Association of Serum 1,25-Dihydroxyvitamin D Levels with Erythropoietin Resistance Index-Based Relative Erythropoiesis-Stimulating Agent Hyporesponsiveness in Pre-Dialysis Chronic Kidney Disease

Erythropoiesis-stimulating agent (ESA) hyporesponsiveness is a major challenge in the management of anemia in chronic kidney disease (CKD). This study evaluated the association between serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels and ESA responsiveness in patients with pre-dialysis CKD. This retrospective cohort study included 363 adult patients with anemia and pre-dialysis CKD who received continuous erythropoietin receptor activator therapy for at least three months. ESA responsiveness was assessed using the erythropoietin resistance index (ERI). The highest ERI tertile was used to define ERI-based relative ESA hyporesponsiveness. Among 363 patients, 121 (33.3%) were classified as having relative ESA hyporesponsiveness. Serum 1,25(OH)2D levels were significantly lower in the relative ESA-hyporesponsive group. In multivariable analyses, lower serum 1,25(OH)2D levels were independently associated with relative ESA hyporesponsiveness and higher log-transformed ERI. Exploratory ROC analysis showed modest discriminative ability for identifying patients in the highest ERI tertile. Lower serum 1,25(OH)2D levels were independently associated with ERI-based relative ESA hyporesponsiveness in pre-dialysis CKD. These findings suggest that active vitamin D status may be linked to ESA responsiveness, as assessed by ERI.