Low Predialysis Plasma Calculated Osmolality Is Associated with Higher All-Cause Mortality: The Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS)

Introduction: Patients undergoing hemodialysis (HD) have higher predialysis plasma osmolality. Several studies have suggested lower osmolality to be associated with worse outcomes in patients not undergoing HD. However, no studies have examined the association between osmolality and mortality among patients undergoing HD. Objective: We aimed to examine the association between predialysis plasma calculated osmolality and all-cause mortality. Methods: This was a prospective cohort study of 1,240 patients undergoing HD participating in the Japanese Dialysis Outcomes and Practice Patterns Study phase 5 (2012-2015). The exposure was predialysis plasma osmolality, calculated as 2 x (serum sodium concentration [mmol/L]) + (serum urea nitrogen [mg/dL])/2.8 + (serum glucose [mg/dL])/18. The primary outcome was all-cause mortality. The secondary outcome was the change in systolic blood pressure (SBP) during HD. We used a marginal structural model with stabilized weights to estimate the association between calculated osmolality and all-cause mortality in the presence of time-varying confounders affected by prior exposure. Results: Mean baseline plasma calculated osmolality was 306.8 +/- 8.6 mOsm/kg. Low predialysis calculated osmolality was associated with higher mortality (adjusted hazard ratio 1.52, 95% confidence interval [CI]: 1.30-1.78 by each 10 mOsm/L lower osmolality). The association was consistent across clinically relevant subgroups. Predialysis osmolality was significantly associated with intradialytic SBP change (mean difference 0.96 [95% CI: 0.05-1.88] mm Hg per each 10 mOsm/L lower osmolality). Conclusions: Low predialysis calculated osmolality was an independent risk factor of all-cause mortality.