Efeitos renais dos anti-inflamatórios inibidores seletivos da Cicloxigenase-2: revisão sistemática e meta-análise

Abstract

Introduction: Selective cyclooxygenase-2 (COX-2) inhibitors are widely prescribed for their anti-inflammatory properties but have been associated with serious adverse events such as gastrointestinal bleeding and cardiovascular events, as documented in the literature [1]. Renal adverse events, though less frequently reported [2], pose significant risks including potential permanent damage and impact on patient quality of life. Therefore, a systematic review and meta-analysis are crucial to comprehensively evaluate these renal effects. Material and Methods: This systematic review and meta-analysis followed a protocol registered in PROSPERO (CRD42022380227). Randomized clinical trials assessing the renal effects of COX-2 inhibitors (celecoxib, etoricoxib, lumiracoxib, parecoxib, and valdecoxib) compared to placebo were eligible for inclusion. Search strategies using keywords such as 'cox 2 inhibitor', 'coxib', 'kidney', 'renal', 'tolerability', and 'safety' were applied to PubMed, Embase, CENTRAL, Scopus, and Web of Science in September 2022. Data extraction and quality assessment were conducted independently by two reviewers using the Covidence platform. Meta-analyses were performed in RevMan 5.4 using the Mantel-Haenszel random-effects model to calculate pooled risk ratios (RR) and 95% confidence intervals (CI) for renal outcomes, with heterogeneity assessed using I². The certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach as high, moderate, low, or very low. Results: A total of 3,926 articles were identified, and after screening, 46 articles (comprising 50 studies) were included for analysis. Celecoxib increased the risk of hypertensive or renal events (RR 1.24; 95% CI 1.07 to 1.43; I² 7%; 2 studies, 3,589 participants; moderate certainty). Etoricoxib increased the risk of hypertension (RR 1.98; 95% CI 1.14 to 3.46; I² 34%; 13 studies, 6,560 participants; low certainty), but no significant difference was observed when pooling all COX-2 inhibitors (RR 1.26; 95% CI 0.91 to 1.76; I² 25%; 27 studies, 16,174 participants; moderate certainty). COX-2 inhibitors increased the risk of edema (RR 1.48; 95% CI 1.17 to 1.87; I² 0%; 35 studies, 21,332 participants; low certainty). Creatinine levels (RR 0.73; 95% CI 0.21 to 2.55; I² 39%; 4 studies, 3,195 participants; very low certainty), glucosuria (RR 0.40; 95% CI 0.11 to 1.46; 1 study, 372 participants; low certainty), hematuria (RR 1.81; 95% CI 0.60 to 5.43; I² 0%; 2 studies, 1,133 participants; low certainty), and urinary retention (RR 0.99; 95% CI 0.13 to 7.55; I² 58%; 3 studies, 476 participants; very low certainty) were not significantly affected by COX-2 inhibitor use. Discussion and Conclusions: The findings indicate that selective COX-2 inhibitors are associated with an increased risk of renal adverse events, including hypertension and edema. Awareness of these renal risks associated with these medications should be heightened, guiding clinical practice and patient management strategies. Further research is warranted to strengthen the evidence and refine risk mitigation strategies for patients receiving COX-2 inhibitors.