吗替麦考酚酯诱导后长期维持治疗对增生性狼疮性肾炎预后的影响
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摘要
目的探讨激素联合吗替麦考酚酯(MMF)诱导后长期应用MMF维持治疗增生性狼疮性肾炎(LN)的疗效。方法回顾性分析2008年1月至2015年1月于咸阳市核工业215医院肾病科接受治疗的182例增生性LN患者的临床资料,所有患者均接受激素联合MMF诱导,获得缓解后,以接受激素、激素联合硫唑嘌呤或雷公藤多苷或来氟米特维持治疗者为C组,接受激素联合MMF维持治疗,且MMF维持时间≥18个月者为A组,接受激素联合MMF维持治疗,且MMF维持时间<18个月者为B组。观察患者诱导疗效,随访观察复发情况及复合肾脏终点事件发生情况。结果 182例患者中169例诱导进入缓解期,包括A组81例、B组58例、C组30例。诱导期MMF治疗6个月时,Ⅲ型、Ⅳ型患者缓解率分别为95.88%(31/32)、96.30%(104/108),明显好于Ⅳ+Ⅴ型患者的79.41%(27/34),差异均有统计学意义(P<0.05);54例患者复发,占31.95%,B、C组累积复发率分别为43.10%、40.00%,明显高于A组的20.99%,差异均有统计学意义(P<0.05),A组复发风险是C组的0.323倍(95%CI=0.152~0.687,P=0.003);复合肾脏终点事件共发生17例,B、C组累积肾脏复合事件发生率分别为13.79%、16.67%,明显高于A组的2.47%,差异均有统计学意义(P<0.05)。结论激素联合MMF诱导进入缓解期后,继续应用激素联合MMF维持治疗,能使LN患者持续获得较可靠的缓解率,且长期应用MMF有助于降低复发及复合肾脏终点时间发生率。
Objective To investigate the efficacy of long-term maintenance therapy on proliferative lupus nephritis(LN) after induction immunosuppression by mycophenolate mofetil(MMF). Methods The clinical data of 182 cases of proliferative LN, who admitted to Department of Nephrology of 215 Hospital of Nuclear Industry of Xianyang City from January 2008 to January 2015, were retrospectively analyzed. All cases received prednisolone and MMF as induction immunosuppression, then in catabasis. The patients treated with prednisolone, prednisolone combined with azathioprine or tripterygium glycosides or leflunomide for maintenance therapy were included into group C; the patients treated with prednisolone combined with MMF(≥18 months) were enrolled into group A; the patients treated with prednisolone combined with MMF(<18 months) were enrolled into group B. The curative effect during induction immunosuppression, the recurrence and the occurrence of compound renal endpoint events were observed. Results Among the182 patients, 169 cases were induced into remission stage, including 81 cases in group A, 58 cases in group B, and 30 cases in group C. At the induction phase, 6 months after MMF treatment, the remission rates of type Ⅲ and Ⅳ patients were 95.88%(31/32) and 96.30%(104/108), respectively, which were significantly better than 79.41%(27/34) of patients with type Ⅳ and Ⅴ(P<0.05). There were 54 relapses with the recurrence rate of 31.95%. The cumulative recurrence rates of group B and C were 43.10% and 40.00%, respectively, which were significantly higher than 20.99% of group A(P<0.05). The relapse risk in group A was 0.323 times that in group C(95%CI=0.152-0.687, P=0.003). A total of 17 cases of compound kidney endpoint events occurred. The incidences of cumulative renal complex events in group B and C were 13.79% and 16.67% respectively, which was significantly higher than 2.47% in group A(P<0.05).Conclusion After induction immunosuppression by prednisolone and MMF, long-term MMF maintenance therapy can lead to better sustained remission rate and help to reduce the relapse rate and the incidence rate of compound renal endpoint events.
