Efficacy and safety of ambrisentan in IgA nephropathy: real-world evidence

Background Ambrisentan, an endothelin receptor antagonist, reduces proteinuria; however, insufficient evidence is available to support its use in IgAN. The aim of this research is to investigate the efficacy and safety of ambrisentan in the treatment of IgAN nephropathy. Methods This retrospective cohort study was enrolled 102 IgAN patients, which was confirmed by renal biopsy from Qilu Hospital, Shandong University (January 2021 to March 2026). 68 patients received ACEI/ARB treatment, while 34 IgAN patients received treatment with ACEI/ARB plus ambrisentan (5mg/day). The primary endpoint of the study assessed the percentage changes in UPCR in IgAN patients receiving different treatment regimens. Secondary endpoints included the change in eGFR and the safety of ambrisentan. Results 102 IgAN patients were enrolled in the research. ACEI/ARB + ambrisentan group exhibited higher rates of UPCR reduction compared with ACEI/ARB group: -35.9% [IQR, -46.7%, -12.2%] vs -11.8.0% [IQR, -35%, 3.19%] (P = 0.004) at 1 month, -52% [IQR, -61.6%, -26.6%] vs -22.4% [IQR, -42.5%, -2.8%] (P = 0.001) at 3 months, -43.1% [IQR, -61.3%, -27%] vs -29.8% [IQR, -52%, -0.2%] (P = 0.015) at 6 months. Furthermore, the UPCR was lower in the ACEI/ARB + ambrisentan group (0.45 g/g [IQR, 0.25, 0.85] vs 0.86 g/g [IQR, 0.52, 1.15]; P = 0.006) at 3 months, and (0.50 g/g [IQR, 0.37, 0.69] vs 0.85g/g [IQR, 0.51, 1.14]; P = 0.003) at 6 months. However, no statistically significant difference was observed between the two groups in terms of serum albumin levels. After treatment, the percentage change in eGFR from baseline was higher in the combination therapy group than in the ACEI/ARB group (1.6% vs -1.6%, p=0.014). At 6 months, the response rate in the ACEI/ARB + ambrisentan group was significantly higher (70.59% vs 48.53%, P = 0.034). Both groups experienced no serious adverse reactions. Conclusions The addition of ambrisentan to renin-angiotensin-aldosterone system (RAS) blockers significantly reduces urinary protein in IgAN patients, while remaining relatively safe.