Nonselective and Cyclooxygenase-2-Selective NSAIDs and Acute Kidney Injury

Approximately 1 in 200 patients over age 65 will develop acute kidney injury within 45 days of newly initiated non-steroidal anti-inflamatory drug therapy. Patients initiating treatment with indomethacin, ibuprofen, and rofecoxib had higher rates of acute kidney injury than did individuals who received celecoxib. Clinicians need to be aware of the heterogeneity in acute kidney injury risk among cyclooxygenase (COX)-2 inhibitors.

Abstract
Objective
The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and acute kidney injury is well established, but it is less clear whether this risk is focused with specific agents. We undertook a large pharmacoepidemiologic analysis of the risk of acute kidney injury among older adults using nonselective NSAIDs or cyclooxygenase (COX)-2 inhibitors.

Methods
Medicare beneficiaries from 2 large states with drug benefit were eligible for study. Patients were included if they filled a prescription for a nonselective NSAID or COX-2 inhibitor after more than 6 months without any such prescriptions and without a previous diagnosis of acute kidney injury. Incident acute kidney injury was ascertained from hospitalization claims within 45 days of initiating nonselective NSAID or COX-2 inhibitor therapy. Adjusted proportional hazards models estimated the relative risk of acute kidney injury associated with each agent compared with celecoxib.

Results
We included 183,446 patients whose mean age was 78 years; 80% were women. Acute kidney injury was identified in 870 (0.47%) of nonselective NSAID or COX-2 inhibitor users. The agents with significantly elevated risk compared with celecoxib were indomethacin (rate ratio [RR] = 2.23; 95% confidence interval [CI], 1.70-2.93), ibuprofen (RR = 1.73; 95% CI, 1.36-2.19), and rofecoxib (RR = 1.52; 95% CI, 1.26-1.83). These findings were robust in several subgroups.

Conclusion
Acute kidney injury requiring hospitalization is a relatively rare adverse event among older adults after initiation of nonselective NSAIDs or COX-2 inhibitor treatment, observed in approximately 1 in 200 new users within 45 days. There seems to be a marked gradient of risk for acute kidney injury across agents, specifically for indomethacin, ibuprofen, and rofecoxib.

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-- Wolfgang C. Winkelmayer, MD, ScD, MPH, Sushrut S. Waikar, MD, MPH, Helen Mogun, MS, Daniel H. Solomon, MD, MPH

This article was originally published in the December 2008 issue of The American Journal of Medicine.