Mortality risk doubles in patients on hemodialysis with both hyponatremia and fluid overload, and is increased by more than half in the setting of hyponatremia and fluid depletion, a new study finds.

That even transient disturbances in sodium and fluid homeostasis independently contribute to poor survival is well known, but their additive effects in the dialysis population have been poorly understood. According to Jule Pinter, MD, of University Hospital Würzburg in Germany and colleagues, “in this high-risk subpopulation, adequate correction of fluid overload is especially important.”

The investigators used the European Clinical Database 5 including 72,163 patients starting hemodialysis from 25 countries to study the relationship between hyponatremia (plasma sodium less than 135 mmol/L), fluid status, and mortality risk.

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The risk of all-cause mortality due to hyponatremia significantly increased 26%, 56%, and 97% when patients’ fluid status was normal, depleted, and overloaded, respectively, compared with normonatremia and normal fluid status, Dr Pinter’s team reported in Nephrology Dialysis Transplantation. The investigators did not correct hyponatremia for glucose levels, which is a study limitation.

Hyponatremia was more frequently associated with fluid overload and normal fluid status, than fluid depletion, the investigators noted. Fluid overload and depletion were defined as more than 2.5 liters above or more than 1.1 liters below normal fluid status, respectively.

“Hyponatremia must be taken seriously in dialysis patients as it may not just be a fluid disorder, but be indicative of an underlying active disease, inflammation and protein energy wasting processes,” Dr Pinter’s team wrote.

“In brief, improvement of dialysis patients outcomes requires both strict control of fluid status, and identification and correction of causes of hyponatremia to counteract the deleterious effects on mortality of such combined disorders.”

Disclosure: This research was supported by Fresenius Medical Care. Please see the original reference for a full list of disclosures.


Pinter J, Genser B, Moissl U, et al. Hyponatraemia and fluid overload are associated with higher risk of mortality in dialysis patients. Nephrol Dial Transplant. Published online March 1, 2023. doi:10.1093/ndt/gfad041