Determinants of impaired renal function with use of nonsteroidal anti-inflammatory drugs: the importance of half-life and other medications.
OBJECTIVE
Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with renal function, but little is known about the effects of the half-life of these agents, or the use of other medications, on renal function.


METHODS
Medication use was assessed during a standardized interview in a cross-sectional study of 802 patients undergoing total joint replacement because of osteoarthritis. Preoperative blood samples were used to estimate creatinine clearance using a standard formula that takes age, sex, and weight into account. Impaired renal function was defined as an estimated creatinine clearance less than 60 mL/min (fifteenth percentile). Multivariable logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between NSAID use (alone or in combination with diuretics or angiotensin-converting enzyme [ACE] inhibitors) and impaired renal function.


RESULTS
NSAID use per se was only marginally associated with impaired renal function (OR = 1.4; 95% CI, 0.9 to 2.2). This association was almost exclusively the result of the use of NSAIDs with a half-life of 4 or more hours (OR = 2.6; 95% CI: 1.2 to 5.7). Patients who used diuretics with NSAIDs (OR = 3.7; 95% CI: 1.7 to 8.3) or without NSAIDs (OR = 3.5; 95% CI: 1.6 to 7.6) had a higher risk of impaired renal function than did patients using NSAIDs alone (OR = 1.6) or none of these drugs (reference). A similar but less pronounced pattern was observed for ACE inhibitors.


CONCLUSIONS
NSAID-associated impaired renal function seems to be mainly the result of compounds with intermediate-long half-life. We found no evidence that the adverse effects of diuretics and ACE inhibitors on renal function were greater in those who also used NSAIDs.
Stürmer
T
T
Department of Epidemiology, German Centre for Research on Ageing, Heidelberg, Germany.
Erb
A
A
Keller
F
F
Günther
K P
KP
Brenner
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019644:Arthroplasty, Replacement, Hip; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D003430:Cross-Sectional Studies; D004232:Diuretics / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D016015:Logistic Models; D015207:Osteoarthritis, Hip / Q000453:epidemiology / Q000601:surgery
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004232:Diuretics