Objective To investigate the efficacy of long-term maintenance therapy on proliferative lupus nephritis(LN) after induction immunosuppression by mycophenolate mofetil(MMF). Methods The clinical data of 182 cases of proliferative LN, who admitted to Department of Nephrology of 215 Hospital of Nuclear Industry of Xianyang City from January 2008 to January 2015, were retrospectively analyzed. All cases received prednisolone and MMF as induction immunosuppression, then in catabasis. The patients treated with prednisolone, prednisolone combined with azathioprine or tripterygium glycosides or leflunomide for maintenance therapy were included into group C; the patients treated with prednisolone combined with MMF(≥18 months) were enrolled into group A; the patients treated with prednisolone combined with MMF(<18 months) were enrolled into group B. The curative effect during induction immunosuppression, the recurrence and the occurrence of compound renal endpoint events were observed. Results Among the182 patients, 169 cases were induced into remission stage, including 81 cases in group A, 58 cases in group B, and 30 cases in group C. At the induction phase, 6 months after MMF treatment, the remission rates of type Ⅲ and Ⅳ patients were 95.88%(31/32) and 96.30%(104/108), respectively, which were significantly better than 79.41%(27/34) of patients with type Ⅳ and Ⅴ(P<0.05). There were 54 relapses with the recurrence rate of 31.95%. The cumulative recurrence rates of group B and C were 43.10% and 40.00%, respectively, which were significantly higher than 20.99% of group A(P<0.05). The relapse risk in group A was 0.323 times that in group C(95%CI=0.152-0.687, P=0.003). A total of 17 cases of compound kidney endpoint events occurred. The incidences of cumulative renal complex events in group B and C were 13.79% and 16.67% respectively, which was significantly higher than 2.47% in group A(P<0.05).Conclusion After induction immunosuppression by prednisolone and MMF, long-term MMF maintenance therapy can lead to better sustained remission rate and help to reduce the relapse rate and the incidence rate of compound renal endpoint events.
引文
[1]Mohan C,Putterman C.Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis[J].Nat Rev Nephrol,2015,11(6):329-341.
[2]许圣淳,刘正钊,章海涛,等.吗替麦考酚酯诱导治疗弥漫增生性狼疮性肾炎的临床疗效[J].肾脏病与透析肾移植杂志,2014,23(6):512-516,506.
[3]Lee YH,Song GG.Relative efficacy and safety of tacrolimus,mycophenolate mofetil,and cyclophosphamide as induction therapy for lupus nephritis:a Bayesian network meta-analysis of randomized controlled trials[J].Lupus,2015,24(14):1520-1528.
[4]Henderson LK,Masson P,Craig JC,et al.Induction and maintenance treatment of proliferative lupus nephritis:a meta-analysis of randomized controlled trials[J].Am J Kidney Dis,2013,61(1):74-87.
[5]中华医学会风湿病学分会.系统性红斑狼疮诊断及治疗指南[S].中华风湿病学杂志,2010,14(5):342-346.
[6]Weening JJ,D'Agati VD,Schwartz MM,et al.The classification of glomerulonephritis in systemic lupus erythematosus revisited[J].Kidney Int,2004,65(2):521-430.
[7]程莹,李宁娜,游志清,等.三种CKD-EPI公式与改良MDRD公式诊断糖尿病肾病一致性分析[J].中国全科医学,2016,19(29):3584-3588.
[8]刘倩,张晶,卢克鹏,等.吗替麦考酚酯对比环磷酰胺治疗狼疮性肾炎的有效性和安全性的系统评价[J].中国药房,2014,25(36):3387-3391.
[9]章丽和,陈晓微,陈阿琼,等.糖皮质激素联合环磷酰胺和来氟米特治疗狼疮性肾炎的临床研究[J].医学研究杂志,2013,42(4):139-144.
[10]Kurasawa T,Nagasawa H,Nishi E,et al.Successful treatment of class IV+V lupus nephritis with combination therapy of high-dose corticosteroids,tacrolimus and intravenous cyclophosphamide[J].Intern Med,2013,52(10):1125-1130.
