Optimal convection volume for improving patient outcomes in an international incident dialysis cohort treated with online hemodiafiltration

Abstract

Online hemodiafiltration (OL-HDF), the most efficient renal replacement therapy, enables enhanced removal of small and large uremic toxins by combining diffusive and convective solute transport. Randomized controlled trials on prevalent chronic kidney disease (CKD) patients showed improved patient survival with high-volume OL-HDF, underlining the effect of convection volume (CV). This retrospective international study was conducted in a large cohort of incident CKD patients to determine the CV threshold and range associated with survival advantage. Data were extracted from a cohort of adult CKD patients treated by post-dilution OL-HDF over a 101-month period. In total, 2293 patients with a minimum of 2 years of follow-up were analyzed using advanced statistical tools, including cubic spline analyses for determination of the CV range over which a survival increase was observed. The relative survival rate of OL-HDF patients, adjusted for age, gender, comorbidities, vascular access, albumin, C-reactive protein, and dialysis dose, was found to increase at about 55 l/week of CV and to stay increased up to about 75 l/week. Similar analysis of pre-dialysis β2-microglobin (marker of middle-molecule uremic toxins) concentrations found a nearly linear decrease in marker concentration as CV increased from 40 to 75 l/week. Analysis of log C-reactive protein levels showed a decrease over the same CV range. Thus, a convection dose target based on convection volume should be considered and needs to be confirmed by prospective trials as a new determinant of dialysis adequacy.

Introductory Chapter

“…The HDF technique, which is based on physiologic principles of diffusion and convection and the need of large volume of fluid substitution (≥23 L/session or 55-75 L/week) [23,24] together with higher blood flow rate (350 ml/min or more), is also based on the use of high-flux dialyzers. However, high-flux dialyzers are limited in their ability to remove larger-size uremic toxin such as κ and λ free light chains.…”

Update on Clinical Evidence Supporting Hemodiafiltration

“…The critical ultrafiltration volume per session (or per week) required for better patient outcome is between 20 and 22 L/session for a typical European ESKD patient. More recently, it has been shown that total ultrafiltered volume per session (or per week) acted as a continuous variable mimicking a sigmoidal dose-response curve [24].…”

“…Thus, 3 to 4 weeks are required to achieve a new steady-state and a serum concentration change [40]. Recently, it has been calculated in a large cohort of incident ESKD patients that each additional 10 L convection volume was associated with a 0.8 mg/L reduction of β2M [24].…”

“…Canaud et al [24] recently published the results of a dose-finding study exploring the optimal convection volume required to observe an increase in patient survival. This was a retrospective analysis involving 2293 incident HDF patients whose treatments were documented in the EuCliD database.…”

Hemodiafiltration: Technical and Clinical Issues

“…In the last decade, many studies have demonstrated important improvements in inflammation, cardiovascular stability, β 2 -microglobulin-related complications and many other clinical outcome measures including mortality. In particular, the most recent and well-conducted analyses have indicated that significant benefits may be achieved in dialysis patients if a higher volume of fluid exchange is obtained in postdilution HDF [6] . Looking at the single studies, and evaluating the outcomes based on the amount of convective clearance achieved, one could build a relationship with survival based on the concept of 'convective dose' ( fig.…”