Types of erythropoiesis-stimulating agents and risk of end-stage kidney disease and death in patients with non-dialysis chronic kidney disease

Background. Despite the widespread use of erythropoiesisstimulating agents (ESAs) to treat anaemia, the risk of adverse outcomes associated with the use of different types of ESAs in non-dialysis chronic kidney disease (CKD) is poorly investigated. Methods. From a pooled cohort of four observational studies, we selected CKD patients receiving short-acting (epoetin a/b; n¼299) or long-acting ESAs (darbepoetin and methoxy polyethylene glycol-epoetin b; n¼403). The primary composite endpoint was end-stage kidney disease (ESKD; dialysis or transplantation) or all-cause death. Multivariable Cox models were used to estimate the relative risk of the primary endpoint between short- and long-acting ESA users. Results. During follow-up [median 3.6 years (interquartile range 2.1–6.3)], the primary endpoint was registered in 401 patients [166 (72%) in the short-acting ESA group and 235 (58%) in the long-acting ESA group]. In the highest tertile of short-acting ESA dose, the adjusted risk of primary endpoint was 2-fold higher fhazard ratio [HR] 2.07 [95% confidence interval (CI) 1.37–3.12]g than in the lowest tertile, whereas it did not change across tertiles of dose for long-acting ESA patients. Furthermore, the comparison of ESA type in each tertile of ESA dose disclosed a significant difference only in the highest tertile, where the risk of the primary endpoint was significantly higher in patients receiving short-acting ESAs [HR 1.56 (95% CI 1.09– 2.24); P¼0.016]. Results were confirmed when ESA dose was analysed as continuous variable with a significant difference in the primary endpoint between short- and long-acting ESAs for doses >105 IU/kg/week. Conclusions. Among non-dialysis CKD patients, the use of a short-acting ESA may be associated with an increased risk of ESKD or death versus long-acting ESAs when higher ESA doses are prescribed.