title: Incidence and characterization of acute kidney injury after acetaminophen overdose.
abstract: Acute kidney injury (AKI) occurs in 2-10% of patients with acetaminophen (APAP) overdose. Elevation in creatinine (SCr) typically occurs 2 to 5 days after ingestion, with a mean peak on day 7, and normalization over a month. However, it remains unclear whether renal impairment occurs without hepatotoxicity. We hypothesized that APAP-associated acute renal failure occurs in patients with and without severe liver dysfunction after APAP overdose.
  
  
  
  We retrospectively evaluated all patients admitted to the Medical Intensive Care Unit at a tertiary hospital and received acetylcysteine between June 2009 and December 2014. Of the 303 patients meeting these criteria, 139 of these patients received acetylcysteine for APAP overdose. Of these patients, 138 had Model for End-Stage Liver Disease (MELD) Scores on Day 1 of admission. Using a modified MELD (m-MELD) score, only containing total bilirubin and international normalized ratio not the SCr, the median m-MELD score was calculated. Patients with m-MELD scores below the median were compared to those with scores above the median (low m-MELD score <2.9 or high m-MELD score >2.9).
  
  
  
  Baseline demographics were similar in the two groups with the exception of more hypertension in the low m-MELD group (24 vs 7%; P= .02). Time to admission was shorter in the low m-MELD group (7.9 ± 9.3 vs. 25.7 ± 29.2 hours; P= .001). The mean admission APAP level was 96.9 (±119) μg/mL in the low compared to 52.3 (±85.3) μg/mL in the high m-MELD group (P= .012). Day one SCr (1.2 ± 0.9 vs 2.7 ± 2.2 mg/dL; P< .0001) and change from baseline to highest SCr (0.2 ± 0.3 vs. 2.7 ± 3.3 mg/dL; P< .0001) were both lower in the low m-MELD group compared to the high m-MELD group. In addition, renal failure resolved upon discharge in all 2 patients (3%) with AKI in the low m-MELD group as compared to only 19 patients (44%) in the high m-MELD group.
  
  
  
  Mean day one SCr, maximum change in SCr, and lack of renal failure resolution were higher in patients with higher m-MELD scores. However, patients with low m-MELD scores presented much earlier than patients with high m-MELD scores and 26% developed AKI.
authors.affiliation: Department of Pharmaceutical Services, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, USA. Electronic address: joanna.stollings@vanderbilt.edu.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Stollings
authors.affiliation: Division of Allergy/Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, 1211 Medical Center Drive, Nashville, TN 37232, USA. Electronic address: art.wheeler@vanderbilt.edu.
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Wheeler
authors.affiliation: Division of Allergy/Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, 1211 Medical Center Drive, Nashville, TN 37232, USA. Electronic address: todd.rice@vanderbilt.edu.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Rice
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000111:Acetylcysteine / Q000627:therapeutic use; D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D062787:Drug Overdose / Q000150:complications* / Q000188:drug therapy; D005260:Female; D006801:Humans; D015994:Incidence; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008107:Liver Diseases / Q000150:complications; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D000082:Acetaminophen; D003404:Creatinine; D000111:Acetylcysteine
keywords: Acetaminophen; Acetylcysteine; Acute renal failure; Creatinine; Overdose