Selective and non‐selective non‐steroidal anti‐inflammatory drugs and the risk of acute kidney injury

Abstract

PURPOSE: Use of non-steroidal anti-inflammatory drugs (NSAID) is associated with risk of acute kidney injury (AKI). Risk of AKI may vary with selectivity of the NSAID, but this has not been studied in a large cohort where AKI was assessed directly from laboratory data. The objective was to compare AKI risk between selective and non-selective NSAIDs using a laboratory-based definition of AKI. METHODS: We conducted a retrospective nested case-control study in the U.S. Department of Veterans Affairs health care system. From a cohort of 1 459 271 new NSAID users, we identified 22 824 cases of AKI (97% male; mean age: 63 years), and 336 734 matched controls between 2000 and 2006. AKI was defined as a creatinine increase of greater than 50%. RESULTS: We found higher risk of AKI in new users of any single NSAID (adjusted odds ratio = 1.82; 95%CI: 1.68, 1.98) compared to non-users without recent use. The risk of AKI varied among different NSAIDs with risk generally increasing with decrease in selectivity: rofecoxib (0.95; 0.64, 1.42), celecoxib (0.96; 0.63, 1.47), meloxicam (1.13; 0.63, 2.05), etodolac (1.31; 1.08, 1.59), diclofenac (1.11; 0.84, 1.48), piroxicam (1.53; 1.05, 2.23), salsalate (1.51; 1.22, 1.87), sulindac (1.61; 1.12, 2.30), ibuprofen (2.25, 2.04, 2.49), naproxen (1.72; 1.52, 1.95), high dose aspirin (3.64; 2.46, 5.37), indomethacin (1.94; 1.56, 2.42), keterolac (2.07; 1.78, 2.41). Those using multiple NSAIDs appeared to have higher risk (2.90; 2.62, 3.22). CONCLUSIONS: This study provides evidence that risk of AKI may be lower with more selective agents than with naproxen or other non-selective NSAIDs.