Body Fat Distribution, Adipocytokines Levels and Variability in Associated Genes and Kidney Transplant Outcomes.

Introduction: Body fat distribution is known to contribute to a variety of pathologies. Research Questions: We aimed to assess whether this distribution is associated with clinical outcomes in renal transplant recipients (RTR) and to examine its relationship with leptin and adiponectin gene variants and plasma concentrations. Design: Bioelectrical impedance analyses were performed in 236 RTR. Leptin/adiponectin levels were measured by immunoassay and relevant polymorphisms in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes were identified. Associations were assessed by logistic regression modeling. Results: The waist-to-height ratio (WHr) displayed a significant association with delayed graft function, acute rejection and post-transplant diabetes mellitus, with OR values of 2.04 (1.02-4.08) p = 0.045; 3.08 (1.22-7.79) p = 0.017 and 2.79 (1.16-6.74) p = 0.022, respectively. Waist circumference was linked to delayed graft function [OR = 1.03 (1.01-1.05), p = 0.025] and AR [OR = 1.041 (1.01-1.07), p = 0.009]. Leptin levels were significantly higher in patients who experienced rejection [19.91 ± 23.72 versus 11.22 ± 16.42 ng/ml; OR = 1.021 (1.01-1.04), p = 0.017]. The ADIPOQ rs1501299TT genotype showed a significant association with higher WHr (0.63 ± 0.11 vs 0.59 ± 0.87 for GG/GT genotypes; p = 0.015) and WC values (102.3 ± 14.12 vs 96.38 ± 14.65 for GG/GT genotypes; p = 0.021). Conclusion: WC, and especially WHr, are associated with adverse outcomes in renal transplantation and are affected by variability in the ADIPOQ gene.

Patterns of progression of chronic kidney disease at later stages.

BACKGROUND: At later stages of chronic kidney disease (CKD), a pattern of linear and irreversible renal function decline is thought to be the most common. The objective of this study was to describe the characteristics of the different patterns of CKD progression, and to investigate potentially modifiable factors associated with the rate of decline of renal function. METHODS: This was a retrospective, observational study in a cohort of adult patients with CKD Stage 4 or 5 not on dialysis. Decline in renal function was estimated as the slope of the individual linear regression line of estimated glomerular filtration rate (eGFR) over time. The following patterns of CKD progression were considered: unidentifiable, linear, nonlinear (curvilinear) and positive (improvement of renal function). RESULTS: The study group consisted of 915 patients (mean ±SD age 65 ± 14 years, 48% females, median follow-up time 16 months). A linear pattern was observed in 38%, unidentifiable in 23%, nonlinear in 24% and positive in 15% of the study patients. The mean eGFR slope was: -3.35 ± 4.45 mL/min/year. Linear and unidentifiable patterns were associated with more rapid loss of renal function. By multiple linear and logistic regression analysis, the magnitude of proteinuria, the systolic blood pressure and the treatment with dual renin-angiotensin system blockade were associated with more rapid CKD progression. On the contrary, older age and discontinuation of commonly prescribed medication with potential influence on renal function or eGFR measurements were associated with slower CKD progression. CONCLUSIONS: A majority of patients with advanced CKD show patterns of renal function decline different from linear, and several of the main determinants of CKD progression are potentially modifiable.

Cambios de la función renal tras la suspensión de análogos de vitamina D en la enfermedad renal crónica avanzada / Changes in renal function after discontinuation of vitamin D analogues in advanced chronic kidney disease

