Erythropoiesis-stimulating agent resistance is associated with diabetic kidney disease but not with diabetes: a post hoc analysis of the BRIGHTEN study

BACKGROUND: Erythropoiesis-stimulating agent (ESA) resistance in chronic kidney disease (CKD) is influenced by various factors, including diabetes. Although diabetes has been linked to ESA resistance, the BRIGHTEN study in Japan found no direct correlation. This study aimed to identify factors contributing to ESA resistance in patients with diabetes by analyzing the diabetic kidney disease (DKD) status and CKD stage. METHODS: A post hoc analysis was conducted using data from the BRIGHTEN study, a multicenter prospective observational trial investigating ESA resistance in patients with non-dialysis-dependent CKD. Patients were categorized based on diabetes status (DM vs. non-DM) and further stratified by CKD stage and presence of DKD. ESA resistance was assessed using the erythropoietin resistance index. RESULTS: No significant differences in ESA resistance were observed between the DM and non-DM groups. However, among patients with diabetes, those with DKD exhibited higher ESA resistance and required higher darbepoetin alfa (DA) dosages than did those with non-DKD nephropathy (NDKD-DM). ESA resistance and DA dosage increased with CKD progression, with notable differences in CKD stage G4 between the DKD and NDKD-DM groups. CONCLUSION: Although diabetes alone was not associated with ESA resistance, patients with DKD exhibited higher resistance, suggesting that ESA resistance is more closely linked to DKD than to diabetes itself. These findings highlight the role of proteinuria and inflammation in the ESA response, emphasizing the need for individualized anemia management strategies based on nephropathy type.