羟氯喹治疗IgA肾病疗效与安全性的单中心回顾性分析

Efficacy and safety of hydroxychloroquine in the treatment of IgA nephropathy:a single⁃center retrospective analysis

目的评价羟氯喹(hydroxychloroquine,HCQ)治疗IgA肾病(IgA nephropathy,IgAN)的疗效与安全性。方法回顾性分析2016年5月至2020年8月于浙江大学医学院附属第一医院行肾活检确诊、应用羟氯喹6个月以上且无其他免疫抑制剂治疗的IgAN患者资料,并根据基线尿蛋白/肌酐比值(UPCR)水平、是否联用肾素⁃血管紧张素⁃醛固酮系统阻滞剂(RAASi)分组,比较疗效与不良反应。结果共纳入121例患者,其中男性45例(37.19%);基线时中位UPCR为0.69(0.45,1.00)g/g,中位估算肾小球滤过率(eGFR)为93.46(73.14,115.67)ml·min^(-1)·(1.73 m^(2))-1,中位血清肌酐为80.00(61.00,98.00)μmol/L,血清白蛋白为(44.39±3.36)g/L。羟氯喹治疗后,IgAN患者UPCR和尿红细胞均较基线时显著下降(均P<0.05),三酰甘油、总胆固醇及低密度脂蛋白胆固醇在随访期间也明显下降,血清肌酐、eGFR、血清白蛋白、血清尿酸保持稳定。随访6个月时,总缓解率为56.88%,其中部分缓解率为15.60%,完全缓解率为41.28%;随访末期时中位随访280.00(214.00,411.00)d,总缓解率为56.20%,其中部分缓解率为9.92%,完全缓解率为46.28%。组间分析显示,6个月时基线UPCR<1 g/g组和≥1 g/g组的缓解率分别为60.53%(n=76)和48.48%(n=33)(Mann⁃Whitney U检验,Z=-2.331,P=0.020),随访末期的缓解率分别为57.65%(n=85)和52.78%(n=36)(Mann⁃Whitney U检验,Z=-1.673,P=0.094);单用羟氯喹组和羟氯喹+RAASi组的6个月缓解率分别为66.67%(n=30)和53.16%(n=79)(Mann⁃Whitney U检验,Z=1.062,P=0.288),随访末期的缓解率分别为61.29%(n=31)和54.44%(n=90)(Mann⁃Whitney U检验,Z=0.930,P=0.352)。不良反应上,2例患者eGFR较基线降低超过30%,1例复发,1例视物模糊。结论羟氯喹可用于治疗IgAN患者,安全性较好。

Objective To access the clinical efficacy and safety of hydroxychloroquine(HCQ)in treatment of IgA nephropathy(IgAN).Methods The data of IgAN patients who were diagnosed by renal biopsy in the First Affiliated Hospital,College of Medicine,Zhejiang University from May 2016 to August 2020 and had been treated with HCQ for more than 6 months without other immunosuppressants were retrospectively analyzed.The efficacy and side effects were compared between groups according to the baseline urine protein/creatinine ratio(UPCR)or whether combined with renin⁃angiotensin⁃aldosterone system inhibitor(RAASi).Results A total of 121 patients were enrolled,including 45 males(37.19%).At baseline,the median UPCR was 0.69(0.45,1.00)g/g;the median estimated glomerular filtration rate(eGFR)was 93.46(73.14,115.67)ml·min^(-1)·(1.73 m^(2))-1;the median serum creatinine was 80.00(61.00,98.00)μmol/L,and the serum albumin was(44.39±3.36)g/L.After HCQ treatment,UPCR and red blood cells were significantly decreased compared with baseline(all P<0.05).Triglyceride,total cholesterol and low⁃density lipoprotein cholesterol were also significantly decreased during the follow⁃up period.Serum creatinine,eGFR,serum albumin and serum uric acid remained stable.After 6 months of follow⁃up,the total remission rate was 56.88%,including 15.60%of partial remission and 41.28%of complete remission;at the end of follow⁃up,the median follow⁃up time was 280.00(214.00,411.00)days and the total remission rate was 56.20%,including 9.92%of partial remission and 46.28%of complete remission.Group analysis showed that the remission rate was 60.53%(n=76)and 48.48%(n=33)at 6 months(Mann⁃Whitney U test,Z=-2.331,P=0.020)and 57.65%(n=85)and 52.78%(n=36)at the end of follow⁃up(Mann⁃Whitney U test,Z=-1.673,P=0.094)between patients with baseline UPCR<1 g/g and patients with baseline UPCR≥1 g/g;and the remission rate was 66.67%(n=30)and 53.16%(n=79)at 6 months(Mann⁃Whitney U test,Z=1.062,P=0.288)and 61.29%(n=31)and 54.44%(n=90)at the end of follow⁃up(Mann⁃Whitney U test,Z=0.930,P=0.352)between patients with single HCQ and patients with HCQ+RAASi.For side effects,the eGFR of 2 patients decreased by more than 30%compared with baseline,1 patient relapsed and 1 patient developed blurred vision.Conclusions HCQ is safe and effective for the treatment of IgAN.