Effect of Different Erythropoiesis-Stimulating Agents on Mortality and Kidney Disease Progression among Nondialysis-Dependent Patients with CKD

Background: Erythropoiesis-stimulating agents (ESAs) are commonly prescribed to treat anemia in both dialysis-independent and -dependent chronic kidney disease (CKD) patients. However, the clinical outcomes, particularly mortality, associated with short- and long-acting ESAs remain debated. This study investigates the prognostic implications of ESA type in a large cohort of non-dialysis CKD patients. Methods: Using the Korean National Health Insurance Service cohort database, we analyzed data from 166,673 subjects treated with epoetin α, darbepoetin, or methoxy polyethylene glycol-epoetin β (MPGB) between 2002 and 2021, with follow-up until December 31, 2022. The primary outcomes were all-cause mortality, a decline of over 40% in estimated glomerular filtration rate (eGFR), or initiation of dialysis. Results: During the follow-up period, patients receiving darbepoetin or MPGB had a significantly lower risk of renal composite outcomes compared to those receiving epoetin α (HR 0.523, 95% CI 0.489-0.561 and HR 0.266, 95% CI 0.246-0.288, respectively). However, darbepoetin use was associated with a significantly higher risk of all-cause death (HR 1.119, 95% CI 1.053-1.190), while MPGB use showed a significantly lower risk (HR 0.928, 95% CI 0.873-0.986) compared to epoetin α. Excluding subjects with missing hemoglobin data, those treated with MPGB who achieved optimal hemoglobin levels (10.0-10.9 g/dL) demonstrated a higher risk of all-cause death compared to those treated with epoetin α. Conclusion: The use of longer-acting ESAs in non-dialysis CKD patients may be associated with a reduced risk of kidney disease progression compared to short-acting ESAs. However, longer-acting ESAs may also be linked to an increased mortality rate, particularly among patients achieving optimal hemoglobin levels with MPGB.