Long term fluid volume fluctuations and mortality in kidney failure patients on long term hemodialysis treatment.

Zoccali, Carmine; Tripepi, Giovanni; Carioni, Paola; Mallamaci, Francesca; Savoia, Matteo; Usvyat, Len A; Maddux, Franklin W; Stuard, Stefano · Eur J Intern Med · 2025

prospective_cohort · Level II

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Abstract

The prognosis for kidney failure (KF) patients on long-term hemodialysis is poor, with fluid overload being a significant modifiable risk factor for mortality. Previous studies have focused on static measurements of fluid status, but the impact of long-term fluid fluctuations on clinical outcomes has not been thoroughly investigated. We studied a cohort of 9,178 incident KF patients at Fresenius NephroCare dialysis centers across seven countries in Europe and the Middle East. Fluid status was assessed using bioimpedance spectroscopy, providing precise measurements of the fluid overload/extracellular water (FO/ECW) ratio. Fluid overload variability was calculated as the standard deviation (SD) of the FO/ECW ratio over the first three years. Time-dependent Cox regression models, adjusted for 47 covariates, evaluated the association between fluid overload variability and one-year mortality. We also analyzed mortality risk by quartiles of fluid overload variability. Higher variability in fluid overload significantly increased mortality risk. A 1 % increase in the SD of the FO/ECW ratio was linked to a 5.3 % increase in the hazard ratio for mortality (HR: 1.053, 95 % CI: 1.045-1.062, p < 0.001). Patients in the highest quartile of fluid overload variability had a 46 % higher risk of death than those in the lowest quartile (HR: 1.46, 95 % CI: 1.28-1.67, p < 0.001). These associations remained consistent in patients who survived beyond the first and second years. Fluid overload variability significantly predicts mortality in KF patients, independent of average fluid overload levels, variability in BP pressure, and other potential confounders. Comprehensive fluid management strategies addressing both the level and variability of fluid status may improve clinical outcomes. Randomized controlled trials are necessary to confirm our hypothesis-generating findings.

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