title: Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population.
abstract: BACKGROUND
  Most epidemiological studies evaluating the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and acute renal failure (ARF) found an increased risk for developing ARF while taking NSAIDs. Despite these studies, little is known about the effect of dose and duration of therapy, risk of individual NSAIDs, comorbidity, or concomitant use of other nephrotoxic drugs.
  
  
  METHODS
  This is a nested case-control study using the General Practice Research Database from the United Kingdom. Participants were 386,916 patients aged 50 to 84 years on January 1, 1997, and free of known cancer, renal disorder, cirrhosis, or systemic connective tissue disease. After validation of cases identified from this cohort, 103 patients were confirmed as idiopathic cases of ARF and compared with 5,000 controls frequency matched by age and sex.
  
  
  RESULTS
  Current users of NSAIDs had a relative risk (RR) for ARF of 3.2 (95% confidence interval [CI], 1.8 to 5.8), and the risk declined after treatment was discontinued. Increased risk was present with both short- and long-term therapy and was slightly greater among users of high doses. History of heart failure (HF), hypertension, diabetes, and hospitalizations and consultant visits in the previous year were all associated with a greater risk for ARF. There was a suggestion of a modification of the effect of NSAIDs in patients with hypertension and those with HF. Use of selected cardiovascular drugs was associated with a 5-fold increase in risk for ARF. Diuretics presented the greatest risk. Risk increased with concomitant use of NSAIDs and diuretics (RR, 11.6; 95% CI, 4.2 to 32.2) and NSAIDs and calcium channel blockers (RR, 7.8; 95% CI, 3.0 to 20.5).
  
  
  CONCLUSIONS
  NSAID users had a 3-fold greater risk for developing a first-ever diagnosis of clinical ARF compared with non-NSAID users in the general population. NSAIDs should be used with special caution in patients with hypertension and/or HF.
authors.affiliation: Centro Español de Investigación Farmacoepidemiológica, Spanish Centre for Pharmacoepidemiologic Research, Madrid, Spain. chuerta@ceife.es
authors.forename: Consuelo
authors.initials: C
authors.lastname: Huerta
authors.forename: Jordi
authors.initials: J
authors.lastname: Castellsague
authors.forename: Cristina
authors.initials: C
authors.lastname: Varas-Lorenzo
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: García Rodríguez
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000453:epidemiology*; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000009:adverse effects; D016022:Case-Control Studies; D016208:Databases, Factual; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use; D004363:Drug Utilization; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000172:deficiency / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D012306:Risk; D016037:Single-Blind Method; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D011453:Prostaglandins