Urine Tubular Biomarkers Are Associated With Natriuresis in Patients With Acute Heart Failure

Loop diuretics require functioning kidney tubules to increase the excretion of sodium into urine thereby relieving congestion in patients with acute heart failure (AHF). Whether biomarkers of kidney tubular health are associated with the natriuretic response of loop diuretics in AHF is unknown.

Spot urine sodium and 14 urine biomarkers of tubular health were measured after intravenous loop diuretic administration on the day of enrollment in 418 patients with AHF from AKINESIS (Acute Kidney Injury Neutrophil Gelatinase-Associated Lipocalin [NGAL] Evaluation of Symptomatic Heart Failure Study). The association of each biomarker with urine sodium concentration was assessed with multivariable linear regression.

The mean age was 71±12 years, 64% were men, average estimated glomerular filtration rate was 56±24 mL/min per 1.73 m², and urine sodium was 94±48 mEq/L. Higher urine concentrations of α-1-microglobulin (-5.0 mEq/L [95% CI, -8.3 to -1.6 mEq/L]), insulin-like growth factor-binding protein-7 (IGFBP-7 mEq/L; -4.1 [95% CI, -8.1 to 0.0 mEq/L]), tissue inhibitor of metalloproteinases 2 (TIMP-2; -3.6 mEq/L [95% CI, -6.5 to -0.7 mEq/L]), IGFBP-7*TIMP-2 product (-5.1 mEq/L [95% CI, -6.6 to -3.7 mEq/L]), interleukin 18 (-8.2 mEq/L [95% CI, -13.2 to -3.1 mEq/L]), kidney injury molecule 1 (-2.4 mEq/L [95% CI, -4.4 to -0.3 mEq/L]), and chemokine ligand 14 (-2.3 mEq/L [95% CI, -4.0 to -0.5 mEq/L]) were associated with lower urine sodium concentration after adjustment for confounders including estimated glomerular filtration rate and urine albumin.

Urine biomarkers of tubular health are associated with lower natriuretic response to loop diuretics in patients with AHF. Kidney tubule health may be an underappreciated contributor to diuretic responsiveness in AHF.