title: Circulating Kidney Injury Molecule 1 Predicts Prognosis and Poor Outcome in Patients With Acetaminophen-Induced Liver Injury.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: MRC Center for Drug Safety Science, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.|Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Antoine
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Venkata S
authors.initials: VS
authors.lastname: Sabbisetti
authors.affiliation: Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Francis
authors.affiliation: Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Jorgensen
authors.affiliation: Scottish Liver Transplantation Unit, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Darren G N
authors.initials: DG
authors.lastname: Craig
authors.affiliation: Scottish Liver Transplantation Unit, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Simpson
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
authors.affiliation: MRC Center for Drug Safety Science, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: B Kevin
authors.initials: BK
authors.lastname: Park
authors.affiliation: Pharmacology, Toxicology and Therapeutics, University/BHF Center for Cardiovascular Science, Edinburgh University & NPIS Edinburgh, Scottish Poisons Information Bureau, Edinburgh, United Kingdom.
authors.forename: James W
authors.initials: JW
authors.lastname: Dear
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000401:mortality* / Q000601:surgery; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D006085:Graft Survival; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D016031:Liver Transplantation / Q000379:methods / Q000401:mortality*; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D011991:Receptors, Virus / Q000378:metabolism*; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D000082:Acetaminophen; D003404:Creatinine