Effect of Dialysate and Plasma Sodium on Mortality in a Global Historical Hemodialysis Cohort

Background: Excess mortality in hemodialysis patients is largely due to cardiovascular disease and is associated with abnormal fluid status and plasma sodium concentrations. Ultrafiltration facilitates the removal of fluid and sodium, whereas diffusive exchange of sodium plays a pivotal role in sodium removal and tonicity adjustment. Lower dialysate sodium may increase sodium removal at the expense of hypotonicity, reduced blood volume refilling, and intradialytic hypotension risk. Higher dialysate sodium preserves blood volume and hemodynamic stability but reduces sodium removal. In this retrospective cohort, we aimed to assess whether prescribing a dialysate sodium <= 138 mmol/L has an impact on survival outcomes compared with dialysate sodium >138 mmol/L after adjusting for plasma sodium concentration.Methods: The study population included incident hemodialysis patients from 875 Fresenius Medical Care Nephrocare clinics in 25 countries between 2010 and 2019. Baseline dialysate sodium (<= 138 or >138 mmol/L) and plasma sodium (<135, 135-142, >142 mmol/L) concentrations defined exposure status. We used multivariable Cox regression model stratified by country to model the association between time-varying dialysate and plasma sodium exposure and all-cause mortality, adjusted for demographic and treatment variables, including bioimpedance measures of fluid status.Results: In 2,123,957 patient-months from 68,196 incident hemodialysis patients with on average 3 hemodialysis sessions per week dialysate sodium of 138 mmol/l was prescribed in 63.2%, 139 mmol/l in 15.8%, 140 mmol/l in 20.7%, and other concentrations in 0.4% of patients. Most clinical centers (78.6%) used a standardized concentration. During a median follow-up of 40 months, one-third of patients (n= 21,644) died. Dialysate sodium <= 138 mmol/l was associated with higher mortality (multivariate HR for the total population (1.57, 95% CI,1.25-1.98), adjusted for plasma sodium concentrations and other confounding variables. Subgroup analysis did not show any evidence of effect modification by plasma sodium concentrations or other patient specific variables.Conclusions: These observational findings stress the need for randomized evidence to reliably define optimal standard dialysate sodium prescribing practices.