Association between serum hepcidin-25 and primary resistance to erythropoiesis-stimulating agents in chronic kidney disease: a secondary analysis of the HERO trial

Joel Gummer, Robert Trengove, Elaine M. Pascoe, Sunil V. Badve, Alan Cass, Philip Clarke, Stephen P. McDonald, Alicia T. Morrish, Eugenie Pedagogos, Vlado Perkovic, Donna Reidlinger, Anish Scaria, Rowan Walker, Liza A. Vergara, Carmel M. Hawley, David W. Johnson, John K. Olynyk, Paolo Ferrari, on behalf of the HERO Study Collaborative Group

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    Abstract

    Background: Pentoxifylline has been shown to increase haemoglobin levels in patients with chronic kidney disease (CKD) and erythropoietin-stimulating agent (ESA)-hyporesponsive anaemia in the Handling Erythropoietin Resistance with Oxpentifylline multicentre double-blind, randomized controlled trial. The present sub-study evaluated the effects of pentoxifylline on the iron-regulatory hormone hepcidin in patients with ESA-hyporesponsive CKD.

    Methods: This sub-study included 13 patients in the pentoxifylline arm (400 mg daily) and 13 in the matched placebo arm. Hepcidin-25 was measured by ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry following isolation from patient serum. Serum hepcidin-25, serum iron biomarkers, haemoglobin and ESA dosage were compared within and between the two groups.

    Results: Hepcidin-25 concentration at 4 months adjusted for baseline did not differ significantly in pentoxifylline versus placebo treated patients (adjusted mean difference (MD) −7.9 nmol, P = 0.114), although the difference between the groups mean translated into a >25% reduction of circulating hepcidin-25 due to pentoxifylline compared with the placebo baseline. In paired analysis, serum hepcidin-25 levels were significantly decreased at 4 months compared with baseline in the pentoxifylline group (−5.47 ± 2.27 nmol/l, P < 0.05) but not in the placebo group (2.82 ± 4.29 nmol/l, P = 0.24). Pentoxifylline did not significantly alter serum ferritin (MD 55.4 mcg/l), transferrin saturation (MD 4.04%), the dosage of ESA (MD −9.93 U/kg per week) or haemoglobin concentration (MD 5.75 g/l).

    Conclusion: The reduction of circulating hepcidin-25 due to pentoxifylline did not reach statistical significance; however, the magnitude of the difference suggests that pentoxifylline may be a clinically and biologically meaningful modulator of hepcidin-25 in dialysis of patients with ESA-hyporesponsive anaemia.

    Original languageEnglish
    Pages (from-to)548-554
    Number of pages7
    JournalNephrology
    Volume22
    Issue number7
    DOIs
    Publication statusPublished - Jul 2017

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    Gummer, J., Trengove, R., Pascoe, E. M., Badve, S. V., Cass, A., Clarke, P., McDonald, S. P., Morrish, A. T., Pedagogos, E., Perkovic, V., Reidlinger, D., Scaria, A., Walker, R., Vergara, L. A., Hawley, C. M., Johnson, D. W., Olynyk, J. K., Ferrari, P., & on behalf of the HERO Study Collaborative Group (2017). Association between serum hepcidin-25 and primary resistance to erythropoiesis-stimulating agents in chronic kidney disease: a secondary analysis of the HERO trial. Nephrology, 22(7), 548-554. https://doi.org/10.1111/nep.12815