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RCT·nephrology, clinical trial, cardiology, endocrinology, internal medicine·PMC10210075

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

American Journal of Nephrology · 12 authors, 10 centres

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TL;DR

This study analyzed predictors of erythropoiesis-stimulating agent (ESA) hyporesponsiveness in a global clinical trial of 2,964 dialysis patients. It found that geographic region, particularly Latin America, was a strong, previously unreported predictor of ESA hyporesponsiveness.

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The analysis identified predictors of ESA hyporesponsiveness in the baseline population of the ASCEND-D randomized controlled trial. Using a multivariable regression model, geographic region, notably Latin America, was strongly associated with hyporesponsiveness (p < 0.001). Other strong associations included lower body mass index, lower transferrin saturation, younger age, lower albumin concentration, and higher baseline IV iron dose.

STUDY TYPE

RCT

SPECIALTY

nephrology

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100% · A

ORIGINAL PAPER

PMC10210075

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

American Journal of Nephrology

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ABSTRACT

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 2,964 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 < 0.001) with ESA hyporesponsiveness. Additional predictors of ESA hyporesponsiveness included female sex ( p = 0.010), history of heart failure ( p = 0.035), longer dialysis vintage ( p = 0.077), smoking status ( p = 0.247), aspirin use ( p = 0.121), and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use ( p = 0.214). Conclusion This is the first global HIF-PHI study to report prespecified definitions and predictors of ESA hyporesponsiveness. While most of the predictors identified in our study have been previously reported, geographic region stands out as an unexpected finding, meriting further investigation. Keywords: Anemia, Clinical trial, Dialysis, Erythropoiesis-stimulating agent, Hemoglobin

CITATION EXPORT

Iain C Macdougall, Amy M Meadowcroft, Allison Blackorby et al.. Regional Variation of Erythropoiesis-Stimulating Agent Hyporesponsiveness in the Global Daprodustat Dialysis Study (ASCEND-D). American Journal of Nephrology. (2023). https://doi.org/10.1159/000528696

AUTHORS

12 · 10 CENTRES

Iain C Macdougall, Amy M Meadowcroft, Allison Blackorby, Borut Cizman, Alexander R Cobitz, Sergio Godoy, Vivekanand Jha, Kirsten L Johansen, Gearoid McMahon, Gregorio T Obrador, Muh Geot Wong, Ajay K Singh

aDepartment of Renal Medicine, King's College Hospital, London, UK
bGSK, Collegeville, Pennsylvania, USA
cThe George Clinical, Pilar, Buenos Aires, Argentina
dGeorge Institute for Global Health, New Delhi, India
eFaculty of Medicine, Imperial College, London, UK
fManipal Academy of Higher Education, Manipal, India
gHennepin Healthcare, University of Minnesota, Minneapolis, Minnesota, USA
hBrigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
iUniversidad Panamericana School of Medicine, Mexico City, Mexico
jDepartment of Renal Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia