Interdialytic Weight Gain Effects on Hemoglobin Concentration and Cardiovascular Events

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.

Keywords: hemodialysis; hemoglobin; interaction; interdialytic weight gain; major adverse cardiovascular events; predialysis.

Graphical abstract

Figure 1

Selection process for study population. J-DOPPS, Japanese Dialysis Outcomes and Practice Pattern Study.

Figure 2

Effect of interdialytic weight gain (IDWG) on hazard ratios (HRs) for the association between hemoglobin concentration and (a) major adverse cardiovascular events (MACEs) and (b) mortality. HRs of hemoglobin concentration of ≥10.0 g/dl–<11.0 g/dl and of ≥11.0 g/dl–<12.0 g/dl on (a) MACEs and (b) mortality by IDWG. The reference was hemoglobin concentration of ≥10.0 g/dl–<11.0 g/dl and IDWG of ≥3%–<4%. Bold values are statistically significant. MACEs included acute myocardial infarction, stroke, and all-cause mortality. RERI, relative excess risk due to interaction.