Circulating Kidney Injury Molecule 1 Predicts Prognosis and Poor Outcome in Patients With Acetaminophen-Induced Liver Injury

Daniel J Antoine, Venkata S Sabbisetti, Ben Francis, Andrea L Jorgensen, Darren G N Craig, Kenneth J Simpson, Joseph V Bonventre, B Kevin Park, James W Dear

Research output: Contribution to journalArticlepeer-review

Abstract

Acute kidney injury in the context of acetaminophen (APAP; paracetamol)‐induced liver injury is an important predictor of the requirement for urgent liver transplantation (LT) to avoid death. However, the prognostic biomarker used to report kidney dysfunction (serum creatinine concentration) has suboptimal sensitivity and specificity. Kidney injury molecule 1 (KIM‐1) can be quantified in plasma as a sensitive and specific biomarker of kidney injury in both clinical and preclinical studies. Therefore, plasma KIM‐1 has potential as a sensitive prognostic biomarker of patient outcome post‐APAP overdose. In a cohort of APAP overdose patients (N = 74) with and without established liver injury, we quantified plasma KIM‐1 by immunoassay on the first day of admission to a LT unit and assessed its diagnostic performance to predict outcome compared with serum creatinine concentration. Day 1 plasma KIM‐1 was significantly elevated in patients that died or required LT, compared to spontaneous survivors (1,182 ± 251 vs. 214 ± 45 pg/mL; P < 0.005). Receiver operator characteristic analysis demonstrated the superiority of KIM‐1 (area under the curve [AUC]: 0.87; 95% confidence interval [CI]: 0.78‐0.95; 0.56 sensitivity at 0.95 specificity), compared with serum creatinine (AUC, 0.76; 95% CI: 0.64‐0.87; 0.08 sensitivity at 0.95 specificity) and other current prognostic indicators, when measured on the first day of enrollment into the study. Furthermore, KIM‐1 was found to be a statistically significant independent predictor of outcome at the 5% level (P < 0.0386) in a multivariable logistic regression model that considered all measured factors (pseudo‐R^2 = 0.895). Conclusion: Early measurement of plasma KIM‐1 represents a more sensitive predictor of patient outcome than serum creatinine concentration post‐APAP overdose. With further development, plasma KIM‐1 could significantly improve prognostic stratification. (Hepatology 2015;62:591–599
Original languageEnglish
Pages (from-to)591-599
Number of pages9
JournalHepatology
Volume62
Issue number2
Early online date18 Apr 2015
DOIs
Publication statusPublished - Aug 2015

Keywords

  • Acetaminophen
  • Adult
  • Area Under Curve
  • Biomarkers
  • Cohort Studies
  • Creatinine
  • Drug-Induced Liver Injury
  • Female
  • Graft Survival
  • Humans
  • Liver Transplantation
  • Logistic Models
  • Male
  • Membrane Glycoproteins
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • ROC Curve
  • Receptors, Virus
  • Risk Assessment
  • Severity of Illness Index
  • Survival Rate

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