Early responsiveness to continuous erythropoietin receptor activator predicts renal prognosis and is determined by a novel antioxidative marker in non-dialysis chronic kidney disease: a prospective, observational, single-center study

Abstract

Background Responsiveness to erythropoietin-stimulating agents (ESAs) is important for anemia management in chronic kidney disease (CKD). We assessed the effects of a continuous erythropoietin receptor activator (CERA) on renoprotection beyond anemia management and the correlation between the responsiveness to ESAs and oxidative stress markers in CKD. Methods This single-center, prospective, observational study was conducted over 24 months. We administered CERA to 35 non-dialysis patients with hemoglobin (Hb) < 11 g/dL and examined the results of the serum diacron-reactive oxygen metabolite (dROMs) test for oxidative stress markers and biological antioxidant potential (BAP) test for antioxidant markers. We then examined the renoprotective effects of CERA and the responsiveness to CERA. Results Eighteen patients experienced renal events (doubling of serum creatinine levels, decreased estimated glomerular filtration rate to < 6.0 mL/min/1.73 m(2), or initiation of renal replacement therapy), seventeen of which survived. Kaplan-Meier analysis showed that responsiveness to CERA during the initial 3-month treatment period was a good predictor of renal events. Moreover, a high response to CERA during the 3 months independently suppressed renal events (hazard ratio, 0.344). High BAP levels at baseline were significantly associated with high responsiveness to CERA during the initial 3-month treatment period. Conclusion Responsiveness to CERA during the first 3 months was an important indicator of CKD progression. Moreover, BAP test results determined responsiveness to CERA. This is the first report to show how antioxidant levels can be a potential marker of CERA's ability to control anemia in CKD patients.