Antecedentes: En la práctica clínica habitual la prescripción de análogos de vitamina D (AVD) en la enfermedad renal crónica (ERC) se asocia con frecuencia a un descenso de la función renal estimada cuyo origen no es bien conocido. Objetivos: Analizar el efecto de la suspensión de un tratamiento previo con AVD en ERC avanzada, y determinar los factores asociados con los cambios de función renal. Material y métodos: Estudio de cohorte retrospectivo en pacientes adultos incidentes con ERC avanzada. El subgrupo caso estaba siendo tratado con AVD y esta medicación fue suspendida en la primera visita. El subgrupo control no había sido tratado con AVD y fueron elegidos por criterios de coincidencia para datos relevantes relacionados con la progresión de la ERC. La variable de resultado principal fue el cambio de filtrado glomerular, tanto el estimado (FG-MDRD) como el medido (media del aclaramiento de creatinina y urea), con respecto al siguiente control analítico. Parámetros basales relacionados con el metabolismo mineral y la generación de creatinina fueron analizados como determinantes potenciales de los cambios de la función renal. Resultados: Se incluyeron 67 pacientes casos y otros 67 controles. El 67% de los casos mejoró la función renal, mientras que el 72% de los controles empeoró (p<0,0001). El cambio FG-MDRD en casos y controles fue +0,455±0,997 vs. −0,436±1,103ml/min/1,73 m2/mes (p<0,0001), respectivamente. La excreción total de creatinina era ligeramente superior en los casos, pero la diferencia con respecto a los controles no fue significativa. Por regresión logística y lineal multivariante, el calcio sérico total basal fue uno de los principales determinantes tanto de la recuperación de la función renal (odds ratio=3,49; p=0,001), como de la magnitud de esta recuperación (beta=0,276; p=0,001). Conclusiones: La suspensión de AVD en pacientes con ERC se asocia con una mejoría significativa de la función renal estimada. La magnitud de estos cambios se relaciona principalmente con la calcemia basal (AU)

Background: In routine clinical practice, the prescription of vitamin D analogues (VDA) in patients with chronic kidney disease (CKD) is often associated with a decline of the estimated renal function. The reason for this is not fully understood. Aims: To analyse the effects of VDA discontinuation in advanced CKD and to determine the factors associated with changes in renal function. Material and methods: Retrospective cohort study of adult patients with advanced CKD. The case subgroup was treated with VDA and this medication was discontinued at baseline (the first visit). The control subgroup was not treated with VDA and they were selected according to comparability principles for CKD progression by propensity score matching. The primary outcome measure was a change to both the estimated glomerular filtration rate (MDRD-GFR) and the measured glomerular filtration rate (mGFR by combined creatinine and urea clearances). Baseline parameters related to mineral metabolism and creatinine generation were analysed as potential determinants of renal function changes. Results: The study sample consisted of 67 cases and 67 controls. Renal function improved in 67% of cases and worsened in 72% of controls (p<0.0001). Changes in MDRD-GFR for the case subgroup and the control subgroup were +0.455±0.997 vs. −0.436±1.103ml/min/1.73 m2/month (p<0.0001), respectively. Total creatinine excretion was slightly higher in cases than in controls but the difference was not significant. According to multivariate logistic and linear regression analyses, baseline total serum calcium was one of the best determinants of both renal function recovery (Odds ratio=3.49; p=0.001), and of the extent of renal function recovery (beta=0.276; p=0.001). Conclusions: Discontinuation of VDA treatment in CKD patients is associated with significant recovery of estimated renal function. The extent of these changes is mainly associated with baseline total serum calcium (AU)

Polymorphisms in genes involved in vasoactive eicosanoid synthesis affect cardiovascular risk in renal transplant recipients.

OBJECTIVE: Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases leads to epoxyeicosatrienoic acids (EETs), which are eicosanoids with vasodilator and anti-inflammatory properties. We aim to determine whether genetic variability in these routes may contribute to cardiovascular (CV) risk in renal transplant recipients. METHODS: In a cohort of 355 patients, we determined the presence of two polymorphisms, CYP2C8*3 and CYP2J2*7, known to affect eicosanoid levels. Associations with CV mortality, CV event-free long-term survival and graft survival were retrospectively investigated by logistic regression models. RESULTS: CYP2J2*7 showed a statistical trend towards higher CV mortality (p = .06) and lower cardiac or cerebral event-free long-term survival (p = .05), whilst CYP2C8*3 displayed a significant inverse association with the risk of CV event (hazard ratio [HR] = 0.34 [0.15-0.78], p = .01). The association of CYP2J2*7 with CV mortality became significant when the analysis was restrained to 316 patients without a history of CV events prior to transplantation (HR = 15.72 [2.83-91.94], p = .005). In this subgroup of patients both single nucleotide polymorphisms (SNPs) were significantly associated with event-free survival. HR values were 5.44 (1.60-18.51), p = .007 and 0.26 (0.09-0.75), p = .012 for CYP2J2*7 and CYP2C8*3, respectively. CONCLUSIONS: Our results show, for the first time to our knowledge, that two SNPs in CYP2C8 and CYP2J2, which synthesize EETs, may modify CV outcomes in renal transplant recipients, a population that is already at a high risk of suffering these events.

