Abstract
BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Endothelin A receptor activation is a key driver of proteinuria, inflammation and fibrosis in IgAN. This systematic review and meta-analysis aimed to comprehensively evaluate the efficacy and safety of endothelin A receptor antagonists (EARAs) in IgAN patients. METHODS: PubMed, Embase, Web of Science and Cochrane Library were searched from inception to 31 October 2024. All randomized controlled trials were identified according to the inclusion criteria. Data were analyzed by RevMan 5.4. RESULTS: Four high-quality studies were included, comprising 1346 IgAN patients. Compared with the control group, EARAs group achieved a greater reduction in urine protein-creatinine ratio (UPCR) [mean difference (MD) -31.89, 95% confidence interval (CI) -37.50 to -26.28], systolic blood pressure (BP) (MD -2.78, 95% CI -4.11 to -1.44) and diastolic BP (MD -4.12, 95% CI -5.24 to -2.99), and a smaller reduction in estimated glomerular filtration rate (eGFR) (MD 4.10, 95% CI -0.76 to 8.96). However, the EARAs group had higher risk of anemia [odds ratio (OR) 2.38, 95% CI 1.54 to 3.69], cough (OR 2.27, 95% CI 1.24 to 4.15), dizziness (OR 2.37, 95% CI 1.51 to 3.71), hypotension (OR 2.39, 95% CI 1.56 to 3.67), fluid retention (OR 1.46, 95% CI 1.04 to 2.05) and acute kidney injury (OR 3.12, 95% CI 1.31 to 7.42). CONCLUSION: EARAs can significantly reduce UPCR, lower both systolic and diastolic BP, and delay eGFR decline in IgAN patients. However, they may cause anemia, cough, dizziness, hypotension, fluid retention and acute kidney injury.