. Recent data suggest that subclinical information, adiponectin, and ghrelin may be a significant pathogenetic factor in development of insulin resistance and diabetes mellitus. There is no clear evidence that the dialysis procedure influences the subclinical inflammatory state and adipocytokines. According to data from the Spanish group for the study of PTDM, a relationship exists between ghrelin levels and sex in patients on peritoneal dialysis. The most common metabolic complication in patients on peritoneal dialysis is hyperglycemia. Pre-transplant hyperglycemia promotes the occurrence of PTDM. There is no clear evidence in the literature showing that the dialysis procedure is a risk factor for the occurrence of PTDM. Additional multicenter studies are required to analyze the clinical and biological characteristics of renal patients and their relationship to PTDM (AU)

[Post-transplant diabetes mellitus depending on the pre-transplant dialysis technique]. / Diabetes mellitus post-trasplante según técnica de diálisis previa al trasplante.

Post-transplant diabetes mellitus (PTDM) is one of the most important complications in kidney transplant patients because it has a significant impact on graft and patient survival. Diagnosis of PTDM should be based on the American Diabetic Association criteria. Recent studies show the value of performing an oral glucose tolerance test in all patients. Multiple risk factors promote PTDM. PTDM incidence may be reduced by controlling modifiable factors (immunosuppression, obesity, infections...). According to RMRC data, patients on peritoneal dialysis are younger, but have a greater incidence rate of dyslipidemia and obesity. Recent data suggest that subclinical information, adiponectin, and ghrelin may be a significant pathogenetic factor in development of insulin resistance and diabetes mellitus. There is no clear evidence that the dialysis procedure influences the subclinical inflammatory state and adipocytokines. According to data from the Spanish group for the study of PTDM, a relationship exists between ghrelin levels and sex in patients on peritoneal dialysis. The most common metabolic complication in patients on peritoneal dialysis is hyperglycemia. Pre-transplant hyperglycemia promotes the occurrence of PTDM. There is no clear evidence in the literature showing that the dialysis procedure is a risk factor for the occurrence of PTDM. Additional multicenter studies are required to analyze the clinical and biological characteristics of renal patients and their relationship to PTDM.

Cómo mejorar la hipotensión sintomática en hemodiálisis: diálisis fría vs diálisis isotérmica / How can we improve sythomatic hypotension in hemodiaysis patients: Cold dialysis Vs isothermic dialysis

Introducción: La hipotensión sintomática es la complicación aguda más frecuente que afecta a los pacientes durante las sesiones de hemodiálisis. Varios trabajos han demostrado que el uso de baja temperatura en el baño de diálisis protege de esta hipotensiónen pacientes susceptibles de ella. En nuestro estudio, analizamos si la prevención de la reacción hipertérmica de la sesión de hemodiálisis tendría una respuestafavorable en la estabilidad hemodinámica de los pacientes permitiéndoles una buena tolerancia.Métodos: Analizamos el efecto del control de temperatura del dializado en la estabilidad hemodinámica de pacientes predispuestos a hipotensión sintomática ennuestro centro. En la fase de screening seleccionamos aquellos pacientes que tuvieron más de tres episodios hipotensivos en las 12 sesiones del mes. Posteriormente los mismos pacientes pasaron a las siguientes dos fases de 4 semanas cada una. En la fase 1, ajustamos la temperatura del baño a 36º C de forma constante para las 12 sesiones (diálisis fría) y en la segunda fase, utilizamos un (Blood Temperature Monitor; FreseniusMedical Care, Bad Homberg, Germany), que permite mantener constante la temperatura corporal (diálisis isotérmica). Resultados: Nueve pacientes fueron incluidos yfinalizaron el estudio. Durante la fase de screening la sustracción media fue del 4 ± 1% del 16 mmHg ± 16 a 80 ± peso seco, disminuyendo la tensión arterial mediadesde 99 (p < 1,7 sesiones de 12 ± 0,001) y presentando hipotensión sintomática en 5,0. Tanto en la fase 1 como en la 2 observamos un descenso de los tratamientos 1,7 ±1,6 y 2,8 ± 1,7 versus 2,7 ± complicados con hipotensión sintomática (5,0 p < 0,01). Ambas técnicas: Diálisis fría tanto como diálisis isotérmica fueron bien toleradas por los pacientes. Conclusión: Los resultados muestran que un control activo de la temperatura corporal puede mejorar de forma significativa la tolerancia intradialítica en pacientespredispuestos a la hipotensión sintomática (AU)

