Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Dialysis-Dependent Patients with Anaemia of Chronic Kidney Disease: A Retrospective Observational Study.

Abstract

Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) in patients with anaemia of chronic kidney disease may lead to increased ESA doses to achieve target haemoglobin levels; however, elevated doses may be associated with increased mortality. Furthermore, patients with hyporesponsiveness to ESAs have poorer clinical outcomes than those who respond well to ESAs. Incidence and clinical characteristics of patients with ESA hyporesponsiveness were explored in a real-world setting. This was a retrospective study of electronic medical records of adults with stage5 chronic kidney disease receiving renal replacement therapy and ESA treatment, from 1 January 2015 to 31 December 2021. The primary objective was ESA hyporesponsiveness rate/1000days, with a hyporesponsive event defined as ESA use at an elevated dose, according to National Institute for Health and Care Excellence (NICE) criteria. Other hyporesponsiveness definitions applied were erythropoietin resistance index-defined ESA hyporesponsiveness (ERI) Kidney DiseaseImproving Global Outcomes (KDIGO) and a clinical practicality algorithm. In total, 85,259 patients were included in the analysis; 59.9% were male, median (interquartile range) ESA starting dose was 733.3 (400.0, 1200.0)IU/week and follow-up duration was 2.2 (1.0, 4.2) years. Incidence of ESA hyporesponsiveness varied when applying different definitions; NICE 0.05/1000days (5.2% of patients), ERI 0.40/1000days (40.7%), KDIGO 0.15/1000days (15.4%), and clinical practicality algorithm 0.48/1000days (47.9%). ESA doses remained higher in hyporesponsive versus responsive patients, yet haemoglobin levels were similar between groups. The results from this study, which applied multiple hyporesponsiveness definitions to a large, geographically diverse population of patients with anaemia of CKD, showed variation in ESA hyporesponsiveness incidence rates depending on definitions used and higher ESA doses in hyporesponsive versus responsive patients. These results underscore the need for individualised clinical assessment and thorough evaluation when considering ESA dose adjustments to reach haemoglobin targets. Graphical abstract available for this article. NCT05530291.