Intravenous loop diuretic-induced natriuresis was positively associated with larger post-diuretic spontaneous natriuresis (r=0.7, P<0.001), indicating CPDSR is not a dominant resistance mechanism.
Cohort (n=285)
Subgroup randomized
Is compensatory post-diuretic sodium reabsorption a dominant mechanism of diuretic resistance in patients with acute decompensated heart failure?
Compensatory post-diuretic sodium reabsorption is not a dominant mechanism of diuretic resistance in hypervolemic acute heart failure; rather, basal sodium avidity determines natriuresis.
Effect estimate: r = 0.7
p-value: p=<0.001
AIMS: In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown. METHODS AND RESULTS: Patients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration median 15 h (13-17) after last diuretic was 64 ± 33 mmol/L with only 4% of patients having low (<20 mmol/L) urine sodium consistent with CPDSR. Paradoxically, greater 6-h diuretic-induced natriuresis was associated with larger 18-h post-diuretic spontaneous natriuresis (r = 0.7, P < 0.001). Higher pre-diuretic urine sodium to creatinine ratio (r = 0.37, P < 0.001) was the strongest predictor of post-diuretic spontaneous natriuresis. In a subgroup of patients (n = 43) randomized to protocol-driven intensified diuretic therapies, the mean diuretic-induced natriuresis increased three-fold. In contrast to the substantial decrease in spontaneous natriuresis predicted by CPDSR, no change in post-diuretic spontaneous natriuresis was observed (P = 0.47). CONCLUSION: On a population level, CPDSR was not an important driver of diuretic resistance in hypervolemic ADHF. Contrary to CPDSR, a greater diuretic-induced natriuresis predicted a larger post-diuretic spontaneous natriuresis. Basal sodium avidity, rather than diuretic-induced CPDSR, appears to be the predominant determinate of both diuretic-induced and post-diuretic natriuresis in hypervolemic ADHF.
Cox et al. (Wed,) conducted a cohort in Acute decompensated heart failure (n=285). Intravenous loop diuretics was evaluated on Post-diuretic spontaneous natriuresis (r = 0.7, p=<0.001). Intravenous loop diuretic-induced natriuresis was positively associated with larger post-diuretic spontaneous natriuresis (r=0.7, P<0.001), indicating CPDSR is not a dominant resistance mechanism.