Higher baseline kidney injury biomarkers (KIM-1 and NAG) were associated with lower baseline urinary sodium concentration (-6.1% and -5.9% per two-fold increase; p<0.001 and p=0.001).
RCT (n=339)
Randomized
Are kidney tubule injury biomarkers associated with sodium avidity and diuretic responsiveness in patients hospitalized for acute heart failure with kidney dysfunction?
Kidney tubular injury, indicated by elevated urine KIM-1 and NAG, is associated with greater sodium avidity and impaired diuretic responsiveness in acute heart failure.
Effect estimate: -6.1% per two-fold increase in KIM-1 (95% CI -8.5%, -3.7%)
p-value: p=<0.001
Abstract Aims 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 enrollment. 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-hours 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 = 0.001, 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 0.001 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-hours (-3.6% -6.8%, -0.2%, p = 0.037 per two-fold increase). None of the biomarkers were associated with urine output over 72-hours. 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.
Horiuchi et al. (Thu,) conducted a rct in Acute heart failure with kidney dysfunction (n=339). Dopamine or nesiritide vs. Placebo was evaluated on Urinary sodium (uNa) concentration at baseline (-6.1% per two-fold increase in KIM-1, 95% CI -8.5%, -3.7%, p=<0.001). Higher baseline kidney injury biomarkers (KIM-1 and NAG) were associated with lower baseline urinary sodium concentration (-6.1% and -5.9% per two-fold increase; p<0.001 and p=0.001).