Author + information
- Received March 13, 2015
- Revision received May 26, 2015
- Accepted June 15, 2015
- Published online October 1, 2015.
- Justin L. Grodin, MD∗,
- Antonio L. Perez, MD, MBA∗,†,
- Yuping Wu, PhD†,
- Adrian F. Hernandez, MD, MHS‡,
- Javed Butler, MD§,
- Marco Metra, MD‖,
- G. Michael Felker, MD‡,
- Adriaan A. Voors, MD¶,
- John J. McMurray, MD#,
- Paul W. Armstrong, MD∗∗,
- Robert M. Califf, MD‡,
- Randall C. Starling, MD, MPH†,
- Christopher M. O'Connor, MD‡ and
- W.H. Wilson Tang, MD∗∗ ()
- ∗Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
- †Cleveland State University, Department of Mathematics, Cleveland, Ohio
- ‡Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina
- §Cardiovascular Division, Stony Brook University, Stony Brook, New York
- ‖Institute of Cardiology, University of Brescia, Brescia, Italy
- ¶University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- #Department of Cardiology, University of Glasgow, Glasgow, United Kingdom
- ∗∗Department of Cardiology, University of Alberta, Edmonton, Canada
- ↵∗Reprint requests and correspondence:
Dr. W.H. Wilson Tang, Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4, Cleveland, Ohio 44195.
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.
The ASCEND-HF study, including the biomarker substudy, was funded by Scios Inc. Janssen Research & Development LLC retains operational responsibility for the ASCEND-HF study. Singulex, Inc. performed all plasma KIM-1 assays, and was blinded from the trial database or analyses. Statistical analyses and manuscript preparation were conducted independent of the sponsors.
Dr. Hernandez has received a research grant (significant) from Johnson & Johnson. Dr. Butler has received consultant/advisory board support (modest) from Johnson & Johnson. Dr. Metra has received consultant/advisory board support (modest) from Corthera, Daiichi, Novartis, and Serrvier. Dr. Felker has received research grants (significant) from Johnson & Johnson, Roche Diagnostics, Critical Diagnostics, and BG Medicine. Dr. Voors has received consultant/advisory board support (modest) from Johnson & Johnson, Alere, Bayer, Boehringer Ingelheim, Cardio3Biosciences, Celladon, Merck/MSD, Novartis, Servier, Trevena, and Vifor Pharma. Dr. McMurray has received research grant support (significant) from Johnson & Johnson. Dr. Armstrong has received research grant support (significant) from Johnson & Johnson, and Ortho Biotech. Dr. Califf has received research grant support (significant) from Johnson & Johnson. Dr. Starling has received research support (modest) from Johnson & Johnson; and consultant/advisory board support (modest) from Johnson & Johnson. Dr. O’Connor has received research grant support (significant) from Johnson & Johnson. Dr. Tang has reported that he has no relationships relevant to the contents of this paper to disclose. John R. Teerlink, MD, served as Guest Editor for this paper.
- Received March 13, 2015.
- Revision received May 26, 2015.
- Accepted June 15, 2015.
- American College of Cardiology Foundation