Background: Symptomatic hypotension is the most frequent acute complication affecting patients during chronic hemodialysis treatment sessions. Many reports have demonstrated that the use of cool dialysate has a protective effect on blood pressure duringhemodialysis treatments. In the present study, we investigated whether preventing the hyperthermic response had favourable effects on hemodynamic stability during the hemodialysis procedure while affording good tolerance to patients.Methods:We investigated the effect of thermal control of dialysate on hemodynamic stability in hypotensionpronepatients in our center. Patients were eligible for the study if they had symptomatic hypotensive episodes (> 3/12 session/month) during the screening phase. The studywas designed with two phases for the same selected patients and two treatment arms, each phase lasting 4 weeks. In the first phase, we adjusted dialysate temperature on 36 ºC for 12 sessions (cold dialysis) and in the second phase we used a device allowing theregulation of thermal balance (Blood Temperature Monitor; Fresenius Medical Care, Bad Homberg, Germany), that keep body temperature unchanged (isothermic dialysis). Results: Nine HD patients were enrolled and completed the study. During the screening 1% of dry weight, and blood pressure ± phase the mean ultrafiltration was 4 16 mmHg (p ± 16 to 80 ± decreased from 99 < 1.7 sessions of 12 ± 0.001). In 5.0 treatments were complicated by hypotension. In the first and second phase we observed a decrease of complicated treatments with symptomatic hypotension 1.7; p ± 1.6 y 2.8 ± 1.7 versus 2.7 ± (5.0 < 0.01). Both procedures: Cold dialysis and Isothermic dialysis was well tolerated by patients. Conclusion: Results show that active control of body temperature can significantly improve intradialytic tolerance in hypotension-prone patients (AU)

Immunephenotype of glomerular and interstitial infiltrating cells in protocol renal allograft biopsies and histological diagnosis.

Patients with a protocol renal allograft biopsy simultaneously displaying interstitial fibrosis/tubular atrophy (IF/TA) and subclinical rejection (SCR) have a shortened graft survival than patients with a normal biopsy, or with a biopsy only displaying IF/TA or SCR. The poor outcome of these patients could be related with a more severe inflammation. We evaluate the immunophenotype of infiltrating cells in these diagnostic categories. Nonexhausted paraffin blocks from protocol biopsies done during the first year were stained with anti-CD45, CD3, CD20, CD68 and CD15 monoclonal antibodies. Glomerular and interstitial positive cells were counted. C4d deposition in peritubular capillaries was evaluated. Histological diagnoses were: normal (n = 80), SCR (n = 17), IF/TA (n = 42) and IF/TA + SCR (n = 17). Only interstitial CD20 positive cells were significantly increased in patients displaying IF/TA + SCR; normal (137 +/- 117), SCR (202 +/- 145), IF/TA (208 +/- 151) and IF/TA + SCR (307 +/- 180 cells/mm(2)), p < 0.01. The proportion of biopsies displaying C4d deposition was not different among groups. The upper tertile of CD20 positive interstitial cells was associated with a decreased death-censored graft survival (relative risk: 3.01, 95% confidence interval: 1.23-7.35; p = 0.015). These data suggest that B-cell interstitial infiltrates are associated with histological damage and outcome, but do not distinguish whether these infiltrates were the cause or the consequence of chronic tubulo-interstitial damage.

Donor structural and functional parameters are independent predictors of renal function at 3 months.

