Associations of Abnormal Fluid Status, Plasma Sodium Disorders, and Low Dialysate Sodium with Mortality in Patients on Hemodialysis

Key Points This multicenter observational study followed 68,196 patients on hemodialysis over a decade and investigated the effect of cumulative exposure burden of abnormal fluid and sodium concentrations and dialysate sodium on mortality. Of >2 million patient-months, 61% were spent in any degree of fluid overload, 28% in severe fluid overload, and 4% in fluid depletion; 11% were spent in hyponatremia and 1% in hypernatremia; and 64% were spent on low dialysate sodium. Cumulative exposure to even mild fluid overload was associated with higher risk of death, and this association was independent of abnormal plasma sodium and low dialysate sodium. Background Abnormal fluid and plasma sodium concentrations are established prognostic factors for patients on hemodialysis. However, the cumulative effects of abnormal salt and water and potential effect modifications and the effect of dialysate sodium remain incompletely understood. Methods The study followed 68,196 patients on incident hemodialysis from 875 dialysis clinics in 25 countries over 10 years (2010–2020) investigating dose-response patterns between cumulative exposure time of fluid overload/depletion (measured by bioimpedance spectroscopy using the Fresenius Body Composition Monitor), abnormal plasma sodium levels, low dialysate sodium, and all-cause mortality. We calculated time-varying cumulative exposure (in months) of relative fluid overload (any degree; >7% or severe; >13 or >15% in women or men, respectively) and fluid depletion (<−7%), hypo- or hypernatremia (sodium <135 or >145 mmol/L, respectively), low dialysate sodium (≤138 mmol/L), and estimated hazard ratios for all-cause mortality using a multivariable Cox model. Results Of 2,123,957 patient-months, 61% were spent in any degree of fluid overload, 4% in fluid depletion, 11% in hyponatremia, and 1% in hypernatremia. Any degree of fluid overload was associated with higher all-cause mortality (hazard ratio peak at 3.42 [95% confidence intervals, 3.12 to 3.75] relative to no exposure), and this association with all-cause mortality seemed to be stronger with severe fluid overload. The risk pattern associated with hyponatremia was approximately linear in the first four patient-months and then plateaued after the fourth patient-month. We did not observe effect modification between fluid overload and hyponatremia. Conclusions Even mild fluid overload was associated with higher mortality in patients on hemodialysis. Whether more stringent fluid management results in clinical improvement requires further investigation.