[11]Yap DY,Ma MK,Mok MM,et al.Long-term data on corticosteroids and mycophenolate mofetil treatment in lupus nephritis[J].Rheumatology(Oxford),2013,52(3):480-486.
[12]Laskari K,Tzioufas AG,Antoniou A,et al.Longterm followup after tapering mycophenolate mofetil during maintenance treatment for proliferative lupus nephritis[J].J Rheumatol,2011,38(7):1304-1308.
[13]Tamirou F,D'Cruz D,Sangle S,et al.Long-term follow-up of the MAINTAIN Nephritis Trial,comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis[J].Ann Rheum Dis,2016,75(3):526-531.
[14]Mejía-Vilet JM,Córdova-Sánchez BM,Arreola-Guerra JM,et al.Renal flare prediction and prognosis in lupus nephritis Hispanic patients[J].Lupus,2016,25(3):315-324.
[2]许圣淳,刘正钊,章海涛,等.吗替麦考酚酯诱导治疗弥漫增生性狼疮性肾炎的临床疗效[J].肾脏病与透析肾移植杂志,2014,23(6):512-516,506.
[3]Lee YH,Song GG.Relative efficacy and safety of tacrolimus,mycophenolate mofetil,and cyclophosphamide as induction therapy for lupus nephritis:a Bayesian network meta-analysis of randomized controlled trials[J].Lupus,2015,24(14):1520-1528.
[4]Henderson LK,Masson P,Craig JC,et al.Induction and maintenance treatment of proliferative lupus nephritis:a meta-analysis of randomized controlled trials[J].Am J Kidney Dis,2013,61(1):74-87.
[5]中华医学会风湿病学分会.系统性红斑狼疮诊断及治疗指南[S].中华风湿病学杂志,2010,14(5):342-346.
[6]Weening JJ,D'Agati VD,Schwartz MM,et al.The classification of glomerulonephritis in systemic lupus erythematosus revisited[J].Kidney Int,2004,65(2):521-430.
[7]程莹,李宁娜,游志清,等.三种CKD-EPI公式与改良MDRD公式诊断糖尿病肾病一致性分析[J].中国全科医学,2016,19(29):3584-3588.
[8]刘倩,张晶,卢克鹏,等.吗替麦考酚酯对比环磷酰胺治疗狼疮性肾炎的有效性和安全性的系统评价[J].中国药房,2014,25(36):3387-3391.
[9]章丽和,陈晓微,陈阿琼,等.糖皮质激素联合环磷酰胺和来氟米特治疗狼疮性肾炎的临床研究[J].医学研究杂志,2013,42(4):139-144.
[10]Kurasawa T,Nagasawa H,Nishi E,et al.Successful treatment of class IV+V lupus nephritis with combination therapy of high-dose corticosteroids,tacrolimus and intravenous cyclophosphamide[J].Intern Med,2013,52(10):1125-1130.
[11]Yap DY,Ma MK,Mok MM,et al.Long-term data on corticosteroids and mycophenolate mofetil treatment in lupus nephritis[J].Rheumatology(Oxford),2013,52(3):480-486.
[12]Laskari K,Tzioufas AG,Antoniou A,et al.Longterm followup after tapering mycophenolate mofetil during maintenance treatment for proliferative lupus nephritis[J].J Rheumatol,2011,38(7):1304-1308.
[13]Tamirou F,D'Cruz D,Sangle S,et al.Long-term follow-up of the MAINTAIN Nephritis Trial,comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis[J].Ann Rheum Dis,2016,75(3):526-531.
[14]Mejía-Vilet JM,Córdova-Sánchez BM,Arreola-Guerra JM,et al.Renal flare prediction and prognosis in lupus nephritis Hispanic patients[J].Lupus,2016,25(3):315-324.