October 21, 2025Open Access
View Full PaperEvaluating treatment strategies for managing anaemia with erythropoiesis stimulating agent therapy in haemodialysis patients: findings from a target trial emulation using electronic health record data
Key Points
- Targeting Hb levels of 105-125 g/L was not linked to increased mortality compared to 95-115 g/L in haemodialysis patients.
- Hazard ratios indicated an increase in mortality risk for higher Hb targets, with HR 1.20 for 125-145 g/L versus 95-115 g/L.
- Using data from 8,628 patients across 10 kidney centres allowed for a robust comparison of Hb target effects.
- Findings highlight the importance of tailored ESA dosing and Hb targets in chronic kidney disease management.
Abstract
Background: Anaemia is a common complication in chronic kidney disease (CKD), often managed with erythropoiesis-stimulating agents (ESAs) and intravenous iron. However, the optimal haemoglobin (Hb) target for treatment remains uncertain. We used electronic health records to emulate a target trial comparing different Hb targets in haemodialysis patients, including ranges used in practice and those tested in earlier trials, to estimate their effects on mortality. Methods: We used electronic health records from selected UK kidney centres reporting to the Renal Registry. Eligible patients were ≥18 years, on haemodialysis for ≥3 months, and without marked ESA resistance. Using the clone-censor-weight method, we emulated a trial comparing Hb targets of (1) 105-125 g/L versus 95-115 g/L, and (2) 125-145 g/L versus 95-115 g/L. Darbepoetin dosing followed a standardized protocol with predefined dose adjustment rules and a maximum of 150 µg/week. The outcome was all-cause mortality over 8 months. Results: Among 8,628 patients from 10 kidney centres followed between 2004 and 2016; 62% were male, and the median age was 66 years (IQR 52-76). At baseline, mean Hb was 97.7 g/L (SD 15.1) and 79% were receiving darbepoetin (median dose 30 µg/week). The estimated hazard ratios for mortality were 0.92 (95% CI 0.75, 1.12) comparing the 105-125 g/L and 95-115 g/L Hb target ranges, and HR 1.20 (95% CI 0.94, 1.54) comparing the 125-145 g/L and 95-115 g/L ranges. Fewer patients remained adherent to the 125-145 g/L target range, limiting precision. Conclusions: Compared with targeting a Hb range of 95-115 g/L Hb, targeting a slightly higher range of 105-125 g/L under controlled ESA dosing was not associated with increased mortality in haemodialysis patients. However, targeting Hb levels above 125 g/L may increase mortality risk, consistent with previous trial findings.