Severe acute kidney injury associated with non-steroidal anti-inflammatory drugs in cirrhosis: A case-control study

J Hepatol. 2015 Sep;63(3):593-600. doi: 10.1016/j.jhep.2015.04.004. Epub 2015 Apr 11.

Abstract

Background & aims: Non-steroidal anti-inflammatory drugs (NSAIDs) may cause impairment of kidney function in patients with cirrhosis. Investigational studies demonstrated reversibility of kidney dysfunction after drug withdrawal, but information based on clinical practice is lacking. The aim of the study was to investigate the characteristics and outcome of Acute Kidney Injury (AKI) developing in patients with cirrhosis treated with NSAIDs.

Methods: Prospective cohort study in a tertiary referral center of all patients with NSAIDs-associated AKI seen from 2002 to 2014. For comparison, three control groups of patients with hypovolemic-induced AKI, type-1 HRS and ATN, respectively, were also evaluated. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) was measured in a subset of patients.

Results: Thirty patients with cirrhosis and NSAIDs-associated AKI were identified. In 19 patients (63%) AKI was transient and kidney function rapidly recovered (4±3 days) after NSAIDs withdrawal. In the remaining 11 patients (37%) AKI was more severe and persisted during hospitalization despite drug withdrawal. Patients with persistent AKI had remarkably higher uNGAL levels compared with those of patients with transient AKI (953±1,198 vs. 83±79 μg/g of creatinine, respectively, p=0.008). Moreover, seven of the 11 patients with persistent AKI (64%) died within three months compared with only one of the 19 (5%) patients with transient AKI (p=0.001). Mortality of persistent AKI was similar in NSAIDs patients compared to control groups. The only independent predictive factor of three-month mortality was persistent AKI.

Conclusions: Patients with cirrhosis treated with NSAIDs may develop severe AKI which may be irreversible and associated with poor short-term outcome.

Keywords: AKI; Biomarkers; Cirrhosis; Kidney failure; NGAL; NSAIDs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / mortality
  • Acute-Phase Proteins / urine
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Humans
  • Lipocalin-2
  • Lipocalins / urine
  • Liver Cirrhosis / drug therapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Proto-Oncogene Proteins / urine

Substances

  • Acute-Phase Proteins
  • Anti-Inflammatory Agents, Non-Steroidal
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins