Non-Steroidal Anti-Inflammatory Drugs: What Is the Actual Risk of Chronic Kidney Disease? A Systematic Review and Meta-Analysis

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are common cause of acute kidney injury, but chronic kidney disease (CKD) risk of NSAIDs is controversial. Prior systematic reviews are outdated with some methodological flaws. We conducted this systematic review to clarify the association between chronic NSAIDs use and occurrence and/or progression of CKD. Methods: MEDLINE, Cochrane Library, Web of Science and Science direct were searched for observational and interventional studies from inception to May 2023. Qualitative synthesis was performed. The meta-analysis used pooled odds ratios (OR) and hazard ratios (HR) to estimate the association between chronic NSAID use and CKD occurrence or progression. Results: Forty studies with a total of 1757118 participants were included in the systematic review; of them 39 studies were suitable for meta-analysis. 56% of our included studies were recent, published within the last 10 years. The meta-analysis revealed a significant association between chronic NSAIDs use and CKD occurrence and progression. The pooled odds ratio was 1.24 (95% CI: 1.11-1.39, p <0.001, I-2 = 91.21%), and the pooled hazard ratio was 1.50 (95% CI: 1.31-1.7, p <0.001, I-2 = 90.77%). The pooled hazard ratio (HR) for individuals with no CKD at baseline was 1.31 (95% CI, 1.26-1.40), while for those with preexisting CKD, the HR was significantly higher at 1.67 (95% CI, 1.38-2.02). The HR for individuals with no specific chronic disease was 1.6 (95% CI, 1.32-1.94). For populations with diabetes mellitus (DM) and/or hypertension (HTN), the HR was 1.35 (95% CI, 1.27-1.43), and for those with rheumatic disease, the HR was 1.36 (95% CI, 0.88-2.10). Conclusions: Long-term NSAID use increases the risk of chronic kidney disease (CKD) occurrence and progression, especially in individuals with pre-existing CKD, who have a 67% risk compared to the general population's 60%. A patient-centered approach for safe and effective pain management is crucial, with special caution for those with pre-existing CKD.