Changes in renal function after discontinuation of vitamin D analogues in advanced chronic kidney disease. / Cambios de la función renal tras la suspensión de análogos de vitamina D en la enfermedad renal crónica avanzada.

BACKGROUND: In routine clinical practice, the prescription of vitamin D analogues (VDA) in patients with chronic kidney disease (CKD) is often associated with a decline of the estimated renal function. The reason for this is not fully understood. AIMS: To analyse the effects of VDA discontinuation in advanced CKD and to determine the factors associated with changes in renal function. MATERIAL AND METHODS: Retrospective cohort study of adult patients with advanced CKD. The case subgroup was treated with VDA and this medication was discontinued at baseline (the first visit). The control subgroup was not treated with VDA and they were selected according to comparability principles for CKD progression by propensity score matching. The primary outcome measure was a change to both the estimated glomerular filtration rate (MDRD-GFR) and the measured glomerular filtration rate (mGFR by combined creatinine and urea clearances). Baseline parameters related to mineral metabolism and creatinine generation were analysed as potential determinants of renal function changes. RESULTS: The study sample consisted of 67 cases and 67 controls. Renal function improved in 67% of cases and worsened in 72% of controls (p<0.0001). Changes in MDRD-GFR for the case subgroup and the control subgroup were +0.455±0.997 vs. -0.436±1.103ml/min/1.73 m2/month (p<0.0001), respectively. Total creatinine excretion was slightly higher in cases than in controls but the difference was not significant. According to multivariate logistic and linear regression analyses, baseline total serum calcium was one of the best determinants of both renal function recovery (Odds ratio=3.49; p=0.001), and of the extent of renal function recovery (beta=0.276; p=0.001). CONCLUSIONS: Discontinuation of VDA treatment in CKD patients is associated with significant recovery of estimated renal function. The extent of these changes is mainly associated with baseline total serum calcium.

Afectación glomerular en paciente con enfermedad falciforme / Glomerular involvement in patient with sickle cell disease

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High levels of both serum gamma-glutamyl transferase and alkaline phosphatase are independent preictors of mortality in patients with stage 4-5 chronic kidney disease. / Niveles séricos elevados de gamma-glutamil transferasa y fosfatasa alcalina son predictores independientes de mortalidad en la enfermedad renal crónica estadio 4-5.

INTRODUCTION: High serum gamma-glutamyl transferase (GGT) levels are associated with increased mortality in the general population. However, this association has scarcely been investigated in patients with chronic kidney disease (CKD). This study aims to investigate the clinical characteristics of CKD patients with abnormally elevated serum GGT, and its value for predicting mortality. MATERIAL AND METHODS: Retrospective observational study in a population cohort of adults with stage 4-5 CKD not yet on dialysis. Demographic, clinical, and biochemical parameters of prognostic interest were recorded and used to characterise CKD patients with high levels of GGT (>36 IU/l). Cox proportional hazard regression models were used to analyse the influence of baseline serum GGT and alkaline phosphatase (ALP) levels on mortality for whatever reason. RESULTS: The study group consisted of 909 patients (mean age 65±15 years). Abnormally elevated GGT or ALP levels at baseline were observed in 209 (23%) and 172 (19%) patients, respectively, and concomitant elevations of GGT and ALP in 68 (7%). High GGT levels were associated with higher comorbidity burden, and a biochemical profile characterised by higher serum concentration of uric acid, triglycerides, alanine aminotransferase, ferritin, and C-reactive. During the study period, 365 patients (40%) died (median survival time=74 months). In adjusted Cox regression models, high levels of GGT (hazard ratio [HR]=1.39;CI 95%: 1.09-1.78, P=.009) and ALP (HR=1.31; CI95%: 1.02-1.68, P=.038) were independently associated with mortality. CONCLUSION: High serum levels of GGT are independent predictors of mortality in CKD patients.

How to assess the efficacy of phosphate binders. / Cómo estimar la eficacia de un captor del fósforo.

