Evaluating Darbepoetin Treatment Strategies for Managing Anaemia in Haemodialysis Patients: Effects on All-Cause Mortality From a Target Trial Emulation Using Electronic Health Record Data

Purpose: Anaemia is a common complication of chronic kidney disease, often treated with erythropoiesis-stimulating agents (ESAs), but the optimal haemoglobin (Hb) target remains uncertain. Using electronic health records, we emulated a target trial comparing different Hb targets in haemodialysis patients to estimate their effects on mortality. Methods: We used electronic health records from UK kidney centres reporting to the UK Renal Registry. Adults aged ≥ 18 years, receiving haemodialysis for ≥ 3 months, and without marked ESA resistance were eligible. Using the clone-censor-weight method, we emulated trials comparing Hb targets: (1) 105–125 versus 95–115 g/L and (2) 125–145 versus 95–115 g/L. Darbepoetin dosing followed a standardised protocol with predefined dose adjustments and a maximum dose of 150 μg/week. The outcome was all-cause mortality over 8 months. Results: The study included 8628 patients from 10 centres between 2004 and 2016; 62% male, median age 66 years (IQR 52–76). At baseline, mean Hb was 97.7 g/L (SD 15.1), and 79% of patients were receiving darbepoetin. The hazard ratio for mortality was 0.92 (95% CI 0.75–1.12) for the 105–125 versus 95–115 g/L comparison, and 1.20 (95% CI 0.94–1.54) for the 125–145 versus 95–115 g/L comparison. Adherence to the highest Hb target was lower, limiting precision. Conclusions: Targeting an Hb range of 105–125 g/L under controlled ESA dosing was not associated with increased mortality compared with 95–115 g/L. Targeting Hb levels above 125 g/L may increase mortality risk, consistent with previous trial findings.