促肾上腺皮质激素应用于原发性肾病综合征频复发及激素依赖患儿疗效及安全性初探

Preliminary study on the efficacy and safety of adrenocorticotropic hormone on the treatment of children with steroid-dependent and frequently relapsed primary nephrotic syndrome

目的探讨促肾上腺皮质激素(ACTH)治疗原发性肾病综合征(PNS)频复发或激素依赖患儿的疗效和安全性。方法以符合PNS频复发或激素依赖患儿为ACTH组,每月给予ACTH缓慢静滴3～5d,并逐渐激素减量至停药;以激素维持治疗PNS患儿为对照组。观察治疗前与治疗后3、6和12个月两组激素剂量、复发次数、肾上腺皮质功能及不良反应。结果 2010年9～12月ACTH组纳入14例,对照组纳入6例。①ACTH组12/14例均能顺利将激素减量至停药,无复发;2例因感染尿蛋白波动,感染控制后尿蛋白仍阳性,激素加量至尿蛋白转阴后减量,继续ACTH冲击,其中1例因感染后再次复发,停用ACTH改用他克莫司。ACTH组13例进入分析。②ACTH组治疗后3、6和12个月激素剂量与治疗前差异有统计学意义(P<0.05);对照组治疗后3、6和12个月激素剂量与治疗前差异无统计学意义(P>0.05);ACTH组与对照组治疗后6、12个月激素剂量差异有统计学意义(P<0.05)。③治疗前ACTH组和对照组均存在肾上腺皮质功能低下,ACTH组13例在治疗3、6和12个月分别有9、11和13例肾上腺皮质功能恢复正常;对照组6例12个月治疗期间均表现为肾上腺皮质功能低下。④ACTH组观察到腰部皮疹和心率加快各1例。⑤ACTH组治疗后6、12个月身高与治疗前差异有统计学意义,对照组治疗前后身高差异无统计学意义(P>0.05)。ACTH组治疗前后体重差异无统计学意义,对照组治疗后6、12个月体重与治疗前差异有统计学意义(P<0.05)。⑥ACTH组和对照组治疗前后骨密度差异均无统计学意义(P>0.05)。结论 ACTH治疗PNS频复发或激素依赖患儿有一定疗效,可避免长期激素治疗的不良反应,值得进一步探讨。

Objective To investigate the efficacy and clinical significance of adrenocorticotropic hormone on the treatment of children with steroid-dependent and frequently relapsed primary nephrotic syndrome （PNS）. Methods Children enrolled in this study all met the diagnostic criteria of PNS characterized by steroid-dependent and frequent relapse. ACTH was intravenously drip ped slowly for 3 -5 days every month , and each case was gradually reduced glucocorticosteroid until withdrawal. Simultaneously, the adrenocortical function was evaluated. Six children with maintenaned glucocorticosteroid treatment were as controls. Results From September to December 2010, 14 children were recruited into ACTH group and 6 into control group. （1）12 cases of the ACTH group could be successfully reduced the dosage of hormone to withdrawal without recurrence. Urinary protein of 2 cases fluctuated due to infection and remained positive when the infection was under the control, and the dosage of GC increased. When urine protein changed to be negative, the dosage of GC reduced and ACTH impact was continued to be used. One case relapsed due to infection, the ACTH treatment was stopped and tacrolimus was used. （2） There was significant difference between 3, 6, 12 months usage of GC and before treatment in ACTH group （P 〈 0.05 ）. There was no difference between 3, 6, 12 months usage of GC andbefore treatment in control group （ P 〉 0.05 ）. There was significant difference between ACTH group and control group after 6 and 12 months usage of GC （P 〈 0.05 ）. （3） Before treatment, the function of adrenal cortex in both ACTH and control groups was insufficiency. The function of adrenal cortex of 13 cases in ACTH group became normal in 9, 11, and 13 cases after the treatment of 3, 6 and 12 months, respectively. The function of adrenal cortex of 6 cases in the control group all decreased. （4） In ACTH group, 1 case had waist rash and 1 case heart rate speeded up. （5） There was significant difference in height between the treatment of 6, 12 months and before treatment in ACTH group. There was no difference in height before and after treatment in control group （ P 〈 0. 05）. There was no significant difference in weight between the treatment of 3,6, 12 months and before treatment in ACTH group. There was significant difference in weight between the treatment of 6, 12 months and before treatment in control group （P 〈 0.05 ）. （6） There was significant difference in bone mineral density before and after treatment in ACTH and control groups （ P 〉 0.05） . Conclusions ACTH is effective to children with steroid-dependent nephrotic syndrome. Less side effects are observed compared with long-term application of glucocorticosteroid. Further studies are needed to confirm the findings.