Anemia Treatment, Hemoglobin Variability, and Clinical Events in Patients With Nondialysis-Dependent CKD in Japan.

Abstract

Anemia management in patients with non-dialysis-dependent chronic kidney disease has attracted attention with the introduction of novel therapeutic agents; however, few studies have provided comprehensive epidemiologic information. A retrospective cohort study was conducted in adult patients with stage ≥3a non-dialysis-dependent chronic kidney disease and hemoglobin <11 g/dL (January 2013-November 2021; N=26,626) to assess longitudinal treatment patterns, hemoglobin, and iron parameters (ferritin and transferrin saturation) for anemia management. Time-dependent Cox proportional hazard models were applied to assess the risk of clinical events, including death, cardiovascular events, dialysis introduction, and red-blood-cell transfusion, associated with temporal fluctuation patterns of hemoglobin levels. The cumulative incidence of anemia treatment initiation within 12 months was 37.1%, including erythropoiesis-stimulating agents 26.5%, iron oral 16.8%, iron intravenous 5.1%, and hypoxia-inducible factor prolyl hydroxylase inhibitor 0.2%. The mean (±standard deviation) hemoglobin levels were improved from 9.9±1.2 g/dL to 10.9±1.6 g/dL at 12 months. Despite erythropoiesis-stimulating agents or hypoxia-inducible factor prolyl hydroxylase inhibitor therapy, 30.1% of patients remained hemoglobin <10 g/dL. The risks of premature death, cardiovascular events, dialysis introduction, and red-blood-cell transfusion were significantly higher in groups with consistently low hemoglobin or low-amplitude hemoglobin fluctuation around the lower limit of target hemoglobin range than in patients with target hemoglobin range (p <0.05). Likewise, significantly higher risks for dialysis introduction and red-blood-cell transfusion were associated with high-amplitude hemoglobin fluctuation across target hemoglobin range were observed. The findings underscore the importance of stable hemoglobin control within the target range to reduce the mortality and morbidity risks in patients with non-dialysis-dependent chronic kidney disease while highlighting the suboptimal and heterogeneous treatment of anemia in clinical practice.