Serum osteoprotegerin in prevalent hemodialysis patients: associations with mortality, atherosclerosis and cardiac function.

BACKGROUND: To assess whether serum osteoprotegerin (OPG) and/or fetuin-A predict mortality and cardiovascular (CV) morbidity and mortality in hemodialysis patients. METHODS: Multicenter, observational, prospective study that included 220 hemodialysis patients followed up for up to 6 years. Serum OPG and fetuin-A levels were measured at baseline and their possible association with clinical characteristics, CV risk biomarkers, carotid ultrasonographic findings, as well as their association with overall and CV mortality and CV events were assessed. RESULTS: During a mean follow-up of 3.22 ± 1.91 years, there were 74 deaths (33.6%) and 86 new cardiovascular events. In the Kaplan-Meier survival analysis, the highest tertile of OPG levels was associated with higher overall mortality (p = 0.005), as well as a higher, although non-significant, incidence of CV events and CV mortality. In contrast, fetuin-A levels did not predict any of these events. OPG levels were directly associated with age, the Charlson comorbidity index (CCI), prevalent cardiovascular disease, carotid intima-media thickness, adiponectin, troponin-I and brain natriuretic peptide (BNP). OPG showed a negative correlation with left ventricular ejection fraction (LVEF) and phosphate levels. In the multivariate Cox proportional hazard analysis, all-cause mortality was associated with the highest tertile of OPG (HR:1.957, p = 0.018), age (HR:1.031, p = 0.036), smoking history (HR:2.122, p = 0.005), the CCI (HR:1.254, p = 0.004), troponin-I (HR:3.894, p = 0.042), IL-18 (HR:1.061, p < 0.001) and albumin levels (HR:0.886, p < 0.001). In the bootstrapping Cox regression analysis, the best cut-off value of OPG associated with mortality was 17.69 pmol/L (95%CI: 5.1-18.02). CONCLUSIONS: OPG, but not fetuin-A levels, are independently associated with overall mortality, as well as clinical and subclinical atherosclerosis and cardiac function, in prevalent 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.

Carotid atherosclerotic disease predicts cardiovascular events in hemodialysis patients: a prospective study.

BACKGROUND: To evaluate the predictive value of carotid atherosclerotic disease (CAD) and intima-media thickness (IMT) on incident cardiovascular disease and mortality in hemodialysis patients. METHODS: Multicenter, observational, prospective study including 110 patients, followed-up to 6 years. Carotid doppler ultrasonographic findings were classified in 4 degrees of severity: 1) IMT <0.9 mm, 2) IMT >0.9 mm, 3) carotid plaque with stenosis <50% and 4) plaque with stenosis >50%. The associations between IMT and CAD and cardiovascular events, total and cardiovascular mortality were assessed. RESULTS: 83% of the patients had atherosclerotic plaques (CAD degrees 3-4). During follow-up, 29.1% of patients experienced cardiovascular events, and 28.2% died, 38.7% of cardiovascular origin. The presence of plaques was associated with cardiovascular events (p = 0.03) while calcified plaques were associated with both cardiovascular events (p = 0.01), cardiovascular mortality (p = 0.03) and non-significantly with overall mortality (p = 0.08) in the survival analysis. Carotid IMT was not associated with outcomes. Cardiovascular events correlated with CAD severity (HR 2.27, 95% CI 1.13-4.54), age (HR 1.04, 1.01-1.06), previous cardiovascular disease (HR 1.75, 1.05-4.42), dyslipidemia (HR 2.25, 1.11-4.53), lipoprotein (a) (HR 1.01, 1.00-1.02), troponin I (HR 3.89, 1.07-14.18), fibrinogen levels (HR 1.38, 0.98-1.94) and antiplatelet therapy (HR 2.14, 1.04-4.4). In an age-adjusted multivariate model, cardiovascular events were independently associated with previous coronary artery disease (HR 3.29, 1.52-7.15) and lipoprotein (a) (HR 1.01, 1.00-1.02). CONCLUSIONS: The presence of carotid plaques and, especially, calcified plaques, are predictors of new cardiovascular events and cardiovascular mortality in hemodialysis patients, while IMT was not. The prognostic value of calcified plaques should be confirmed in future studies.

Tunneled catheters with taurolidine-citrate-heparin lock solution significantly improve the inflammatory profile of hemodialysis patients.

Mortality and morbidity are significantly higher among patients with dialysis catheters, which has been associated with chronic activation of the immune system. We hypothesized that bacteria colonizing the catheter lumen trigger an inflammatory response. We aimed to evaluate the inflammatory profile of hemodialysis patients before and after locking catheters with an antimicrobial lock solution. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha (TNF-α) were measured in serum, and levels of mRNA gene expression of IL-6, IL-10, and TNF-α were analyzed in peripheral blood mononuclear cells (PBMC). Samples were obtained at baseline and again after 3 months' use of taurolidine-citrate-heparin lock solution (TCHLS) in 31 hemodialysis patients. The rate of catheter-related bloodstream infections (CRBSI) was 1.08 per 1,000 catheter-days in the heparin period and 0.04 in the TCHLS period (P = 0.023). Compared with the baseline data, serum levels of hs-CRP and IL-6 showed median percent reductions of 18.1% and 25.2%, respectively (P < 0.01), without significant changes in TNF-α or IL-10 levels. Regarding cytokine gene expression in PBMC, the median mRNA expression levels of TNF-α and IL-6 decreased by 20% (P < 0.05) and 19.7% (P = 0.01), respectively, without changes in IL-10 expression levels. The use of TCHLS to maintain the catheter lumen sterility significantly reduces the incidence of CRBSI and improves the inflammatory profile in hemodialysis patients with tunneled catheters. Further studies are needed to evaluate the potential beneficial effects on clinical outcomes.

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.