Abstract
INTRODUCTION: Although predialysis hemoglobin concentration is affected by interdialytic weight gain (IDWG), the interaction between these parameters is not well understood. METHODS: Using data from the Japanese Dialysis Outcomes and Practice Pattern Study phases 1-5, we analyzed patients who underwent maintenance hemodialysis. The exposure variable was hemoglobin concentration, and the effect modifier was IDWG at baseline. These 2 categorical variables were then combined and analyzed. The primary outcome was major adverse cardiovascular events (MACEs). Hazard ratios were estimated using a Cox model for the association between exposure and MACEs after adjusting for potential confounders. We examined additive interactions between hemoglobin concentration and IDWG by calculating the relative excess risk due to interaction, which is defined as a departure from the additivity of effects. RESULTS: A total of 8234 patients were enrolled. During a median follow-up of 2.1 years, 1062 (12.9%) patients developed MACEs. In IDWG categories of <6%, adjusted hazard ratios for MACEs tended to be lower as hemoglobin concentration increased. In IDWG categories of ≥6%, point estimation of MACEs with hemoglobin concentration of ≥11.0 g/dl-<12.0 g/dl was higher than that with hemoglobin concentration of ≥10.0 g/dl-<11.0 g/dl. The relative excess risk due to interaction was 0.22 (95% confidence interval 0.02-0.42) between IDWG category of ≥6% and hemoglobin categories of ≥11.0 g/dl-<12.0 g/dl, indicating a synergistic interaction. CONCLUSIONS: The association between hemoglobin concentration and MACEs differed across IDWG. Consideration should be given to the upper limit of hemoglobin concentration in patients with high IDWG.