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Efficacy and Prognosis of Calcineurin inhibitors and Cyclophosphamide in Treating Idiopathic Membranous Nephropathy in Patients with Type 2 Diabetes
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摘要:
目的 比较不同初始治疗方案对2型糖尿病患者中特发性膜性肾病(idiopathic membranous nephropathy,IMN)的疗效及预后。 方法 回顾性收集并分析2004年1月至2015年4月在北京协和医院确诊的2型糖尿病合并IMN患者临床资料。根据初始治疗方案将患者分为环磷酰胺(cyclophosphamide,CTX)组、钙调磷酸酶抑制剂(calcineurin inhibitors,CNIs)组和其他治疗组。采用Kaplan-Meier生存分析和Cox多因素回归分析,观察不同治疗方案对患者总体缓解 (total remission,TR)率、完全缓解 (complete remission,CR)率、估算肾小球滤过率 (estimated glomerular filtration rate,eGFR)下降 ≥ 30%或进入终末期肾病 (end-stage renal disease,ESRD)、空腹血糖>8 mmol/L的影响。 结果 共纳入89例符合入选和排除标准的2型糖尿病合并IMN患者。多因素回归分析显示,CNIs组和CTX组在CR(HR=0.793,95% CI:0.315~1.999,P=0.623)、TR (HR=0.647,95% CI:0.334~1.252,P=0.196) 及空腹血糖>8 mmol/L(HR=1.709,95% CI:0.669~4.369,P=0.263)方面均无统计学差异。但CNIs组出现eGFR下降 ≥ 30%或进入ESRD的风险显著高于CTX组(HR=13.505,95% CI:1.512~120.665,P=0.020)。 结论 在2型糖尿病合并IMN患者中,CNIs与CTX作为初始治疗蛋白尿缓解率相当,但CNIs治疗后肾功能下降的风险显著增加。对此类患者需谨慎选择初始治疗方案。 Abstract:Objective The aim of this study was to compare the efficacy and prognosis of different therapeutic regimens in treating idiopathic membranous nephropathy (IMN) in patients with type 2 diabetes. Methods The clinical data were retrospectively collected and analyzed in patients with IMN and type 2 diabetes admitted in the Peking Union Medical College Hospital from January 2004 to April 2015. The patients were classified into three groups and designated as cyclophosphamide (CTX), calcineurin inhibitors (CNIs)and other immunosuppressants groups according to the initial therapeutic regimens. Kaplan-Meier analysis and multivariable Cox regression were used to assess the influence of therapeutic regimens on total remission (TR), complete remission (CR), risks of developing ≥ 30% decline in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD), and risks of achieving fast blood glucose >8 mmol/L. Results Totally, 89 patients meeting the inclusive and exclusive criteria were included in this study. The multivariable Cox analysis showed that patients initially treated with CNIs would be significantly higher to develop ≥ 30% eGFR decline or ESRD (HR=13.505, 95% CI:1.512-120.665, P=0.020) than those treated with CTX. However, the likeliness to reach CR(HR=0.793, 95% CI:0.315-1.999, P=0.623), TR(HR=0.647, 95% CI:0.334-1.252, P=0.196), or fast blood glucose >8 mmol/L (HR=1.709, 95% CI:0.669-4.369, P=0.263) were similar between the two groups. Conclusions In patients with type 2 diabetes, CNIs as the initial treatment for IMN might have comparable remission rate of proteinuria with CTX, but an extra risk of renal function decline. We would better be cautious in choosing the therapeutic regimens to treat IMN in patients with type 2 diabetes. 利益冲突 无 -
表 1 89例2型糖尿病合并特发性膜性肾病患者的一般临床资料
指标 CTX组(n＝22) CNIs组(n＝48) 其他治疗组(n＝19) P值 男性[n(%)] 16(72.7) 29(60.4) 10(52.6) 0.401 年龄(x±s, 岁) 56.0±8.9 58.5±10.9 56.4±10.7 0.596 体质量指数(x±s, kg/ m 2) 28.0±3.8 27.2±3.7 26.7±2.9 0.535 高血压[n (%)] 21(95.5) 37(77.1) 16(84.2) 0.161 肾病综合征[n (%)] 17 (77.3) 38 (79.2) 5 (26.3)*# ＜0.001 血清白蛋白(x±s, g/ L) 24.9±5.7 24.9±5.4 29.9±7.5*# 0.009 24 h尿蛋白量[M(P25, P75), g] 8.2 (5.1, 11.9) 8.4 (5.7, 12.4) 4.0 (1.2, 6.2)*# ＜0.001 eGFR [x±s, ml/(min.1.73 m 2)] 85.9±28.3 90.9±18. 6 100.0±12.7 0.109 慢性肾脏病分期[n(%)] 0.037 1期 14(66.7) 29(60.4) 16(88.9) 2期 2(9.5) 15(31.3) 2(11.1) 3期 4(19.0) 4(8.3) 0(0) 4期 1(4.8) 0(0) 0(0) 糖尿病病程[M(P25, P75), 月] 1.2(0.4, 24.7) 28.6(7.3, 121.6)* 32.7(2.8, 63.2)* 0.004 空腹血糖(x±s, mmol/L) 6.6±1.6 6.5±1.6 6.4±1.0 0.880 RASi治疗[n(%)] 18(81.8) 42(87.5) 18(94.7) 0.569 糖皮质激素治疗 接受的患者比例[n(%)] 22(100.0) 31(64.6)* 7(36.8)*# ＜0.001 总剂量[M(P25, P75), g/kg] 0.18 (0.13, 0.26) 0.06 (0, 0.17)* 0 (0, 0.07)*# ＜0.001 初始剂量[M(P25, P75), mg/(kg.d)] 0.80(0.70, 0.91) 0.40(0.36, 0.47)* 0.32(0.25, 0.40)* ＜0.001 总疗程[M(P25, P75), 月] 19.5(9.7, 26.5) 17.6(10.9, 23.1) 20.3(14.0, 21.2) 0.868 随访时间[M(P25, P75).年] 2.5(1.7, 3.9) 3.0(1.3, 5.2) 3.4(0.5, 4.3) 0.692 与CTX组比较, *P＜0.01;与CNIs组比较, #P＜0.01;CTX:环磷酰胺;CNIs: 钙调磷酸酶抑制剂; eGFR: 估算肾小球滤过率; RASi: 肾素-血管 紧张素系统抑制剂 
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表 2 89例2型糖尿病合并特发性膜性肾病患者初始治疗方案与蛋白尿缓解的相关性
蛋白尿终点事件 HR(95% CI) P值 总体缓解 钙调磷酸酶抑制剂组比环磷酰胺组 0. 647 (0. 334~1. 252) 0. 196 其他治疗组比环磷酰胺组 0. 438 (0. 141~1. 361) 0. 154 钙调磷酸酶抑制剂组比其他治疗组 3. 319 (0. 702~15. 686) 0. 130 完全缓解 钙调磷酸酶抑制剂组比环磷酰胺组 0. 793 (0. 315~1. 999) 0. 623 其他治疗组比环磷酰胺组 0. 239 (0. 039~1. 453) 0. 120 钙调磷酸酶抑制剂组比其他治疗组 1. 478 (0. 584~3. 738) 0. 409
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