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% = 0, >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 < .01) and donor chronic damage score (R = 0.32, P < .01). GFR was lower among recipients of female versus male donors (50 +/- 15 vs 60 +/- 20 mL/min; P < .01). Donor cerebrovascular accident death (53 +/- 19 vs 63 +/- 19 mL/min; P < .01) and hypertension (48 +/- 16 vs 59 +/- 20 mL/min; P < .01) were also associated with lower GFR at 3 months. There was a positive correlation between GFR at admission, GFR preprocurement, and GFR at 3 months (R = 0.32 and R = 0.18 respectively; P < .01). Stepwise regression analysis included chronic damage score, GFR at admission, and donor gender but not donor age as independent predictors of GFR at 3 months (R = 0.50; P < .01). CONCLUSION: Donor structural and functional parameters are independent predictors of renal function at 3 months.

Poly(ADP-ribose) polymerase expression in kidney transplantation: from alfa (alpha) to Omega (Omega).

INTRODUCTION: Overactivation of the enzyme poly(ADP-ribose) polymerase (PARP-1) can be induced by ischemia-reperfusion and involved in the renal injury subsequent to kidney transplant. The poly(ADP-ribosy)lation mechanism alters free radical-induced DNA damage, which is repair by PARP-1 polymer. However, PARP-1 overexpression induces cellular necrosis. Our aim was to study the immunohistochemical PARP-1 expression in kidney transplant biopsies associated with various events. MATERIALS AND METHODS: We studied the nuclear expression of PARP-1 in kidney tubule cells by immunohistochemistry using the monoclonal antibody PAR01 in donor biopsies without acute tubular necrosis (ATN) (n = 60; controls), allografts that suffer ATN (n = 90) or an episode of acute humoral rejection (n = 12) or acute tubulointerstitial rejection (n = 25), or chronic allograft nephropathy (n = 25). Furthermore, we also studied protocol biopsies with subclinical rejection (n = 60). Renal lesions in transplant biopsies were graded blindly using 1997 Banff criteria without any clinical information. RESULTS: Biopsies without morphological features of ATN, namely acute tubulointerstitial rejection, borderline or subclinical rejection, showed lesser PARP-1 expression compared with biopsies with ATN or with ischemic mechanism of acute humoral rejection or chronic allograft nephropathys. We observed an inverse relation between PARP-1 expression and renal function (P < .001). Overall, renal biopsies showing ATN revealed greater expression of PARP-1 (r = 0.785, Pearson test). A significant relationship with PARP-1 expression was demonstrated with renal function (effective diuresis, serum creatinine levels) and pretransplant cold ischemia time (P < .001). CONCLUSION: Kidney transplant events including ischemia were associated with the highest PARP-1 expression and worse allograft renal function.

Pharmacokinetics and pharmacodynamics in renal transplant recipients under treatment with cyclosporine and Myfortic.

INTRODUCTION: Efficacious prophylaxis of acute rejection episodes (ARE) requires adequate exposure to each component of the immunosuppressive treatment from the first days after renal transplantation. The aim of the present study was to evaluate the correlation between cyclosporine (CsA) and mycophenolic acid (MPA) exposure based upon pharmacokinetics (PK) and pharmacodynamics (PD) and 6-month biopsy-proven acute rejection (BPAR) episodes and chronic allograft nephropathy on 6 month protocol biopsies. PATIENTS AND METHODS: We examined twenty-two first or second de novo renal transplant recipients treated with steroids, Sandimmune Neoral (CsA) and Myfortic (720 mg twice a day). PK (C0, C2, and AUC(0-12h)) for both drugs were determined on days 7, 90, and 180. Calcineurin activity, interleukin-2 and interferon-gamma synthesis as well as %CEM were tested at days 7 and 180. CsA dosages were adjusted by C2 monitoring. Collected data included: BPAR during the first 6 months and Banff histological parameters on the 6-month protocol biopsies. RESULTS: Eighteen of 22 patients completed 1 year follow-up under treatment. The 6-month BPAR was 18% (4/22). Six-month protocol biopsies in 50% of 14 recipients showed chronic allograft nephropathy 1. At day 7, CsA C2 and AUC median values were 138 ng/mL and 6377 ng x h/mL, while C0 MPA was 1.0 microg/mL and AUC = 23.9 microg x h/mL. CsA C2 medians at 3 and 6 months were 1468 and 1720 ng/mL. MPA-AUC reached therapeutic targets at 3 months (32.3 microg x h/mL) and was 48.3 microg x h/mL at 6 months. Patients with BPAR showed lower CsA AUC (P = .06) and a significantly lower baseline inhibition of calcineurin activity (P < .005) than patients with no BPAR. An increase in mesangial matrix in 6-month protocol biopsies correlated with higher CsA C2 (P = .01). All biomarkers evaluated were significantly inhibited compared with the standard population. CONCLUSIONS: When Myfortic is administered together with CsA, it is advisable to begin with higher doses (720 mg x 3 days) to reach adequate PK targets and improve BPAR rates. To prevent chronic allograft nephropathy, lower CsA C2 should be targeted from 3 months.

