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)

JACC Heart Fail. 2015 Oct;3(10):777-85. doi: 10.1016/j.jchf.2015.06.006.

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.

Keywords: acute heart failure; acute kidney injury; kidney injury molecule-1; nesiritide.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Biomarkers / blood
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Heart Failure / blood*
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Hepatitis A Virus Cellular Receptor 1
  • Hospital Mortality / trends
  • Humans
  • Inpatients
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Membrane Glycoproteins / blood*
  • Middle Aged
  • Multivariate Analysis
  • Natriuretic Agents / adverse effects
  • Natriuretic Agents / therapeutic use*
  • Natriuretic Peptide, Brain / adverse effects
  • Natriuretic Peptide, Brain / therapeutic use*
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Virus / blood*
  • Risk Assessment
  • Survival Rate
  • Treatment Outcome

Substances

  • Biomarkers
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Membrane Glycoproteins
  • Natriuretic Agents
  • Receptors, Virus
  • Natriuretic Peptide, Brain