Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: results from a randomized controlled trial (CONTRAST).

Neelke C Van Der Weerd,Michiel L Bots,Albert H A Mazairac,Pieter M Ter Wee,Peter J Blankestijn,Claire H Den Hoedt,E Lars Penne,Muriel P C Grooteman,Renée Lévesque,Menso J Nubé,Marinus A Van Den Dorpel,Robert K Hills

doi:10.1371/journal.pone.0094434

Abstract

Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; NCT00205556), the effect of online HDF on ESA resistance and iron parameters was studied. This was a pre-specified secondary endpoint of the main trial. A 12 months' analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit). The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [−0.024 to 0.081]; P = 0.29). Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (−2.52% [−4.72 to −0.31]; P = 0.02 and −49 ng/mL [−103 to 4]; P = 0.06 respectively), although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [−0.4 to 14.5]; P = 0.06).In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance.Trial RegistrationClinicalTrials.gov NCT00205556

Highlights

In chronic hemodialysis (HD) patients, renal anemia is generally treated with erythropoiesis stimulating agents (ESA) and iron supplements
The present secondary analysis of a randomized controlled trial (RCT) showed that ESA resistance over a 12 months’ period, as measured by the mean ESA index over time, was not different between patients treated with online HDF or HD
Our overall results are in contrast with results of two cross-over studies [35,36], two observational studies [23,37] and one RCT [17] in which ESA dose and/or ESA resistance decreased and/or hemoglobin levels increased in patients treated with online HDF

Summary

Introduction

In chronic hemodialysis (HD) patients, renal anemia is generally treated with erythropoiesis stimulating agents (ESA) and iron supplements. In many HD patients, target hemoglobin levels are not reached due to a varying degree of ESA resistance. A diminished response to ESA has been associated with various factors, including (functional) iron deficiency, an impaired nutritional state and the presence of (micro)inflammation [7,8]. The microbiological purity of the dialysis fluid [9], the presence of hyperparathyroidism [10] and low dialysis adequacy [11] have been associated with ESA resistance. Hemodiafiltration (HDF) is an extracorporeal renal replacement therapy that combines diffusive and convective solute removal. In comparison with conventional HD, removal of substances in the middle molecular weight (MMW) range

Methods

Results

Conclusion