环孢素联合糖皮质激素对比环磷酰胺联合糖皮质激素治疗膜性肾病有效性与安全性的Meta分析
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摘要
目的:系统评价环孢素联合糖皮质激素对比环磷酰胺联合糖皮质激素治疗膜性肾病的有效性与安全性。方法:计算机检索Embase、Medline、中国知网、维普中文科技期刊数据库、万方数据库,收集环孢素联合糖皮质激素(试验组)对比环磷酰胺联合糖皮质激素(对照组)治疗膜性肾病的随机对照试验(RCT),筛选文献、提取资料并采用Jadad量表评价文献质量后,采用Rev Man 5.3统计软件进行Meta分析。结果:共纳入6项RCT,共计312例患者。Meta分析结果显示,试验组患者治疗3个月后缓解率[OR=3.42,95%CI(2.05,5.71),P<0.000 01]、复发率[OR=3.12,95%CI(1.45,6.70),P=0.004]、治疗12个月后白细胞计数[MD=1.77,95%CI(0.96,2.58),P<0.000 1]均显著高于对照组;两组患者治疗6个月后缓解率[OR=2.06,95%CI(0.80,5.30),P=0.13]、治疗12个月后缓解率[OR=1.30,95%CI(0.68,2.48),P=0.42]、治疗3个月后血肌酐水平[MD=-1.55,95%CI(-6.72,3.62),P=0.56]、治疗6个月后血肌酐水平[MD=-1.21,95%CI(-5.96,3.54),P=0.62]、治疗12个月后胆固醇水平[MD=-0.77,95%CI(-1.81,0.28),P=0.15]、治疗12个月后丙氨酸转氨酶[MD=-0.40,95%CI(-4.38,3.58),P=0.98]比较,差异均无统计学意义。RCT报道了5项不良反应发生情况,但结果不一。结论:环孢素联合糖皮质激素治疗膜性肾病的远期有效性与环磷酰胺联合糖皮质激素相当,环孢素联合糖皮质激素起效更快,但复发率较高。
OBJECTIVE:To systematically evaluate the efficacy and safety of cyclosporin combined with glucocorticoid versus cyclophosphamide combined with glucocorticoid in the treatment of membranous nephropathy(MN). METHODS:Retrieved from Embase,Medline,CNKI,VIP and Wanfang database,RCTs about cyclosporin combined with glucocorticoid(trial group)versus cyclophosphamide combined with glucocorticoid(control group) in the treatment of MN were collected. Meta-analysis was conducted by using Rev Man 5.3 statistical software after literature screening,data extraction and quality evaluation with Jadad scale. RESULTS:Totally 6 RCTs were included,involving 312 patients in total. Results of Meta-analysis showed that remission rate 3 months after treatment [OR=3.42,95%CI(2.05,5.71),P<0.000 01] and relapse rate [OR=3.12,95%CI(1.45,6.70),P=0.004],leukocyte count 12 months after treatment [MD=1.77,95%CI(0.96,2.58),P<0.000 1] in trial group were significantly higher than control group. There was no statistical significance in remission rate 6 months after treatment [OR=2.06,95%CI(0.80,5.30),P=0.13] and remission rate 12 months after treatment[OR=1.30,95% CI(0.68,2.48),P=0.42],blood creatinine level 3 months after treatment [MD=-1.55,95%CI(-6.72,3.62),P=0.56] and blood creatinine level 6 months after treatment [MD=-1.21,95% CI(-5.96,3.54),P=0.62],cholesterol level 12 months after treatment [MD=-0.77,95%CI(-1.81,0.28),P=0.15] or ALT level[MD=-0.40,95%CI(-4.38,3.58),P=0.98] between 2 groups. ADR were reported in 5 RCTs,but their results were different. CONCLUSIONS:Long-term efficacy of cyclosporine combined with corticosteroid is similar to that of cyclophosphamide combined with corticosteroid in the treatment of MN. Cyclosporin combined with glucocorticoid has a faster effect,but a higher relapse rate.
