Abstract
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. To test for associations between dispensed NSAIDs and incident acute kidney injury and chronic kidney disease while controlling for other risk factors. 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. Mean total defined daily doses of prescribed NSAIDs dispensed per month in the prior 6 months. Incident outcomes were defined by diagnoses documented in health records and a military-specific digital system. 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. 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.
Highlights
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the United States in prescription and over-the-counter forms,[1] with more than 70 million NSAID prescriptions written annually.[2]
Compared with participants who received no medication, the highest exposure level was associated with significantly higher adjusted hazard ratios for acute kidney injury and chronic kidney disease, 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
There were 1 630 694 distinct NSAID prescriptions dispensed to participants during the total observation period, or a mean (SD) 2.1 (2.7) total prescriptions per person
Summary
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the United States in prescription and over-the-counter forms,[1] with more than 70 million NSAID prescriptions written annually.[2]. Clinicians who prescribe or recommend NSAIDs should weigh the benefits vs the risks for kidney health. Both selective and nonselective NSAIDs adversely affect the kidneys through prostaglandin-related effects.[5] Potential insults include impaired renal blood flow and clinically significant cytotoxic effects.[6] Signs and symptoms associated with NSAID use that can complicate blood pressure management, such as hypertension and edema, are relatively infrequent[5] but important
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