Circulating Kidney Injury Molecule-1 Levels in Acute Heart Failure Insights From the ASCEND-HF Trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure)

Justin L. Grodin, Antonio L. Perez, Yuping Wu, Adrian F. Hernandez, Javed Butler, Marco Metra, G. Michael Felker, Adriaan A. Voors, John J. McMurray, Paul W. Armstrong, Robert M. Califf, Randall C. Starling, Christopher M. O'Connor, W. H. Wilson Tang*

*Corresponding author for this work

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Abstract

OBJECTIVES This study sought to determine the relationship of KIM-1 levels with adverse clinical outcomes in acute decompensated heart failure (ADHF).

BACKGROUND Kidney injury molecule (KIM)-1 is a biomarker expressed by the nephron in acute tubular injury, and is a sensitive and specific marker for early acute kidney injury. Although commonly measured in urine, KIM-1 levels are also detectable in plasma, but its clinical and prognostic utility in ADHF is unknown.

METHODS Baseline, 48- to 72-h, and 30-day KIM-1 plasma levels were measured in 874 subjects in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial. Multivariable logistic and Cox models were used to assess the relationship between KIM-1 levels and outcomes during and after ADHF.

RESULTS The median circulating KIM-1 level at baseline was 375.4 pg/ml (interquartile range [IQR]: 237.0 to 633.1 pg/ml), at 48 to 72 h was 373.7 pg/ml (IQR: 220.3 to 640.5 pg/ml), and at 30 days was 382.6 pg/ml (IQR: 236.5 to 638.0 pg/ml). There were no associations between KIM-1 levels and any 30-day outcomes. In univariable analysis, both baseline and follow-up KIM-1 were associated with greater 180-day mortality risk. However, after adjusting for blood urea nitrogen or creatinine in addition to established risk predictors from ASCEND-HF, higher KIM-1 at all time points during hospitalization was not associated with in-hospital or post-discharge outcomes (all p > 0.05), but KIM-1 levels measured at 30 days were associated independently with 180-day mortality (hazard ratio: 1.49; p = 0.04).

CONCLUSIONS In our study cohort, circulating KIM-1 at baseline and during hospitalization was not associated with adverse clinical outcomes in ADHF after adjusting for standard indices of kidney function. (C) 2015 by the American College of Cardiology Foundation.

Original languageEnglish
Pages (from-to)777-785
Number of pages9
JournalJACC. Heart failure
Volume3
Issue number10
DOIs
Publication statusPublished - Oct-2015

Keywords

  • acute heart failure
  • acute kidney injury
  • kidney injury molecule-1
  • nesiritide
  • WORSENING RENAL-FUNCTION
  • CYSTATIN-C
  • CARDIORENAL SYNDROME
  • TUBULAR INJURY
  • BIOMARKER
  • DYSFUNCTION
  • MORTALITY
  • KIM-1
  • CELLS
  • RISK

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