Background: Selective cyclooxygenase-2 inhibitor anti-inflammatory drugs (coxibs) are associated with adverse events, mainly gastrointestinal and cardiovascular, but renal effects are less known. Objective: To assess the renal risks of coxibs compared to placebo. Methods: We searched for randomized clinical trials that assessed renal effects of coxibs (celecoxib, etoricoxib, lumiracoxib, parecoxib, and valdecoxib) in PubMed, Embase, Scopus and other sources up to September 2022. Two independent reviewers performed study screening, data extraction, and risk of bias assessment. Random effect meta-analysis was employed to calculate the relative risks (RR) and 95% confidence intervals (CI) of renal effects of coxibs compared to placebo and inconsistency among studies (I²). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: Out of 3,926 retrieved records, 46 reports (49 studies) were included (n=20,337 participants). The most frequent clinical conditions included in the studies were osteoarthritis (n=21) and rheumatoid arthritis (n=8). Most studies assessed celecoxib (n=25), etoricoxib (n=17), and lumiracoxib (n=8). Coxibs increased the risk of edema (RR 1.46; 95% CI 1.15, 1.86; I² = 0%; 34 studies, 19,754 participants; moderate-certainty evidence), and celecoxib increased hypertensive or renal events (RR 1.24; 95% CI 1.08, 1.43; I² = 0%; 2 studies, 3589 participants; moderate-certainty evidence). Etoricoxib increased the risk of hypertension (RR 1.98; 95% CI 1.14, 3.46; I² = 34%; 13 studies, 6560 participants; moderate-certainty evidence); no difference was observed when pooling all coxibs (RR 1.26; 95% CI 0.91, 1.76; I² = 0%; 27 studies, 16,173 participants; moderate-certainty evidence). Glycosuria, hematuria and urinary retention were not affected by coxib use (moderate to very low-certainty evidence). Conclusion: Coxibs likely increase the incidence of renal adverse effects, including hypertension and edema. Awareness about the renal risks of coxibs should be increased, mainly in high-risk patient.
Relevance and importance to patients: Concerns about the safety of coxibs on cardiovascular and gastrointestinal is well known. Patients need to be aware of the renal risks of using these drugs, which can cause serious problems such as edema e hypertension even in the short-term use such as in randomized controlled trials.