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, Claire H Den Hoedt, Peter J Blankestijn, Michiel L Bots, Marinus A van den Dorpel, Renée Lévesque, Albert H A Mazairac, Menso J Nubé, E Lars Penne, Pieter M ter Wee, Muriel P C Grooteman, CONTRAST Investigators, P J Blankestijn, M L Bots, Julius Centrum, M A van den Dorpel, M P C Grooteman, M J Nubé, P M ter Wee, M Dorval, R Lévesque, M G Koopman, C J A M Konings, W P Haanstra, M Kooistra, B van Jaarsveld, T Noordzij, G W Feith, H G Peltenburg, M van Buren, J J G Offerman, Jeroen Bosch, E K Hoogeveen, F de Heer, P J van de Ven, T K Kremer Hovinga, W A Bax, J O Groeneveld, A T J Lavrijssen, A M Schrander-Van der Meer, L J M Reichert, J Huussen, P L Rensma, Y Schrama, H W van Hamersvelt, W H Boer, W H van Kuijk, M G Vervloet, I M P M J Wauters, I Sekse, Neelke C van der Weerd, Claire H Den Hoedt, Peter J Blankestijn, Michiel L Bots, Marinus A van den Dorpel, Renée Lévesque, Albert H A Mazairac, Menso J Nubé, E Lars Penne, Pieter M ter Wee, Muriel P C Grooteman, CONTRAST Investigators, P J Blankestijn, M L Bots, Julius Centrum, M A van den Dorpel, M P C Grooteman, M J Nubé, P M ter Wee, M Dorval, R Lévesque, M G Koopman, C J A M Konings, W P Haanstra, M Kooistra, B van Jaarsveld, T Noordzij, G W Feith, H G Peltenburg, M van Buren, J J G Offerman, Jeroen Bosch, E K Hoogeveen, F de Heer, P J van de Ven, T K Kremer Hovinga, W A Bax, J O Groeneveld, A T J Lavrijssen, A M Schrander-Van der Meer, L J M Reichert, J Huussen, P L Rensma, Y Schrama, H W van Hamersvelt, W H Boer, W H van Kuijk, M G Vervloet, I M P M J Wauters, I Sekse

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.

Conflict of interest statement

Competing Interests: As can be seen at the Financial Disclosure section, funding for the CONTRAST study was obtained from commercial sources (Fresenius Medical Care, Gambro Lundia AB and Roche Netherlands). However, this does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. CONSORT flow chart of patient…
Figure 1. CONSORT flow chart of patient inclusion.
Figure 2. Change in ESA index for…
Figure 2. Change in ESA index for HDF and HD.
Crude means (SE) at time of visit are depicted. P-value for mean difference in ESA index over time (HDF vs. HD) = 0.29 (based on a linear mixed-effects model including all 3122 measurements during 12 months of follow-up).

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