Evaluating treatment strategies for managing anaemia with erythropoiesis stimulating agent therapy in haemodialysis patients: findings from a target trial emulation using electronic health record data

BackgroundAnaemia 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. MethodsWe 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 {micro}g/week. The outcome was all-cause mortality over 8 months. ResultsAmong 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 {micro}g/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. ConclusionsCompared 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. Lay SummaryAnaemia, or low blood haemoglobin levels, is common in people receiving dialysis for kidney disease. It is usually treated with medicines that help the body make red blood cells, along with iron therapy. But the optimal haemoglobin target is unknown. Past clinical trials did not show clear benefits from targeting higher levels and sometimes found increased risks of heart problems, so new trials are unlikely to take place. We designed a "target trial" to mimic a randomized trial using existing health records. We used data from over 8,000 UK dialysis patients between 2004 and 2016 to emulate a trial. Aiming for a moderate haemoglobin range (105-125 g/L) did not increase the risk of death compared to a lower range (95-115 g/L), whereas aiming above 125 g/L may increase risk. These findings suggest that modestly higher haemoglobin targets, if carefully managed, could improve symptoms and quality of life without increasing harm.