Supplementary Material for: Intra-Dialytic Hemoglobin Changes and Cardiovascular Events: A Cohort Study on Dialysis Outcomes and Practice Patterns in Japan

Background: Ultrafiltration during hemodialysis (HD) causes hemoconcentration. Little is known about the relationships between intra-dialytic changes in hemoglobin concentration and cardiovascular events. Thus, this study aimed to elucidate the relationships between intra-dialytic changes in hemoglobin concentration and cardiovascular events among HD patients. Methods: This prospective cohort study was based on the Japanese Dialysis Outcomes and Practice Pattern Study phases 4 and 5. The predictor was the ratio of post-dialysis hemoglobin concentration to pre-dialysis hemoglobin concentration (post-Hb/pre-Hb) at baseline. The primary outcome was major adverse cardiovascular events (MACEs). Hazard ratios (HRs) were estimated using a Cox model for the association between post-Hb/pre-Hb and MACEs, adjusting for potential confounders. Results: A total of 865 patients were enrolled. During a median follow-up of 2.6 years, 145 (16.8%) patients developed MACEs. Patients were divided into 4 categories according to baseline post-Hb/pre-Hb (<1.0, ≥1.0 to <1.1, ≥1.1 to <1.2, and ≥1.2). The multivariable-adjusted HRs for MACEs were 1.69 (95% CI 1.36–2.10), 1.29 (95% CI 1.10–1.51), and 1.31 (95% CI 1.02–1.68) in patients with post-Hb/pre-Hb ratios of <1.0, ≥1.0 to <1.1, and ≥1.2, respectively, compared with the reference post-Hb/pre-Hb ratio of ≥1.1 to <1.2. Cubic spline analyses revealed a U-shaped association between post-Hb/pre-Hb and MACEs. Conclusion: High and low intra-dialytic changes in hemoglobin concentration are associated with a high risk of MACEs in patients undergoing HD.