(188) Renal outcomes of cyclooxygenase-2 inhibitor anti-inflammatories: a systematic review and meta-analysis

Background: Selective cyclooxygenase-2 inhibitor anti-inflammatory drugs (coxibs) are associated with the development of adverse events, mainly gastrointestinal and cardiovascular, but renal effects are less known.

Objectives: 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 (comprising 49 studies) were included, comprising 20,337 participants included in the studies. The most frequent clinical conditions reported 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 (RR 0.40; 95% CI 0.11, 1.46; 1 study, 372 participants; moderate-certainty evidence), hematuria (RR 1.81; 95% CI 0.60, 5.43; I² = 0%; 2 studies, 1133 participants; moderate-certainty evidence), and urinary retention (RR 0.96; 95% CI 0.13, 7.15; I² = 57%; 3 studies, 487 participants; very low-certainty evidence) were not affected by coxib use.

Conclusions: 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.