High Dose of NSAIDs May Increase Kidney Disease Risk

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Exposure to high doses of nonsteroidal anti-inflammatory drugs (NSAIDs) shows a modest but significant association with kidney disease in a military population, reports a study in the open-access journal JAMA Network Open.

The retrospective analysis included data on more than 764,000 US Army soldiers on active duty from 2011 through 2014. Eighty-six percent of participants were men; median age was 27 years. Dispensing and dose of prescription NSAIDs were evaluated for association with incident diagnoses of acute kidney injury (AKI) and chronic kidney disease (CKD).

The participants received a total of 1.6 million distinct NSAID prescriptions during the observation period: mean 2.1 prescriptions per person. Nearly two-thirds of personnel had no NSAID prescriptions in the previous 6 months. About 18% were dispensed 1 to 7 mean total daily defined doses (DDDs) per month, while 16% received more than 7 DDDs. There were a total of 2356 AKI outcomes, affecting 0.3% of participants; and 1634 CKD outcomes, affecting 0.2% of participants.

Participants with 7 or more DDDs per month had significant increases in both kidney disease outcomes: adjusted hazard ratio 1.2 for both AKI and CKD. At this level of exposure, there were 17.6 additional cases of AKI and 30.0 additional cases of CKD per 100,000 exposed individuals. Obese individuals were at significantly increased risk of both outcomes: adjusted hazard ratio 1.5 for AKI and 1.6 for CKD. The hazards were more than doubled for individuals with a history of hypertension and rhabdomyolysis. For diabetes, the hazard ratio was 1.8 for both outcomes.

Most studies of NSAID associations with kidney disease have focused on older adults or patients with chronic diseases. There has been little concern about the renal effects of these widely used medications in young, healthy adults. Some studies have suggested a possible increase in kidney disease risk among NSAID users engaging in endurance exercise.

This large study of Army personnel finds “modest but statistically significant” associations between high doses of NSAIDs and the risk of acute and chronic kidney disease outcomes. “Dosage reduction represents an approach that may decrease associated kidney disease outcome rates,” the researchers write. They also note the contribution of modifiable factors such as body mass index and hypertension [Nelson DA, et al. Association of nonsteroidal anti-inflammatory drug prescriptions with kidney disease among active young and middle-aged adults. JAMA Netw Open 2019; 2 (2):e187896. doi:10.1001/jamanetworkopen.2018.7896].