Differential Impact of Ultrafiltration and Diuretics on Urine Sodium Excretion in Acute Heart Failure: Insights from CARRESS-HF

Abstract

Introduction By blocking Na resorption in the thick ascending limb of the nephron, loop diuretics (LD) mediate volume loss through natriuresis. In contrast, extracorporeal isotonic volume removal by ultrafiltration (UF) is not renally mediated. Whether these therapies have a differential effect on renal sodium excretion in acute heart failure (AHF) is unknown. Hypothesis Diuretic-mediated decongestion will be associated with more sodium excretion than UF mediated decongestion. Methods A per-protocol analysis of CARRESS-HF (N=188) was performed. Participants were included if they had spot urine Na measured in the core lab and either randomized to UF and had UF output collected without concomitant intravenous LD use, or if randomized to the LD-based pharmacological arm and had urine but not UF output collected. There were N=61, 55, and 51 participants meeting this criteria at baseline, 24 h and 96 h, respectively. Mixed effects modelling determined the association of treatment on serial parameters. Results There were N=20 in the UF arm (age 67y [59-82], 80% male, 55% NICM, Cr 2.1 mg/dL [1.7-2.4], Na 137 mmol/L [134-139]) and N=41 in the pharmacological arm (age 65y [59-76], 73% male, 54% NICM, Cr 2.4 mg/dL [1.9-2.7], Na 138 mmol/L [135-140]). UF was associated with more relative weight loss by 96 h (%*time, P-interaction=0.003), lower urine sodium concentration over time by 24 and 96 h (UNa*time, P-interaction Conclusions Ultrafiltration, without concomitant LD use, is associated with less urinary sodium excretion in comparison to LD-based pharmacological decongestion in AHF. Yet, UF was also associated with greater weight loss, which may be reflective of greater cumulative sodium removal via UF. These observations highlight the differential response to sodium renal handling from extracorporeal volume removal than from LDs.