特发性膜性肾病儿童35例的治疗

Treatment of idiopathic membranous nephropathy in 35 children

目的观察特发性膜性肾病（IMN）患儿糖皮质激素及免疫抑制剂治疗疗效及转归。方法回顾性调查研究2004年3月至2013年7月住院经病理证实为膜性肾病且临床未发现继发因素、达肾病水平蛋白尿的患儿35例，观察糖皮质激素及免疫抑制剂治疗疗效及转归。结果35例IMN患儿包括男18例，女17例，男女之比1．1：1．0；起病年龄3．0—17．1岁（11．3±0．5）岁；24例有镜下血尿，5例伴肉眼血尿，8例伴高血压，1例慢性肾功能不全，2例并发血栓。病理I期、Ⅱ期、Ⅲ期的比例分别为25．7％（9／35例）、45．7％（16／35例）、28．6％（10／35例）；94．3％（33／35例）伴不同程度系膜细胞及基质增生。均首选糖皮质激素治疗，34例激素耐药，1例激素敏感，复发后激素耐药。17例应用环孢素（CsA）治疗并达3个月以上，用药后13例完全缓解，3例部分缓解，1例未缓解，完全缓解率76．5％（13／17例），总有效率93．8％（16／17例），尿蛋白阴转时间平均（4．9±3．7）个月；5例应用霉酚酸酯（MMF）治疗，4例分别于用药后2个月、4个月、5个月、9个月完全缓解，1例部分缓解；6例应用环磷酰胺（CTX）治疗，累积量（91．2±46．5）mg／kg，1例完全缓解（87mg／kg），1例部分缓解（160ms／kg），4例未缓解。1例应用利妥昔单抗（RTX）完全缓解。1例应用来氟米特（LEF）部分缓解。糖皮质激素联合CsA治疗完全缓解率优于单纯糖皮质激素治疗（76．5％比12．5％，P=0．004），有效率差异无统计学意义（94．2％比62．5％，P=0．081）。糖皮质激素联合CsA治疗完全缓解率（76．5％比38．5％，P=0．042）及有效率（94．1％比61．5％，P=0．040）均优于糖皮质激素联合其他免疫抑制剂，其完全缓解率及有效率亦优于CTX（76．5％比16．7％，P=0．018；94．1％比33．3％，P=0．008）。而CsA治疗与MMF比较，完全缓解率及有效率差异均无统计学意义（76．5％比80．O％，P=0．687；94．1％比100．0％，P=0．773）。结论IMN多有激素耐药，CsA治疗疗效肯定，优于传统免疫抑制剂CTX，而MMF的作用值得重视，其疗效并不逊于CsA。

Objective To investigate the prognosis and efficiency of glucocorticoid and immunosuppressor in the treatment of idiopathic membranous nephropathy（IMN） in children. Methods A retrospective analysis of 35 cases of biopsy - proven membranous nephropathy without secondary factors was performed, who were found present with ne- phrotic proteinuria and admitted to hospital from March 2004 to July 2013, to explore the efficiency of treatment with glucocorticoid and immunosuppressor and its prognosis. Results The 35 IMN cases included 18 boys and 17 girls, and the ratio was 1. 1 ： 1. 0. The mean age at onset was （ 11. 3 ± 0. 5 ） years with a range of 3.0 - 17. l years. Five cases with gross hematuria,24 cases present with microscopic hematuria,8 cases with hypertension, I case with chronic renal insufficiency, and 2 cases were complicated with thrombosis. According to membranous nephropathy staging criteria, 9 cases（25.7% ） were in stage I , 16 cases（ 45.7% ） in stage Ⅱ , 10 cases （28.6%）in stage Ⅲ;about 94.3% （33/35 cases） had mesangial cells and mesangial matrix with mild to moderate hyperplasia. They were all treated with glucocor- ticoid initially and one of them showed sensitive to flucocorticoid but developed flucocorticoid resistance after relapse, while all the others were flucocorticoid - resistant. Cyclophosphamide A（CsA） was introduced to 17 cases and at least lasted for 3 months, in which 13 cases （76. 5% ） reached complete remission and 3 cases reached partial remission, while 1 case didn＇t achieve remission, and the mean time for proteinuria to disappear was （4.9 ± 3.7） months ;5 cases were treated with Mycophenolate mefetil （MMF）, among which 4 cases reached complete remission in 2 months, 4 months,5 months, and 9 months separately, while 1 case reached partial remission. Cyclophosphamide （CTX） was intro- duced to 6 cases,in which the mean cumulative dosage was （91.2 ± 46.5 ） mg/kg, among them 1 case （87 mg/kg） reached complete remission, 1 case （160 mg/kg） partial remission, but 4 cases didn＇t achieve remission. One case reached remission after Rituximab （RTX） was introduced. One case got partial remission after Leflunomide （LEF） was introduced, and the complete remission rate was higher in those treated with combined therapy of glucocorticoid and CsA than those treated with glucocorticoid only（ 76.5% vs 12.5 % ,P = 0.004 ） , but the total efficacy showed no difference （94.2% vs 62.5%, P = 0. 081 ）. The complete remission rate （76.5% vs 38.5%, P = 0. 042） and total efficacy （94. 1% vs 61.5 %, P = 0. 040） were higher in those with combined therapy of steroid and CsA than those treated withsteroid and other immunosuppressor. The complete remission rate （76.5% vs 16.7%, P=0. 018 ） and total efficacy （94. 1% vs 33.3 %, P = 0.008） were also higher than those treated with steroid and CTX, but the complete remission rate（76.5% vs 80.0%, P = 0. 687 ） and total efficacy （94.1% vs 100.0%, P = 0. 773 ） showed no difference com- pared with those treated with steroid and MMF. Conelusions IMN shows glucocorticoid resistance mostly, while CsA had definite efficiency and may be better than CTX. And the efficiency of MMF should be noted.