title: Severe acute kidney injury associated with non-steroidal anti-inflammatory drugs in cirrhosis: A case-control study.
abstract: OBJECTIVE
  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.
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Chiara
authors: C
authors: Elia
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain. Electronic address: igraupe@clinic.ub.es.
authors: Isabel
authors: I
authors: Graupera
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Rogelio
authors: R
authors: Barreto
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Elsa
authors: E
authors: Solà
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Rebeca
authors: R
authors: Moreira
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Patricia
authors: P
authors: Huelin
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Xavier
authors: X
authors: Ariza
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Cristina
authors: C
authors: Solé
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Elisa
authors: E
authors: Pose
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Anna
authors: A
authors: Baiges
authors: Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; School of Nursing, University of Barcelona, Spain.
authors: Núria
authors: N
authors: Fabrellas
authors: Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Nephrology Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain.
authors: Esteban
authors: E
authors: Poch
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Javier
authors: J
authors: Fernández
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Vicente
authors: V
authors: Arroyo
authors: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Spain.
authors: Pere
authors: P
authors: Ginès
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000401:mortality; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine
chemical_list: D000209:Acute-Phase Proteins; D000894:Anti-Inflammatory Agents, Non-Steroidal; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins
keywords: AKI; Biomarkers; Cirrhosis; Kidney failure; NGAL; NSAIDs