Haemodiafiltration and mortality in end-stage kidney disease patients

A pooled individual participant data analysis from four randomized controlled trials

Sanne A E Peters, Michiel L. Bots, Bernard Canaud, Andrew Davenport, Muriel P C Grooteman, Fatih Kircelli, Francesco Locatelli, Francisco Maduell, Marion Morena, Menso J. Nubé, Ercan Ok, Ferran Torres, Mark Woodward, Peter J. Blankestijn

Research output: Contribution to journalArticle

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 m2 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.

Original languageEnglish (US)
Pages (from-to)978-984
Number of pages7
JournalNephrology Dialysis Transplantation
Volume31
Issue number6
DOIs
StatePublished - Jun 24 2016

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Hemodiafiltration
Chronic Kidney Failure
Randomized Controlled Trials
Renal Dialysis
Mortality
Convection
Confidence Intervals
Body Surface Area
Survival
Proportional Hazards Models
Cardiovascular Diseases
Outcome Assessment (Health Care)

Keywords

  • haemodialysis

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Haemodiafiltration and mortality in end-stage kidney disease patients : A pooled individual participant data analysis from four randomized controlled trials. / Peters, Sanne A E; Bots, Michiel L.; Canaud, Bernard; Davenport, Andrew; Grooteman, Muriel P C; Kircelli, Fatih; Locatelli, Francesco; Maduell, Francisco; Morena, Marion; Nubé, Menso J.; Ok, Ercan; Torres, Ferran; Woodward, Mark; Blankestijn, Peter J.

In: Nephrology Dialysis Transplantation, Vol. 31, No. 6, 24.06.2016, p. 978-984.

Research output: Contribution to journalArticle

Peters, SAE, Bots, ML, Canaud, B, Davenport, A, Grooteman, MPC, Kircelli, F, Locatelli, F, Maduell, F, Morena, M, Nubé, MJ, Ok, E, Torres, F, Woodward, M & Blankestijn, PJ 2016, 'Haemodiafiltration and mortality in end-stage kidney disease patients: A pooled individual participant data analysis from four randomized controlled trials', Nephrology Dialysis Transplantation, vol. 31, no. 6, pp. 978-984. https://doi.org/10.1093/ndt/gfv349
Peters, Sanne A E ; Bots, Michiel L. ; Canaud, Bernard ; Davenport, Andrew ; Grooteman, Muriel P C ; Kircelli, Fatih ; Locatelli, Francesco ; Maduell, Francisco ; Morena, Marion ; Nubé, Menso J. ; Ok, Ercan ; Torres, Ferran ; Woodward, Mark ; Blankestijn, Peter J. / Haemodiafiltration and mortality in end-stage kidney disease patients : A pooled individual participant data analysis from four randomized controlled trials. In: Nephrology Dialysis Transplantation. 2016 ; Vol. 31, No. 6. pp. 978-984.
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AU - Davenport, Andrew

AU - Grooteman, Muriel P C

AU - Kircelli, Fatih

AU - Locatelli, Francesco

AU - Maduell, Francisco

AU - Morena, Marion

AU - Nubé, Menso J.

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N2 - 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 m2 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.

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