Assessment of a serum calcification propensity test for the prediction of all-cause mortality among hemodialysis patients.

BACKGROUND: Vascular calcification is a major contributor to the high cardiac burden among hemodialysis patients. A novel in vitro T50-test, which determines calcification propensity of human serum, may identify patients at high risk for cardiovascular (CV) disease and mortality. We evaluated whether T50 predicts mortality and hospitalizations among an unselected cohort of hemodialysis patients. METHODS: This prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 dialysis centers in Spain. T50 and fetuin-A were determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database. After their baseline T50 measurement, patients were followed for two years for the occurrence of all-cause mortality, CV-related mortality, all-cause and CV-related hospitalizations. Outcome assessment was performed with proportional subdistribution hazards regression modelling. RESULTS: Patients who died during follow-up had a significantly lower T50 at baseline as compared to those who survived (269.6 vs. 287.7 min, p = 0.001). A cross-validated model (mean c statistic: 0.5767) identified T50 as a linear predictor of all-cause-mortality (subdistribution hazard ratio (per min): 0.9957, 95% CI [0.9933;0.9981]). T50 remained significant after inclusion of known predictors. There was no evidence for prediction of CV-related outcomes, but for all-cause hospitalizations (mean c statistic: 0.5284). CONCLUSION: T50 was identified as an independent predictor of all-cause mortality among an unselected cohort of hemodialysis patients. However, the additional predictive value of T50 added to known mortality predictors was limited. Future studies are needed to assess the predictive value of T50 for CV-related events in unselected hemodialysis patients.

Reanálisis del estudio ESHOL: mortalidad por todas las causas considerando riesgos de competición y tiempo-dependientes para trasplante renal / ESHOL study reanalysis: All-cause mortality considered by competing risks and time-dependent covariates for renal transplantation

Introducción: El estudio ESHOL ha demostrado que la hemodiafiltraciónon line (HDF-OL) posdilución reduce la mortalidad por todas las causas respecto a la hemodiálisis (HD) en pacientes prevalentes. Sin embargo, durante el periodo de observación, 355 pacientes finalizaron prematuramente el estudio, de acuerdo con el diseño del mismo. Estos pacientes fueron censurados en el momento de la finalización prematura. Objetivos: El objetivo de este estudio fue investigar los eventos de los pacientes que abandonaron el estudio. Métodos: Reanalizar los datos de supervivencia utilizando la población por intención de tratar en los 3 años de seguimiento. Los datos fueron analizados considerando también el trasplante renal como evento competitivo de la muerte del paciente. Resultados: Durante el seguimiento, 207 pacientes fallecieron durante el tratamiento y 47 después de abandonar el estudio. Comparados con aquellos pacientes que se mantuvieron en HD, los que fueron aleatorizados a HDF-OL tuvieron una mortalidad total menor (12,4 vs. 9,46 por 100/pacientes/año, hazard ratio [HR] e IC 95%: 0,76 [0,59-0,98]; p=0,031). La mortalidad total por todas las causas, teniendo en consideración el riesgo competitivo del trasplante renal y tiempo-dependiente, mostró en el análisis de Cox tiempo-dependiente resultados similares al análisis principal con un HR de 0,77 (0,60-0,99; p=0,043). Conclusiones: Los resultados del reanálisis del estudio ESHOL se confirman cuando se aplica el análisis en la población por intención de tratar sin censurar ninguna observación y considerando la mortalidad por todas las causas dependiente del tiempo y del riesgo competitivo del trasplante renal (AU)

