title: 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).
abstract: OBJECTIVE
  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.
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Grodin
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; Cleveland State University, Department of Mathematics, Cleveland, Ohio.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Perez
authors.affiliation: Cleveland State University, Department of Mathematics, Cleveland, Ohio.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: Cardiovascular Division, Stony Brook University, Stony Brook, New York.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Institute of Cardiology, University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Department of Cardiology, University of Glasgow, Glasgow, United Kingdom.
authors.forename: John J
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Department of Cardiology, University of Alberta, Edmonton, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.affiliation: Cleveland State University, Department of Mathematics, Cleveland, Ohio.
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: tangw@ccf.org.
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D000072596:Hepatitis A Virus Cellular Receptor 1; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D007297:Inpatients; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D045283:Natriuretic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D016016:Proportional Hazards Models; D011991:Receptors, Virus / Q000097:blood*; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D045283:Natriuretic Agents; D011991:Receptors, Virus; D020097:Natriuretic Peptide, Brain
keywords: acute heart failure; acute kidney injury; kidney injury molecule-1; nesiritide