OBJECTIVE:To systematically evaluate the efficacy and safety of cyclosporin combined with glucocorticoid versus cyclophosphamide combined with glucocorticoid in the treatment of membranous nephropathy(MN). METHODS:Retrieved from Embase,Medline,CNKI,VIP and Wanfang database,RCTs about cyclosporin combined with glucocorticoid(trial group)versus cyclophosphamide combined with glucocorticoid(control group) in the treatment of MN were collected. Meta-analysis was conducted by using Rev Man 5.3 statistical software after literature screening,data extraction and quality evaluation with Jadad scale. RESULTS:Totally 6 RCTs were included,involving 312 patients in total. Results of Meta-analysis showed that remission rate 3 months after treatment [OR=3.42,95%CI(2.05,5.71),P<0.000 01] and relapse rate [OR=3.12,95%CI(1.45,6.70),P=0.004],leukocyte count 12 months after treatment [MD=1.77,95%CI(0.96,2.58),P<0.000 1] in trial group were significantly higher than control group. There was no statistical significance in remission rate 6 months after treatment [OR=2.06,95%CI(0.80,5.30),P=0.13] and remission rate 12 months after treatment[OR=1.30,95% CI(0.68,2.48),P=0.42],blood creatinine level 3 months after treatment [MD=-1.55,95%CI(-6.72,3.62),P=0.56] and blood creatinine level 6 months after treatment [MD=-1.21,95% CI(-5.96,3.54),P=0.62],cholesterol level 12 months after treatment [MD=-0.77,95%CI(-1.81,0.28),P=0.15] or ALT level[MD=-0.40,95%CI(-4.38,3.58),P=0.98] between 2 groups. ADR were reported in 5 RCTs,but their results were different. CONCLUSIONS:Long-term efficacy of cyclosporine combined with corticosteroid is similar to that of cyclophosphamide combined with corticosteroid in the treatment of MN. Cyclosporin combined with glucocorticoid has a faster effect,but a higher relapse rate.
引文
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[4]SHA W,SHEN L,ZHOU L,et al.Silencing of CXCL12performs a protective effect on C5b-9-induced injury in podocytes[J].Int Urol Nephrol,2018,5(8):1535-1544.
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[6]刘晓霞,王琳.特发性膜性肾病发生的免疫机制及免疫抑制剂治疗研究进展[J].山东医药,2018,58(14):94-97.
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[8]伍秋霞,龚智峰.中小剂量环孢素治疗膜性肾病20例临床观察[J].中国药师,2011,14(1):115-117.
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[11]李鑫宇,赵学智.环孢素A与环磷酰胺治疗原发性膜性肾病疗效的对比观察[J].中国中西医结合肾病杂志,2011,12(10):906-908.
[12]解娟,郭王,张启东,等.环磷酰胺与环孢素A联合激素治疗膜性肾病的远期疗效观察[J].中国中西医结合肾病杂志,2014,15(8):716-719.
[13]陈忠锋,张建伟,夏楠楠,等.环孢素A与环磷酰胺联合激素治疗特发性膜性肾病的疗效比较[J].中国医药科学,2014.DOI:10.3969/j.issn.2095-0616.2014.16.005.
[14]LV Q,YANG F,CHEN K,et al.Autophagy protects podocytes from sublytic complement induced injury[J].Exp Cell Res,2016,341(2):132-138.
[15]HAYASHI N,OKADA K,MATSUI Y,et al.Glomerular mannose-binding lectin deposition in intrinsic antigen-related membranous nephropathy[J].Nephrol Dial Transplant,2017,33(5):832-840.
[16]刘书真,谢泉琨,党勇.环磷酰胺、来氟米特联合泼尼松序贯疗法用于Ⅱ期膜性肾病的临床观察[J].中国药房,2016,27(15):2040-2042.
[17]陈超阳,盛晓燕,周颖,等.他克莫司治疗原发性肾病综合征的疗效和安全性的Meta分析[J].中国新药杂志,2015,24(1):64-73.
[18]SCHIEPPATI A,PERNA A,ZAMORA J,et al.Immunosuppressive treat-ment for idiopathic membranous nephropathy in adults with nephrotic syndrome[J].Cochrane Database Syst Rev,2004,18(4):CDO04293.
