# Kidney tubule injury is associated with sodium avidity and diuretic responsiveness in acute heart failure

## TL;DR

This study shows that kidney tubule injury in acute heart failure patients is linked to increased sodium retention and reduced response to diuretics.

## Contribution

The study reveals a novel association between kidney injury biomarkers and impaired sodium excretion and diuretic response in acute heart failure.

## Key findings

- Higher KIM-1 and NAG levels correlate with lower baseline urinary sodium and fractional excretion of sodium.
- Elevated KIM-1 is linked to reduced total sodium excretion over 72 hours.
- None of the biomarkers were associated with urine output over 72 hours.

## Abstract

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.

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.

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.

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.

Graphical AbstractAssociations between urinary kidney tubular injury biomarkers and measures of diuretic responsiveness and renal sodium avidity (spot urine sodium, spot fractional excretion of sodium, total urine sodium, and 72-h urine output) were assessed in ROSE-AHF. Higher levels of KIM-1 and NAG were associated with reduced urinary sodium excretion, whereas NGAL was not associated with any sodium measures. None of the biomarkers were associated with urine output. FeNa, fractional excretion of sodium; KIM-1, kidney injury molecule-1; NAG, N-acetyl-β-D-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; ROSE-AHF, Renal Optimization Strategies Evaluation Acute Heart Failure; uNa, urine sodium.For image description, please refer to the figure legend and surrounding text.

Associations between urinary kidney tubular injury biomarkers and measures of diuretic responsiveness and renal sodium avidity (spot urine sodium, spot fractional excretion of sodium, total urine sodium, and 72-h urine output) were assessed in ROSE-AHF. Higher levels of KIM-1 and NAG were associated with reduced urinary sodium excretion, whereas NGAL was not associated with any sodium measures. None of the biomarkers were associated with urine output. FeNa, fractional excretion of sodium; KIM-1, kidney injury molecule-1; NAG, N-acetyl-β-D-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; ROSE-AHF, Renal Optimization Strategies Evaluation Acute Heart Failure; uNa, urine sodium.