Abstract
INTRODUCTION: Greater sodium avidity in acute heart failure (AHF) is associated with worse outcomes, but whether kidney tubule injury is associated with sodium avidity and impaired diuretic responsiveness remains underexplored. METHODS: We evaluated 339 participants from the ROSE-AHF trial, which enrolled patients hospitalized for AHF with kidney dysfunction and randomized them to the dopamine, nesiritide, or placebo group. Urinary kidney injury molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) were measured at enrolment. Associations between these biomarkers and urinary sodium (uNa) concentration at baseline, fractional excretion of sodium (FeNa), as well as total uNa output and urine output over 72-h were assessed using multivariable regression models. RESULTS: Higher KIM-1 and NAG values at baseline were associated with lower uNa concentration at baseline [-6.1% (-8.5%, -3.7%), P < 0.001 and -5.9% (-9.2%, -2.6%), P & .001, respectively, per two-fold increase in each biomarker]. Higher baseline KIM-1 and NAG were also associated with lower FeNa [-6.1% (-8.5%, -3.6%), P < .001 and -5.2% (-8.6%, -3.6%), P = 0 .001, respectively, per two-fold increase in each biomarker]. Higher baseline KIM-1 was associated with lower total uNa excretion over 72-h [-3.6% (-6.8%, -0.2%), P = 0.037 per two-fold increase]. None of the biomarkers were associated with urine output over 72-h. CONCLUSION: Kidney tubular injury, as assessed by urine KIM-1 and NAG, is associated with greater sodium avidity and higher KIM-1 is associated with impaired diuretic responsiveness in AHF.