Background: The ESHOL study showed that post-dilution online haemodiafiltration (OL-HDF) reduces all-cause mortality versus haemodialysis. However, during the observation period, 355 patients prematurely completed the study and, according to the study design, these patients were censored at the time of premature termination. Methods: The aim of this study was to investigate the outcome of patients who discontinued the study. Results: During follow-up, 207 patients died while under treatment and 47 patients died after discontinuation of the study. Compared with patients maintained on haemodialysis, those randomised to OL-HDF had lower all-cause mortality (12.4 versus 9.46 per 100 patient-years, hazard ratio and 95%CI: 0.76; [0.59-0.98], P= 0.031). For all-cause mortality by time-dependent covariates and competing risks for transplantation, the time-dependent Cox analysis showed very similar results to the main analysis with a hazard ratio of 0.77 (0.60-0.99, P= 0.043). Conclusion: The results of this analysis of the ESHOL trial confirm that post-dilution OL-HDF reduces all-cause mortality versus haemodialysis in prevalent patients. The original results of the ESHOL study, which censored patients discontinuing the study for any reason, were confirmed in the present ITT population without censures and when all-cause mortality was considered by time-dependent and competing risks for transplantation (AU)

ESHOL study reanalysis: All-cause mortality considered by competing risks and time-dependent covariates for renal transplantation.

BACKGROUND: The ESHOL study showed that post-dilution online haemodiafiltration (OL-HDF) reduces all-cause mortality versus haemodialysis. However, during the observation period, 355 patients prematurely completed the study and, according to the study design, these patients were censored at the time of premature termination. METHODS: The aim of this study was to investigate the outcome of patients who discontinued the study. RESULTS: During follow-up, 207 patients died while under treatment and 47 patients died after discontinuation of the study. Compared with patients maintained on haemodialysis, those randomised to OL-HDF had lower all-cause mortality (12.4 versus 9.46 per 100 patient-years, hazard ratio and 95%CI: 0.76; [0.59-0.98], P= 0.031). For all-cause mortality by time-dependent covariates and competing risks for transplantation, the time-dependent Cox analysis showed very similar results to the main analysis with a hazard ratio of 0.77 (0.60-0.99, P= 0.043). CONCLUSION: The results of this analysis of the ESHOL trial confirm that post-dilution OL-HDF reduces all-cause mortality versus haemodialysis in prevalent patients. The original results of the ESHOL study, which censored patients discontinuing the study for any reason, were confirmed in the present ITT population without censures and when all-cause mortality was considered by time-dependent and competing risks for transplantation.

High-efficiency postdilution online hemodiafiltration reduces all-cause mortality in hemodialysis patients.

Retrospective studies suggest that online hemodiafiltration (OL-HDF) may reduce the risk of mortality compared with standard hemodialysis in patients with ESRD. We conducted a multicenter, open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-efficiency postdilution OL-HDF (n=456). The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular mortality, all-cause hospitalization, treatment tolerability, and laboratory data. Compared with patients who continued on hemodialysis, those assigned to OL-HDF had a 30% lower risk of all-cause mortality (hazard ratio [HR], 0.70; 95% confidence interval [95% CI], 0.53-0.92; P=0.01), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44-1.02; P=0.06), and a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21-0.96; P=0.03). The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death. The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF. In conclusion, high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis.

Design and patient characteristics of ESHOL study, a Catalonian prospective randomized study.

BACKGROUND: Retrospective studies showed that online hemodiafiltration (OL-HDF) is associated with a risk reduction of mortality over standard hemodialysis (HD) in patients with end-stage renal disease. Until now, no information was available from prospective randomized clinical trials. METHODS: A prospective, randomized, multicenter, open study was designed to be conducted in HD units from Catalonia (Spain). The aim of the study is to compare 3-year survival in prevalent end-stage renal disease patients randomized to OL-HDF or to continue on standard HD. The minimum sample size was calculated according to Catalonian mortality of patients on dialysis and assuming a risk reduction associated with OL-HDF of 35% (1-sided p<0.05 and a statistical power of 0.8) and a rate of dropout due to renal transplantation or loss to follow-up of 30%. RESULTS: From May 2007 to September 2008, 906 patients were included and randomized to OL-HDF (n=456) or standard HD (n=450). Demographics and analytical data at the time of randomization were not different between both groups of patients. Patients will be followed during a 3-year period. CONCLUSION: The present study will contribute to evaluating the benefit for patient survival of OL-HDF over standard HD.