Association of Nonsteroidal Anti-inflammatory Drug Prescriptions With Kidney Disease Among Active Young and Middle-aged Adults

IMPORTANCE: Concern about the renal effects of nonsteroidand al anti-inflammatory drugs (NSAIDs) among young, healthy adults has been limited, but more attention may be warranted given the prevalent use of these agents. OBJECTIVE: To test for associations between dispensed NSAIDs and incident acute kidney injury and chronic kidney disease while controlling for other risk factors. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal cohort study used deidentified medical and administrative data on 764 228 active-duty US Army soldiers serving between January 1, 2011, and December 31, 2014. Analysis was conducted from August 1 to November 30, 2018. All individuals new to Army service were included in the analysis. Persons already serving in January 2011 were required to have at least 7 months of observable time to eliminate those with kidney disease histories. EXPOSURES: Mean total defined daily doses of prescribed NSAIDs dispensed per month in the prior 6 months. MAIN OUTCOMES AND MEASURES: Incident outcomes were defined by diagnoses documented in health records and a military-specific digital system. RESULTS: Among the 764 228 participants (655 392 [85.8%] men; mean [SD] age, 28.6 [7.9] years; median age, 27.0 years [interquartile range, 22.0-33.0 years]), 502 527 (65.8%) were not dispensed prescription NSAIDs in the prior 6 months, 137 108 (17.9%) were dispensed 1 to 7 mean total defined daily doses per month, and 124 594 (16.3%) received more than 7 defined daily doses per month. There were 2356 acute kidney injury outcomes (0.3% of participants) and 1634 chronic kidney disease outcomes (0.2%) observed. Compared with participants who received no medication, the highest exposure level was associated with significantly higher adjusted hazard ratios (aHRs) for acute kidney injury (aHR, 1.2; 95% CI, 1.1-1.4) and chronic kidney disease (aHR, 1.2; 95% CI, 1.0-1.3), with annual outcome excesses per 100 000 exposed individuals totaling 17.6 cases for acute kidney injury and 30.0 cases for chronic kidney disease. CONCLUSIONS AND RELEVANCE: Modest but statistically significant associations were noted between the highest observed doses of NSAID exposure and incident kidney problems among active young and middle-aged adults.