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

KEY POINTS: This large, contemporary study reports the management of anemia in a real-world cohort of patients with nondialysis-dependent CKD from multifaceted aspects. This study highlights the suboptimal and heterogeneous treatment of anemia in clinical practice. The findings also underscore the importance of maintaining a stable hemoglobin concentration within the target range to reduce the risk of mortality and morbidity. BACKGROUND: Anemia management in patients with nondialysis-dependent CKD has attracted attention with the introduction of novel therapeutic agents; however, few studies have provided comprehensive epidemiologic information. METHODS: A retrospective cohort study was conducted in adult patients with stage ≥3a nondialysis-dependent CKD and hemoglobin (Hb) <11 g/dl (January 2013–November 2021; N=26,626) to assess longitudinal treatment patterns, Hb, 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 Hb levels. RESULTS: 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 (±SD) Hb levels were improved from 9.9±1.2 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 Hb <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 Hb or low-amplitude Hb fluctuation around the lower limit of target Hb range than in patients with target Hb range (P < 0.05). Similarly, significantly higher risks for dialysis introduction and red blood cell transfusion were associated with high-amplitude Hb fluctuation across target Hb range were observed. CONCLUSIONS: The findings underscore the importance of stable Hb control within the target range to reduce the mortality and morbidity risks in patients with nondialysis-dependent CKD while highlighting the suboptimal and heterogeneous treatment of anemia in clinical practice.