Regional Variation of Erythropoiesis-Stimulating Agent Hyporesponsiveness in the Global Daprodustat Dialysis Study (ASCEND-D)

American Journal of Nephrology

Patient-Oriented, Translational Research: Research Article

Macdougall I.C. · Meadowcroft A.M. · Blackorby A. · Cizman B. · Cobitz A.R. · Godoy S. · Jha V. · Johansen K.L. · McMahon G. · Obrador G.T. · Wong M.G. · Singh A.K.

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Article / Publication Details Abstract

Introduction: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) affects 10–15% of the chronic dialysis population. We explored baseline characteristics and predictors of ESA hyporesponsiveness in a global randomized cardiovascular outcomes study comparing an investigational hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), daprodustat, with conventional ESA treatment. Methods: ASCEND-D (NCT02879305) recruited 2964 chronic dialysis patients receiving ESA treatment (standardized to weekly intravenous [IV] epoetin) who were iron replete at baseline. The primary ESA hyporesponsiveness definition was an ESA Resistance Index (ERI, ESA Units/kg/week/hemoglobin g/l) ≥2 or IV standardized ESA dose ≥450 Units/kg/week. Predictors of ESA hyporesponsiveness were determined using a multivariable regression model. Alternative hyporesponder definitions were explored. Results: Using the primary definition, 354 (12%) patients were ESA hyporesponsive. Geographic region, notably Latin America, lower baseline body mass index and transferrin saturation, younger age, lower albumin concentration, and a higher baseline IV iron dose were identified as strongly associated (P

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