Sanne A E Peters1, Michiel L Bots2, Bernard Canaud3, Andrew Davenport4, Muriel P C Grooteman5, Fatih Kircelli6, Francesco Locatelli7, Francisco Maduell8, Marion Morena9, Menso J Nubé5, Ercan Ok6, Ferran Torres10, Mark Woodward11, Peter J Blankestijn12. 1. The George Institute for Global Health, Nuffield Department of Population Health, University of Oxford, Oxford, UK Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 3. Nephrology, Dialysis and Intensive Care Unit, CHRU, Montpellier, France Dialysis Research and Training Institute, Montpellier, France. 4. University College London, Centre for Nephrology, Royal Free Hospital, London, UK. 5. Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands. 6. Division of Nephrology, Ege University School of Medicine, Izmir, Turkey. 7. Department of Nephrology, Alessandro Manzoni Hospital, Lecco, Italy. 8. Nephrology Department, Hospital Clinic, Barcelona, Spain. 9. Dialysis Research and Training Institute, Montpellier, France Biochemistry Laboratory, CHRU, Montpellier, France U1046 INSERM, University of Montpellier I, Montpellier, France. 10. Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain Biostatistics and Data Management Platform, IDIBAPS, Hospital Clinic, Barcelona, Spain. 11. The George Institute for Global Health, Nuffield Department of Population Health, University of Oxford, Oxford, UK The George Institute for Global Health, University of Sydney, Sydney, Australia Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA. 12. Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Abstract
BACKGROUND:Mortality rates remain high for haemodialysis (HD) patients and simply increasing the HD dose to remove more small solutes does not improve survival. Online haemodiafiltration (HDF) provides additional clearance of larger toxins compared with standard HD. Randomized controlled trials (RCTs) comparing HDF with conventional HD on all-cause and cause-specific mortality in end-stage kidney disease (ESKD) patients reported inconsistent results and were at high risk of bias. We conducted a pooled individual participant data analysis of RCTs to provide the most reliable evidence to date on the effects of HDF on mortality outcomes in ESKD patients. METHODS: Individual participant data were used from four trials that compared online HDF with HD and were designed to examine the effects of HDF on mortality endpoints. Bias by informative censoring of patients was resolved. Hazard ratios (HRs) and 95% confidence intervals (95% CI) comparing the effect of online HDF versus HD on all-cause and cause-specific mortality were calculated using the Cox proportional hazard regression models. The relationship between convection volume and the study outcomes was examined by delivered convection volume standardized to body surface area. RESULTS: After a median follow-up of 2.5 years (Q1-Q3: 1.9-3.0), 769 of the 2793 participants had died (292 cardiovascular deaths). Online HDF reduced the risk of all-cause mortality by 14% (95% CI: 1%; 25%) and cardiovascular mortality by 23% (95% CI: 3%; 39%). There was no evidence for a differential effect in subgroups. The largest survival benefit was for patients receiving the highest delivered convection volume [>23 L per 1.73 m(2) body surface area (BSA) per session], with a multivariable-adjusted HR of 0.78 (95% CI: 0.62; 0.98) for all-cause mortality and 0.69 (95% CI: 0.47; 1.00) for cardiovascular disease mortality. CONCLUSIONS: This pooled individual participant analysis on the effects of online HDF compared with conventional HD indicates that online HDF reduces the risk of mortality in ESKD patients. This effect holds across a variety of important clinical subgroups of patients and is most pronounced for those receiving a higher convection volume normalized to BSA.
RCT Entities:
BACKGROUND: Mortality rates remain high for haemodialysis (HD) patients and simply increasing the HD dose to remove more small solutes does not improve survival. Online haemodiafiltration (HDF) provides additional clearance of larger toxins compared with standard HD. Randomized controlled trials (RCTs) comparing HDF with conventional HD on all-cause and cause-specific mortality in end-stage kidney disease (ESKD) patients reported inconsistent results and were at high risk of bias. We conducted a pooled individual participant data analysis of RCTs to provide the most reliable evidence to date on the effects of HDF on mortality outcomes in ESKD patients. METHODS: Individual participant data were used from four trials that compared online HDF with HD and were designed to examine the effects of HDF on mortality endpoints. Bias by informative censoring of patients was resolved. Hazard ratios (HRs) and 95% confidence intervals (95% CI) comparing the effect of online HDF versus HD on all-cause and cause-specific mortality were calculated using the Cox proportional hazard regression models. The relationship between convection volume and the study outcomes was examined by delivered convection volume standardized to body surface area. RESULTS: After a median follow-up of 2.5 years (Q1-Q3: 1.9-3.0), 769 of the 2793 participants had died (292 cardiovascular deaths). Online HDF reduced the risk of all-cause mortality by 14% (95% CI: 1%; 25%) and cardiovascular mortality by 23% (95% CI: 3%; 39%). There was no evidence for a differential effect in subgroups. The largest survival benefit was for patients receiving the highest delivered convection volume [>23 L per 1.73 m(2) body surface area (BSA) per session], with a multivariable-adjusted HR of 0.78 (95% CI: 0.62; 0.98) for all-cause mortality and 0.69 (95% CI: 0.47; 1.00) for cardiovascular disease mortality. CONCLUSIONS: This pooled individual participant analysis on the effects of online HDF compared with conventional HD indicates that online HDF reduces the risk of mortality in ESKD patients. This effect holds across a variety of important clinical subgroups of patients and is most pronounced for those receiving a higher convection volume normalized to BSA.
Authors: Richard A Ward; Jörg Vienken; Douglas M Silverstein; Stephen Ash; Bernard Canaud Journal: Clin J Am Soc Nephrol Date: 2018-03-06 Impact factor: 8.237
Authors: Charlotte Buchanan; Azharuddin Mohammed; Eleanor Cox; Katrin Köhler; Bernard Canaud; Maarten W Taal; Nicholas M Selby; Susan Francis; Chris W McIntyre Journal: J Am Soc Nephrol Date: 2016-11-10 Impact factor: 10.121