霉酚酸酯和环孢素A治疗儿童原发性难治性肾病综合征的临床疗效观察

Mycophenolate mofetil versus cyclosporine A in children with primary refractory nephroticsyndrome

目的比较霉酚酸酯和环孢素A治疗儿童原发性难治性肾病综合征的疗效和安全性。方法采用前瞻性的随机对照临床研究,将2013年10月至2015年10月在首都儿科研究所附属儿童医院肾脏内科住院并诊断儿童原发性肾病综合征的62例患儿（其中男44例，女18例，年龄2.1~17.0岁，包括频复发32例，激素耐药30例），用数字表法随机分为霉酚酸酯组或环孢素A组，分别予以霉酚酸酯20~30mg/（kg·d）或环孢素A 3~5 mg/（kg·d）起始剂量联合泼尼松治疗,定期随访1年。采用秩和检验或Fisher检验，比较两组的治疗有效率、复发频率、诱导缓解时间、维持缓解时间，以及糖皮质激素用量等指标。结果（1）62例中17例行肾活检，微小病变8例，系膜增生性肾小球肾炎5例，膜性肾病2例，局灶节段性肾小球硬化2例。（2）对频复发患儿疗效比较：频复发患儿霉酚酸酯组14例，环孢素A组18例。治疗后环孢素A组的复发频率（次/年）低于霉酚酸酯组[1.0（0.0，1.0）比1.0（1.0，3.0），Z=-2.405，P=0.016]，维持缓解时间（月）长于霉酚酸酯组[10.0（5.7，12.1）比5.0（1.0，11.0），Z=-1.984，P=0.047]。随访1年时，环孢素A组与霉酚酸酯组糖皮质激素用量差异无统计学意义。（3）对激素耐药患儿疗效比较：总有效率：霉酚酸酯组6/14，环孢素A组13/16；完全缓解率：霉酚酸酯组4/14，环孢素A12/16（P〈0.05）。环孢素A组诱导缓解所需时间（月）短于霉酚酸酯组[1.0（1.0，2.0）比3.0（2.5，4.0），Z=-2.529，P=0.011]。两组在维持缓解时间、降低复发频率上差异无统计学意义。（4）除环孢素A组1例患儿发生高血压脑病外，未观测到其他严重不良反应，两组患儿不良反应发生率比较差异无统计学意义。结论霉酚酸酯和环孢素A治疗儿童原发性难治性肾病综合征均有较好疗效；在降低频复发患儿的复发频率以及促进激素耐药患儿完全缓解方面，环孢素A的疗效优于霉酚酸酯。多数患儿可耐受霉酚酸酯或环孢素A的治疗，但应密切监测环孢素A的药物毒性。

ObjectiveTo compare the efficacy and safety of mycophenolate mofetil versus cyclosporine A in treating children with primary refractory nephrotic syndrome.MethodsConducted a prospective randomized controlled clinical trial in 62 pediatric patients （including 44 boys and 18 girls）, age ranged from 2.1 to 17.0 years; 32 cases presented with frequently relapsing nephrotic syndrome （FRNS） and 30 cases presented with steroid-resistant nephrotic syndrome （SRNS）, who were admitted to department of Nephrology, Children＇s Hospital Affiliated to Capital Institute of Pediatrics from October 2013 to October 2015. The patients received either mycophenolate mofetil （20-30）mg/（kg·d） or cyclosporine A （3-5）mg/（kg·d） randomly, on the basis of prednisone treatment. Follow-up interview was conducted regularly for at least one year. Efficacy rate, relapse rate, time required for induction of remission, relapse-free period and prednisone dosage were compared between the two groups.Results（1） Renal histologic examination, which was available for 17 patients, revealed minimal change disease in 8 patients, mesangial proliferative glomerulonephritis （MsPGN） in five, membranous nephropathy in two, and focal segmental glomerulosclerosis （FSGS） in two. （2） Comparison of mycophenolate mofetil versus cyclosporine A in children with FRNS： There were 14 patients with FRNS in mycophenolate mofetil group and 18 patients with FRNS in cyclosporine A group respectively. The relapse rate （episodes/year） in cyclosporine A group was lower than that of mycophenolate mofetil group （1.0 （0.0, 1.0） vs. 1.0 （1.0, 3.0）, Z=-2.405, P=0.016）. The relapse-free period （months） in cyclosporine A group was longer than that of mycophenolate mofetil group （10.0 （5.7, 12.1） vs. 5.0 （1.0, 11.0）, Z=-1.984, P=0.047）. No significant difference in dosage of prednisone was found between cyclosporine A and mycophenolate mofetil groups when followed up for 1 year. （3） Comparison of mycophenolate mofetil versus cyclosporine A in children with SRNS： The efficacy rate was 6/14 in mycophenolate mofetil group and 13/16 in cyclosporine A group. The complete remission rate was 4/14 in mycophenolate mofetil group and 12/16 in cyclosporine A group （P〈0.05）. The time （months） required for induction of remission in cyclosporine A group was significantly shorter than that of mycophenolate mofetil group （1.0 （1.0, 2.0） vs. 3.0 （2.5, 4.0）, Z=-2.529, P=0.011）. No significant differences were found between the two groups with respect to relapse-free period and relapse rate. （4） Except that one patient developed hypertensive encephalopathy in cyclosporine A group, no other serious adverse events were recorded. There were no significant differences between two groups with respect to adverse events.ConclusionOur results indicated that both mycophenolate mofetil and cyclosporine A were effective in the treatment of children with refractory nephrotic syndrome. Cyclosporine A was superior to mycophenolate mofetil in preventing relapses in patients with FRNS and inducing complete remission in patients with SRNS. Although most patients were able to tolerate mycophenolate mofetil and cyclosporine A, but the toxicity and safety of cyclosporine A should be monitored closely.