Non-Steroidal Anti-Inflammatory Drugs and Risk of Acute Kidney Injury and Hyperkalemia in Older Adults: A Retrospective Cohort Study and External Validation of a Clinical Risk Model

Aim Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used analgesics among older adults. Adverse effects may be avoided by careful patient selection. We aimed to evaluate the incidence of acute kidney injury (AKI) and/or hyperkalemia, risk factors, and the accuracy of an NSAID risk prediction model in a cohort of Asian older adults. Methods We conducted a retrospective cohort study of older adults, age 65 years and above, who received prescriptions between March 2015 and December 2017 from Singapore's largest cluster of public healthcare institutions. Factors associated with 30-day incident acute kidney injury and/or hyperkalemia were evaluated with multivariable regression analysis. Calibration and discrimination of the Nash prediction model were assessed using the Hosmer-Lemeshow goodness-of-fit test and C-statistic, respectively. Results The primary outcome occurred in 16.7% of 12,798 older adults. Topical NSAIDs (adjusted OR 1.29, 95% CI 1.15-1.45), systemic NSAIDs of 1-14 days' duration (adjusted OR 1.43, 95% CI 1.27-1.62), and systemic NSAIDs > 14 days (adjusted OR 1.84, 95% CI 1.37-2.49) were independently associated with the primary outcome, compared with no NSAID. Diabetes mellitus, cardiovascular disease, lower estimated glomerular filtration rate (eGFR), and diuretics were also independently associated with increased incident AKI and/or hyperkalemia. When applied to older adults with systemic NSAIDs > 14 days (n = 305), the Nash risk model had poor calibration (p < 0.001) and poor discrimination with C-statistic 0.527 (0.438, 0.616). Conclusions Longer NSAID duration and systemic compared with topical route were associated with incremental odds for acute renal events. Further studies are required to improve the available risk model to guide NSAID prescriptions in older adults.