BACKGROUND AND AIMS: The efficacy of phosphate binders is difficult to be estimated clinically. This study analyzes the changes in serum phosphate and urinary phosphate excretion after the prescription of phosphate binders (PB) in patients with chronic kidney disease stage 4-5 pre-dialysis, and the usefulness of the ratio between total urinary phosphate and protein catabolic rate (Pu/PCR) for estimating the efficacy of PB. METHODS: This retrospective observational cohort study included adult chronic kidney disease patients. Biochemical parameters were determined baseline and after 45-60 days on a low phosphate diet plus PB ("binder" subgroup=260 patients) or only with dietary advice ("control" subgroup=79 patients). RESULTS: Phosphate load (total urinary excretion) per unit of renal function (Pu/GFR) was the best parameter correlated with serum phosphate levels (R2=0.61). Mean±SD level of Pu/PCR was 8.2±2.3mg of urinary phosphate per each g of estimated protein intake. After treatment with PB, serum phosphate levels decreased by 11%, urinary phosphate 22%, protein catabolic rate 7%, and Pu/PCR 15%. In the control subgroup, Pu/PCR increased by 20%. Urinary phosphate and urea nitrogen excretion correlated strongly, both baseline and after PB or dietary advice. CONCLUSIONS: The proposed parameter Pu/PCR may reflect the rate of intestinal phosphate absorption, and therefore, its variations after PB prescription may be a useful tool for estimating the pharmacological efficacy of these drugs.

Niveles séricos elevados de gamma-glutamil transferasa y fosfatasa alcalina son predictores independientes de mortalidad en la enfermedad renal crónica estadio 4-5 / High levels of both serum gamma-glutamyl transferase and alkaline phosphatase are independent preictors of mortality in patients with stage 4-5 chronic kidney disease

Introducción: Los niveles séricos elevados de gamma-glutamil transferasa (GGT) se asocian con una mayor mortalidad en la población general, pero es desconocido si esta asociación también ocurre en pacientes con enfermedad renal crónica (ERC). Los objetivos de este estudio fueron investigar las características clínicas de los pacientes con ERC y elevación de los niveles séricos de GGT, así como el valor de predicción de esta enzima sobre la mortalidad. Material y métodos: Estudio retrospectivo de observación en una cohorte de pacientes con ERC estadios 4-5 prediálisis. Se recogieron los parámetros demográficos, clínicos y bioquímicos de interés pronóstico y se utilizaron para caracterizar a los pacientes con elevación de GGT (>36 UI/l). Mediante regresión de Cox se analizó la asociación de los valores basales de GGT y fosfatasa alcalina (FA) sobre la mortalidad por cualquier causa. Resultados: Se incluyó a 909 pacientes (edad media 65±15 años). Se observaron niveles elevados de GGT o FA en 209 (23%) y 172 (19%) pacientes, respectivamente, y elevación simultánea en 68 (7%) pacientes. Niveles elevados de GGT se asociaron con mayor comorbilidad y un perfil bioquímico con concentraciones más elevadas de ácido úrico, triglicéridos, transaminasa glutámico-pirúvica, ferritina, y proteína C reactiva. Durante el seguimiento fallecieron 365 pacientes (40%). Niveles elevados de GGT (hazard ratio [HR]=1,39; IC 95%: 1,09-1,78; p=0,009), o de FA (HR=1,31; IC 95%: 1,02-1,68; p=0,038) se asociaron de forma independiente con la mortalidad. Conclusiones: Niveles séricos elevados de GGT o de FA son predictores independientes de mortalidad en pacientes con ERC (AU)

Introduction: High serum gamma-glutamyl transferase (GGT) levels are associated with increased mortality in the general population. However, this association has scarcely been investigated in patients with chronic kidney disease (CKD). This study aims to investigate the clinical characteristics of CKD patients with abnormally elevated serum GGT, and its value for predicting mortality. Material and methods: Retrospective observational study in a population cohort of adults with stage 4-5 CKD not yet on dialysis. Demographic, clinical, and biochemical parameters of prognostic interest were recorded and used to characterise CKD patients with high levels of GGT (>36 IU/l). Cox proportional hazard regression models were used to analyse the influence of baseline serum GGT and alkaline phosphatase (ALP) levels on mortality for whatever reason. Results: The study group consisted of 909 patients (mean age 65±15 years). Abnormally elevated GGT or ALP levels at baseline were observed in 209 (23%) and 172 (19%) patients, respectively, and concomitant elevations of GGT and ALP in 68 (7%). High GGT levels were associated with higher comorbidity burden, and a biochemical profile characterised by higher serum concentration of uric acid, triglycerides, alanine aminotransferase, ferritin, and C-reactive. During the study period, 365 patients (40%) died (median survival time=74 months). In adjusted Cox regression models, high levels of GGT (hazard ratio [HR]=1.39;CI 95%: 1.09-1.78, P=.009) and ALP (HR=1.31; CI95%: 1.02-1.68, P=.038) were independently associated with mortality. Conclusion: High serum levels of GGT are independent predictors of mortality in CKD patients (AU)