Protocol biopsies in renal transplantation: prognostic value of structural monitoring.

The natural history of renal allograft damage has been characterized in serial protocol biopsies. The prevalence of subclinical rejection (SCR) is maximal during the first months and it is associated with the progression of interstitial fibrosis/tubular atrophy (IF/TA) and a decreased graft survival. IF/TA rapidly progress during the first months and constitutes an independent predictor of graft survival. IF/TA associated with transplant vasculopathy, SCR, or transplant glomerulopathy implies a poorer prognosis than IF/TA without additional lesions. These observations suggest that protocol biopsies could be considered a surrogate of graft survival. Preliminary data suggest that the predictive value of protocol biopsies is not inferior to acute rejection or renal function. Additionally, protocol biopsies have been employed as a secondary efficacy variable in clinical trials. This strategy has been useful to demonstrate a decrease in the progression of IF/TA in some calcineurin-free regimens. Quantification of renal damage is associated with graft survival suggesting that quantitative parameters might improve the predictive value of protocol biopsies. Validation of protocol biopsies as a surrogate of graft survival is actively pursued, as the utility of classical surrogates of graft outcome such as acute rejection has become less useful because of its decreased prevalence with actual immunosuppression.

Immunosuppression for dual kidney transplantation with marginal organs: the old is better yet.

Immunosuppressive protocols in dual kidney transplantation (DKT) are based on calcineurin 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.

[How can we improve symptomatic hypotension in hemodialysis patients: cold dialysis vs isothermic dialysis]. / Cómo mejorar la hipotensión sintomática en hemodiálisis: diálisis fría versus diálisis isotérmica.

BACKGROUND: Symptomatic hypotension is the most frequent acute complication affecting patients during chronic hemodialysis treatment sessions. Many reports have demonstrated that the use of cool dialysate has a protective effect on blood pressure during hemodialysis treatments. In the present study, we investigated whether preventing the hyperthermic response had favourable effects on hemodynamic stability during the hemodialysis procedure while affording good tolerance to patients. METHODS: We investigated the effect of thermal control of dialysate on hemodynamic stability in hypotension-prone patients in our center. Patients were eligible for the study if they had symptomatic hypotensive episodes (> 3/12session/ month) during the screening phase. The study was designed with two phases for the same selected patients and two treatment arms, each phase lasting 4 weeks. In the first phase, we adjusted dialysate temperature on 36 masculineC for 12 sessions (cold dialysis) and in the second phase we used a device allowing the regulation of thermal balance (Blood Temperature Monitor; Fresenius Medical Care, Bad Homberg, Germany), that keep body temperature unchanged (isothermic dialysis). RESULTS: Nine HD patients were enrolled and completed the study. During the screening phase the mean ultrafiltration was 4 1% of dry weight, and blood pressure decreased from 9916 to 8016 mm Hg (p<0.001). In 5.01.7 sessions of 12 treatments were complicated by hypotension. In the first and second phase we observed a decrease of complicated treatments with symptomatic hypotension (5.01.7 versus 2.71.6 y 2.81.7; p<0.01). Both procedures: Cold dialysis and Isothermic dialysis was well tolerated by patients. CONCLUSION: Results show that active control of body temperature can significantly improve intradialytic tolerance in hypotension-prone patients.