Effect of High-Flux Dialysis on Circulating FGF-23 Levels in End-Stage Renal Disease Patients: Results from a Randomized Trial.

Andreas Schneider,Christiane Drechsler,Bernd Genser,Hubert Scharnagl,Christoph Wanner,Tatjana Stojakovic,Detlef H Krieter,Markus P Schneider

doi:10.1371/journal.pone.0128079

Abstract

BackgroundIn patients undergoing maintenance hemodialysis (HD), increased levels of circulating fibroblast growth factor-23 (FGF-23) are independently associated with cardiovascular events and mortality. Interventional strategies aiming to reduce levels of FGF-23 in HD patients are of particular interest. The purpose of the current study was to compare the impact of high-flux versus low-flux HD on circulating FGF-23 levels.MethodsWe conducted a post-hoc analysis of the MINOXIS study, including 127 dialysis patients randomized to low-flux (n = 62) and high-flux (n = 65) HD for 52 weeks. Patients with valid measures for FGF-23 investigated baseline and after 52 weeks were included.ResultsCompared to baseline, a significant increase in FGF-23 levels after one year of low-flux HD was observed (Delta plasma FGF-23: +4026 RU/ml; p < 0.001). In contrast, FGF-23 levels remained stable in the high flux group (Delta plasma FGF-23: +373 RU/ml, p = 0.70). The adjusted difference of the absolute change in FGF-23 levels between the two treatment groups was statistically significant (p < 0.01).ConclusionsOver a period of 12 months, high-flux HD was associated with stable FGF-23 levels, whereas the low-flux HD group showed an increase of FGF-23. However, the implications of the different FGF 23 time-trends in patients on high flux dialysis, as compared to the control group, remain to be explored in specifically designed clinical trials.Trial RegistrationGerman Clinical Trials Register (DRKS) DRKS00007612.

Highlights

Despite efforts to improve outcomes in patients with end-stage renal disease (ESRD), mortality remains excessively high [1]
Over a period of 12 months, high-flux HD was associated with stable FGF-23 levels, whereas the low-flux HD group showed an increase of FGF-23
The implications of the different FGF 23 time-trends in patients on high flux dialysis, as compared to the control group, remain to be explored in designed clinical trials

Summary

Introduction

Despite efforts to improve outcomes in patients with end-stage renal disease (ESRD), mortality remains excessively high [1]. In view of the high cardiovascular risk in CKD and ESRD, strategies that are able to reduce FGF-23 levels are of particular interest. During the past two decades, more permeable high-flux dialysis membranes, which are able to eliminate low-molecular weight toxins up to 50.000 Dalton [8] have been developed. This is of clinical interest as FGF-23 is a free circulating peptide in the blood with a molecular weight of 32.000 Dalton [4, 9] which might be removed by high-flux hemodialysis (HD). In patients undergoing maintenance hemodialysis (HD), increased levels of circulating fibroblast growth factor-23 (FGF-23) are independently associated with cardiovascular events and mortality. The purpose of the current study was to compare the impact of highflux versus low-flux HD on circulating FGF-23 levels

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