安立生坦治疗IgA肾病的疗效及安全性分析

Efficacy and safety analysis of ambrisentan treatment for IgA nephropathy

目的探讨安立生坦作为选择性内皮素受体拮抗剂(endothelin receptor antagonist,ERA)在IgA肾病(IgA nephropathy,IgAN)患者中的疗效和安全性。方法收集北京大学第一医院肾内科2022年11月─2023年12月接受安立生坦治疗的IgA肾病患者的病历资料和随访数据,并在第4、8和12w时进行随访评估。研究的主要结果是随时间变化的24h尿蛋白、24h尿蛋白变化率、估算肾小球滤过率(estimate glomerular filtration rate,eGFR),同时监测药物的安全性。结果共纳入了147例IgA肾病患者。基线24h尿蛋白水平为1.16(0.74,1.99)g/d,安立生坦治疗后第4、第8、第12w的尿蛋白水平分别低于基线水平(Z=-8.157、-5.866、-5.238,均P<0.001)。在不同性别、eGFR分组、合并用药包括激素、免疫抑制剂、肾素-血管紧张素-醛固酮系统抑制剂(renin-angiotensin-aldosterone system inhibitor,RAASi)等亚组中,24h尿蛋白下降率无统计学差异(均P>0.05)。在12w随访期间,eGFR保持稳定。安立生坦在随访患者中耐受性良好,2例患者因水肿或肝功能损害停药。结论安立生坦可以降低IgA肾病患者尿蛋白且安全性良好。

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.