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

PLoS One. 2014 Apr 17;9(4):e94434. doi: 10.1371/journal.pone.0094434. eCollection 2014.

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 registration: ClinicalTrials.gov NCT00205556.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Resistance*
  • Female
  • Hematinics / pharmacology*
  • Hemodiafiltration / methods*
  • Hemoglobins / metabolism
  • Humans
  • Iron / metabolism
  • Male
  • Middle Aged
  • Treatment Outcome

Substances

  • Hematinics
  • Hemoglobins
  • Iron

Associated data

  • ClinicalTrials.gov/NCT00205556

Grants and funding

CONTRAST is financially supported by a grant from the Dutch Kidney Foundation (Nierstichting Nederland, grant C02.2019) and unrestricted grants from Fresenius Medical Care (The Netherlands) and Gambro Lundia AB (Sweden). Additional support was received from the Dr. E.E. Twiss Fund, Roche Netherlands, the International Society of Nephrology/Baxter Extramural Grant Program, and the Dutch Organization for Health Research and Development (ZonMW, grant 17088.2802). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.