Abstract
BACKGROUND: Kidney dysfunction, defined by measures of glomerular health, in patients hospitalized with acute heart failure (HF) is associated with death and HF readmission. We aimed to determine if kidney tubule damage and dysfunction are associated with these outcomes in acute HF. METHODS: In AKINESIS (Acute Kidney Injury Neutrophil Gelatinase-Associated Lipocalin [NGAL] Evaluation of Symptomatic Heart Failure Study), 218 individuals admitted with acute HF experiencing acute kidney injury were matched with 218 individuals without acute kidney injury. Fourteen urine tubular damage and dysfunction biomarkers were measured at hospital admission in this case-control cohort. Associations between biomarkers and the composite outcome of death or HF readmission, death alone, and HF readmission alone were evaluated adjusting for confounders including kidney and cardiac biomarkers. RESULTS: The mean age was 71±12 years, 64% were men, and mean admission estimated glomerular filtration rate was 55±23 mL/min per 1.73 m(2). There were 156 deaths or HF readmissions, 87 deaths, and 92 HF readmissions over 1 year. Each 2-fold higher level of IGFBP-7 (insulin-like growth factor binding protein-7), IGFBP-7*TIMP-2 (tissue inhibitor of metalloproteinases-2) product, KIM-1 (kidney injury molecule-1), and MCP-1 (monocyte chemoattractant protein-1) was associated with a 1.36 (95% CI, 1.13-1.64), 1.08 (95% CI, 1.01-1.14), 1.12 (95% CI, 1.02-1.24), and 1.18 (95% CI, 1.03-1.34) higher risk of death or HF readmission, respectively. IGFBP-7 was associated with death alone, whereas MCP-1 and CCL-14 (C-C motif chemokine ligand-14) were associated with HF readmission alone. CONCLUSIONS: Biomarkers of kidney tubular health are associated with risk of death and HF readmission among people admitted with acute HF independent of measures of glomerular function and cardiac risk.