Abstract: Background  The efficacy of endothelin receptor antagonists (ERA) in reducing proteinuria in patients with IgA nephropathy (IgAN) has been validated in phase III clinical trials. Ambrisentan, as a selective ERA receptor antagonist, protects the kidneys by antagonizing endothelin. Our study aimed to investigate the efficacy and safety of ambrisentan in patients with IgAN.  Methods  Medical records and follow-up data of IgAN patients treated with ambrisentan in our hospital from November 2022 to December 2023 were collected. Follow-up assessments were conducted at weeks 4, 8, and 12. The primary outcomes were 24-hour urinary protein, 24-hour urinary protein change rate estimated glomerular filtration rate (eGFR), and drug safety monitoring.  Results  A total of 147 IgAN patients were included in the study. The baseline 24h urinary protein level was 1.16 [0.74,1.99] g/day. Compared to baseline, the urinary protein level was 0.7 (0.38 to 1.32) g/day at week 4, with a reduction of 40.5%, Z=-8.157,P＜0.001. At week 8, the urinary protein level was 0.60 (0.43 to 1.44) g/day, with a reduction of 40.25%, Z=-5.866, P＜0.001. At week 12, the urinary protein level was 0.66 (0.43 to 1.43) g/day, with a reduction of 38.9%, Z=-5.238, P＜0.001.There was no significant difference in the rate of 24h UP reduction among subgroups stratified by gender, eGFR, or concomitant medication including steroids, immunosuppressants, and Renin-Angiotensin-Aldosterone System inhibitor (RAASi). eGFR remained stable during the 12-week follow-up period. Ambrisentan was well tolerated in the follow-up patients, with two patients discontinuing treatment due to edema or impaired liver function. Conclusion Ambrisentan can reduce proteinuria in patients with IgAN and is well tolerated.

Key words: Endothelin receptor antagonists; , IgA nephropathy, Proteinuria, Ambrisentan