摘要
目的比较无激素方案[小剂量利妥昔单抗(RTX)联合小剂量他克莫司(TAC)]与经典含激素方案[泼尼松联合他克莫司(TAC)]治疗初发型原发性膜性肾病(PMN)患者的疗效和安全性。方法选择2021年8月至2022年2月在新乡医学院第一附属医院肾脏病医院就诊的成人PMN患者为研究对象。将患者随机分为观察组(n=32)和对照组(n=32),观察组患者给予小剂量RTX联合小剂量TAC治疗,对照组患者给予泼尼松联合TAC治疗。2组患者均连续治疗6个月,治疗后评估2组患者的临床疗效,并计算总有效率,同时评估2组患者的血清学缓解率。分别于治疗前和治疗1、3、6个月检测2组患者的抗磷脂酶A2受体(PLA2R)抗体滴度、24小时尿蛋白定量(24 h UTP)、血肌酐(Scr)、估算的肾小球滤过率(eGFR)、白蛋白(Alb)水平,比较2组患者治疗前、治疗6个月CD19+B淋巴细胞计数,比较2组患者治疗1、3、6个月TAC血药浓度,观察2组患者治疗期间的不良反应。结果治疗1、3个月,2组患者总有效率比较差异无统计学意义(χ^(2)=1.180、1.277,P>0.05);治疗6个月,观察组患者总有效率显著高于对照组(χ^(2)=5.358,P<0.05)。治疗1个月,2组患者均无完全缓解;治疗3、6个月,2组完全缓解率比较差异无统计学意义(χ^(2)=0.592、0.043,P>0.05)。治疗1、3个月,2组患者部分缓解率比较差异无统计学意义(χ^(2)=1.180、2.944,P>0.05);治疗6个月,观察组患者部分缓解率显著高于对照组(χ^(2)=5.119,P<0.05)。治疗6个月,观察组患者血清学缓解率显著高于对照组(χ^(2)=14.618,P<0.05)。治疗前,2组患者PLA2R抗体滴度、24 h UTP、Scr、eGFR、Alb比较差异均无统计学意义(P>0.05)。治疗6个月,观察组患者抗PLA2R抗体滴度显著低于对照组(Z=-4.086,P<0.05)。治疗6个月,观察组及对照组患者24 h UTP均较治疗前显著下降(t=12.421、8.935,P<0.05);治疗1、3、6个月,2组患者24 h UTP、Scr、eGFR比较差异无统计学意义(P>0.05)。治疗6个月,2组患者Alb水平较治疗前均显著升高(t=-10.342、-7.374,P<0.05)。治疗3个月,观察组患者Alb水平显著低于对照组(t=-2.076,P<0.05);治疗1、6个月,2组患者Alb水平比较差异无统计学意义(t=-0.278、0.415,P>0.05)。治疗1、3、6个月,观察组患者TAC血药浓度均显著低于对照组(P<0.05)。至随访结束,观察组患者有2例发生输液反应,对照组患者未观察到明确不良反应。结论小剂量RTX联合小剂量TAC的无激素方案诱导PMN患者达到临床缓解及血清学缓解早于泼尼松联合TAC的经典方案,2组治疗方案不良反应均较少。
Objective To compare the efficacy and safety of hormone-free[low-dose rituximab(RTX)combined with low-dose tacrolimus(TAC)]and classical hormone-containing regimens[prednisone(P)combined with TAC]in the treatment of patients with primary membranous nephropathy(PMN).Methods Adult PMN patients who visited the Nephrology Hospital of the First Affiliated Hospital of Xinxiang Medical University from August 2021 to February 2022 were selected and randomly divided into an observation group(n=32)and a control group(n=32).Patients in the observation group were given low-dose RTX combined with low-dose TAC,and those in the control group were given P combined with TAC.Both groups of patients were treated for consecutive 6 months.After treatment,the clinical efficacy was evaluated,the total effective rate was calculated,and the serological response rate was evaluated.Phospholipase A2 receptor(PLA2R),24 hour urinary protein quantitative(24 h UTP),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),and albumin(Alb)levels were tested in two groups of patients before treatment,1,3 and 6 months after treatment.The CD19+B cell counts of the two groups of patients were compared before treatment and 6 months after treatment.The TAC blood concentrations in the two groups of patients were compared 1,3 and 6 months after treatment,and their adverse reactions during treatment were observed.Results After treatment for 1 and 3 months,the total effective rates of the two groups were not significantly different(χ^(2)=1.180,1.277,P>0.05).After treatment for 6 months,the total effective rate in the observation group was significantly higher than that in the control group(χ^(2)=5.358,P<0.05).After 1 month of treatment,both groups did not achieve complete remission.After 3 or 6 months of treatment,there was no statistically significant difference in complete remission rate between the two groups(χ^(2)=0.592,0.043;P>0.05).After treatment for 1 and 3 months,the partial response rates of the two groups were not significantly different(χ^(2)=1.180,2.944;P>0.05).After treatment for 6 months,the partial response rate in the observation group was significantly higher than that in the control group(χ^(2)=5.119,P<0.05).After treatment for 6 months,the serological response rate in the observation group was significantly higher than that in the control group(χ^(2)=14.618,P<0.05).There was no statistically significant difference in PLA2R,24 h UTP,Scr,eGFR,and Alb levels between the two groups(P>0.05).After 6 months of treatment,the PLA2R level of the observation group was significantly lower than that of the control group(Z=-4.086,P<0.05).The 24 h UTP levels after 6 months of treatment decreased significantly in both observation and control groups,compared with those before treatment(t=12.421,8.935;P<0.05).There was no statistically significant difference in 24 h UTP,Scr,and eGFR levels between the two groups after 1,3,and 6 months of treatment(P>0.05).The Alb levels after 6 months of treatment were significantly higher than those before treatment in both groups(t=-10.342,-7.374;P<0.05).After 3 months of treatment,the Alb levels in the observation group were significantly lower than those in the control group(t=-2.076,P<0.05).There was no statistically significant difference in Alb levels between the two groups after 1 and 6 months of treatment(t=-0.278,0.415;P>0.05).After 1,3 and 6 months of treatment,the TAC blood concentration in the observation group was significantly lower than that in the control group(P<0.05).By the end of the follow-up period,two patients in the observation group had infusion reactions,while no clear adverse reactions were observed in the control group.Conclusion The hormone-free regimen of low-dose RTX combined with low-dose TAC induces clinical and serological remission in PMN patients earlier than the classical regimen of P combined with TAC.Both treatment regimens cause few adverse reactions.
作者
邢晖林
马东红
李瑾
许清玉
姬利珂
朱琼杰
郭明好
XING Huilin;MA Donghong;LI Jin;XU Qingyu;JI Like;ZHU Qiongjie;GUO Minghao(Department of Nephrology,Nephrology Hospital,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China)
出处
《新乡医学院学报》
2025年第6期513-518,共6页
Journal of Xinxiang Medical University
基金
河南省医学科技攻关计划省部共建项目(编号:SB201901058)。
作者简介
邢晖林(1996-),女,河南卫辉人,硕士研究生在读,住院医师,研究方向:膜性肾病;通信作者:郭明好(1964-),男,河南封丘人,硕士,主任医师,研究方向:膜性肾病,E-mail:guomh@163.com。
