Non-steroidal anti-inflammatory drugs in chronic kidney disease and risk of acute adverse kidney events according to route of administration.

Background: Topical non-steroidal anti-inflammatory drugs (NSAIDs) have lower risks for cardiovascular disease and gastrointestinal adverse effects compared to oral NSAIDs, but there are little data regarding their kidney risks in chronic kidney disease (CKD). We evaluated the risk of adverse acute kidney outcomes in CKD according to route of NSAID administration.

Methods: Retrospective cohort study of adults with CKD (eGFR less than 60 ml/min/1.73 m) who received prescriptions between 2015 and 2017 from a major healthcare cluster in Singapore. The adverse acute kidney outcomes were acute kidney injury (AKI) and need for nephrology specialist consult within 30 days.

Results: Among 6298 adults with CKD (mean age 72.1 ± 13.3 years and eGFR 41.9 ± 12.2 ml/min/1.73 m), systemic and topical NSAIDs were prescribed in 16.7% and 32.0%, respectively. Incident AKI (any severity), KDIGO Stage 2 or 3 AKI, and need for nephrology specialist consult occurred in 16.7%, 2.6%, and 10.6% of the study cohort, respectively. After adjusting for age, diabetes, recent cardiovascular hospitalization, baseline eGFR, RAAS blocker and diuretic, systemic NSAIDs, and topical NSAIDs, compared with the no-NSAID group, were independently associated with incident AKI [adjusted OR 1.77 (95% CI 1.46-2.15) and 1.38 (1.18-1.63), respectively]. Moderate and severe AKI (adjusted OR 1.68, 95% CI 1.09-2.58, p = 0.02) and need for nephrology consults (adjusted OR 1.41, 95% CI 1.09-1.82, p = 0.008) were also increased in systemic NSAIDs.

Conclusion: Among adults with CKD, both systemic and topical NSAIDs were independently associated with acute adverse kidney outcomes.