Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials.
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.



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.



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.



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.
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.
Sanne A E
SA
Peters
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Michiel L
ML
Bots
Nephrology, Dialysis and Intensive Care Unit, CHRU, Montpellier, France Dialysis Research and Training Institute, Montpellier, France.
Bernard
B
Canaud
University College London, Centre for Nephrology, Royal Free Hospital, London, UK.
Andrew
A
Davenport
Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
Muriel P C
MP
Grooteman
Division of Nephrology, Ege University School of Medicine, Izmir, Turkey.
Fatih
F
Kircelli
Department of Nephrology, Alessandro Manzoni Hospital, Lecco, Italy.
Francesco
F
Locatelli
Nephrology Department, Hospital Clinic, Barcelona, Spain.
Francisco
F
Maduell
Dialysis Research and Training Institute, Montpellier, France Biochemistry Laboratory, CHRU, Montpellier, France U1046 INSERM, University of Montpellier I, Montpellier, France.
Marion
M
Morena
Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
Menso J
MJ
Nubé
Division of Nephrology, Ege University School of Medicine, Izmir, Turkey.
Ercan
E
Ok
Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain Biostatistics and Data Management Platform, IDIBAPS, Hospital Clinic, Barcelona, Spain.
Ferran
F
Torres
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.
Mark
M
Woodward
Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Peter J
PJ
Blankestijn
D000368:Aged; D002423:Cause of Death / Q000639:trends; D005060:Europe / Q000453:epidemiology; D005260:Female; D017583:Hemodiafiltration / Q000379:methods*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000379:methods; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends
ESKD; clinical trial; epidemiology; haemodiafiltration; haemodialysis