[19]PONTICELLI C,ALTIERI P,SCOLARI F,et al.A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy[J].J Am Soc Nephrol,1998,9(3):444-450.
[20]常雄.他克莫司或来氟米特联合泼尼松治疗特发性膜性肾病的疗效及安全性对比[J].药物评价研究,2016,39(5):818-819.
[2]王海燕.肾小球肾炎临床实践指南[S].北京:人民卫生出版社,2013:105-145.
[3]CUSTóDIO FB,SILVA CAD,HELMO FR,et al.Complement system and C4d expression in cases of membranous nephropathy[J].J Bras Nefrol,2017,39(4):370-375.
[4]SHA W,SHEN L,ZHOU L,et al.Silencing of CXCL12performs a protective effect on C5b-9-induced injury in podocytes[J].Int Urol Nephrol,2018,5(8):1535-1544.
[5]LIU WJ,LI ZH,CHEN XC,et al.Blockage of the lysosome-dependent autophagic pathway contributes to complement membrane attack complex-induced podocyte injury in idiopathic membranous nephropathy[J].Sci Rep,2017.DOI:10.1038/s41598-017-07889-z.
[6]刘晓霞,王琳.特发性膜性肾病发生的免疫机制及免疫抑制剂治疗研究进展[J].山东医药,2018,58(14):94-97.
[7]JADAD AR,MOORE RA,CARROLL D,et al.Assessing the quality of reports of randomized clinical trials:is blinding necessary?[J].Control Clin trals,1996,17(1):1-12.
[8]伍秋霞,龚智峰.中小剂量环孢素治疗膜性肾病20例临床观察[J].中国药师,2011,14(1):115-117.
[9]张翔.小剂量环孢素A联合小剂量泼尼松治疗特发性膜性肾病的效果[J].中国医药指南,2013,11(30):121-122.
[10]刘继承,安自民,张立存,等.环孢素A联合激素治疗膜性肾病的疗效观察[J].齐齐哈尔医学院学报,2013,34(13):1910-1912.
[11]李鑫宇,赵学智.环孢素A与环磷酰胺治疗原发性膜性肾病疗效的对比观察[J].中国中西医结合肾病杂志,2011,12(10):906-908.
[12]解娟,郭王,张启东,等.环磷酰胺与环孢素A联合激素治疗膜性肾病的远期疗效观察[J].中国中西医结合肾病杂志,2014,15(8):716-719.
[13]陈忠锋,张建伟,夏楠楠,等.环孢素A与环磷酰胺联合激素治疗特发性膜性肾病的疗效比较[J].中国医药科学,2014.DOI:10.3969/j.issn.2095-0616.2014.16.005.
[14]LV Q,YANG F,CHEN K,et al.Autophagy protects podocytes from sublytic complement induced injury[J].Exp Cell Res,2016,341(2):132-138.
[15]HAYASHI N,OKADA K,MATSUI Y,et al.Glomerular mannose-binding lectin deposition in intrinsic antigen-related membranous nephropathy[J].Nephrol Dial Transplant,2017,33(5):832-840.
[16]刘书真,谢泉琨,党勇.环磷酰胺、来氟米特联合泼尼松序贯疗法用于Ⅱ期膜性肾病的临床观察[J].中国药房,2016,27(15):2040-2042.
[17]陈超阳,盛晓燕,周颖,等.他克莫司治疗原发性肾病综合征的疗效和安全性的Meta分析[J].中国新药杂志,2015,24(1):64-73.
[18]SCHIEPPATI A,PERNA A,ZAMORA J,et al.Immunosuppressive treat-ment for idiopathic membranous nephropathy in adults with nephrotic syndrome[J].Cochrane Database Syst Rev,2004,18(4):CDO04293.
[19]PONTICELLI C,ALTIERI P,SCOLARI F,et al.A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy[J].J Am Soc Nephrol,1998,9(3):444-450.
[20]常雄.他克莫司或来氟米特联合泼尼松治疗特发性膜性肾病的疗效及安全性对比[J].药物评价研究,2016,39(5):818-819.