Cómo estimar la eficacia de un captor del fósforo / How to assess the efficacy of phosphate binders

Antecedentes y objetivos: Es difícil estimar clínicamente la eficacia de los captores de fósforo (CP). Este estudio analiza los cambios que se producen en la fosfatemia y excreción urinaria de fósforo tras la administración de CP a pacientes con enfermedad renal crónica, y la utilidad de la relación entre la excreción urinaria de fósforo y la tasa de catabolismo proteico (Po/TCP) en la estimación de la eficacia de estos fármacos. Métodos: Estudio retrospectivo de observación en una cohorte de pacientes adultos con enfermedad renal crónica en estadios 4-5. Se compararon parámetros bioquímicos basales y 45-60 días después de un tratamiento con dieta baja en fósforo más CP (subgrupo «captor»=260 pacientes) o solo con los consejos dietéticos (subgrupo «control»=79 pacientes). Resultados: La carga de fósforo (excreción urinaria total) por unidad de función renal (Po/GFR) fue el parámetro mejor relacionado con la fosfatemia (R2=0,61). La cifra media de Po/TCP fue de 8,2±2,3mg de fósforo por gramo de proteína. Tras la administración de CP, la fosfatemia descendió un 11%, la fosfaturia un 22%, la tasa de catabolismo proteico un 7% y la Po/TCP un 15%. En el subgrupo control la Po/TCP se incrementó un 20%. La excreción urinaria de fósforo y de nitrógeno ureico se correlacionaron fuertemente de forma lineal antes y después del tratamiento con CP o tras los consejos dietéticos en el subgrupo control. Conclusiones: La Po/TCP es un parámetro que podría reflejar la absorción intestinal de fósforo y, por tanto, sus variaciones tras la administración de CP podrían servir para estimar la eficacia de estos fármacos (AU)

Background and aims: The efficacy of phosphate binders is difficult to be estimated clinically. This study analyzes the changes in serum phosphate and urinary phosphate excretion after the prescription of phosphate binders (PB) in patients with chronic kidney disease stage 4-5 pre-dialysis, and the usefulness of the ratio between total urinary phosphate and protein catabolic rate (Pu/PCR) for estimating the efficacy of PB. Methods: This retrospective observational cohort study included adult chronic kidney disease patients. Biochemical parameters were determined baseline and after 45-60 days on a low phosphate diet plus PB (‘binder’ subgroup=260 patients) or only with dietary advice (‘control’ subgroup=79 patients). Results: Phosphate load (total urinary excretion) per unit of renal function (Pu/GFR) was the best parameter correlated with serum phosphate levels (R2=0.61). Mean±SD level of Pu/PCR was 8.2±2.3mg of urinary phosphate per each g of estimated protein intake. After treatment with PB, serum phosphate levels decreased by 11%, urinary phosphate 22%, protein catabolic rate 7%, and Pu/PCR 15%. In the control subgroup, Pu/PCR increased by 20%. Urinary phosphate and urea nitrogen excretion correlated strongly, both baseline and after PB or dietary advice. Conclusions: The proposed parameter Pu/PCR may reflect the rate of intestinal phosphate absorption, and therefore, its variations after PB prescription may be a useful tool for estimating the pharmacological efficacy of these drugs (AU)

Insuficiencia renal aguda secundaria a poliarteritis nudosa / Acute kidney failure due to polyarteritis nodosa

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Regresión de calcificaciones vasculares en paciente con calcifilaxia / Regression of vascular calcification in a patient with calciphylaxis

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