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 selec-tive 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 collect-ed.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 moni-toring.Results A total of 147 IgAN patients were included in the study.The baseline 24h urinary protein lev-el 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 re-mained 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.
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