他克莫司治疗儿童难治性肾病综合征191例

Clinical analysis of Tacrolimus treatment on 191 patients with pediatric refractory nephrotic syndrome

目的 探讨他克莫司（TAC）治疗儿童难治性肾病综合征的临床疗效。方法 选择2010年1月至2013年12月在南京军区南京总医院儿科住院的难治性肾病综合征患儿191例，其中激素依赖型101例、激素耐药型73例、频繁复发型17例。每例患儿均使用TAC，在用药过程中监测 TAC血药浓度，并根据不同情况减量使用糖皮质激素及停用相关其他免疫抑制剂。分别于治疗前和治疗4周、8周观察相关临床和实验室检测指标的变化。结果 191例患儿经TAC治疗8周后总缓解率达86.9%（166/191例），最早显效时间6 d，治疗后血浆清蛋白、血脂等临床生化指标明显改善，差异均有统计学意义（P 均 〈0.01），蛋白尿明显减轻（t=20.14，P 〈0.01）。191例中有 115例行肾活检，其中微小病变型（MCN）疗效最好，缓解率达 90.5%（19/21例），其次为系膜增生性肾小球肾炎（MsPGS），缓解率达87.7%（57/65例），局灶节段性硬化（FSGS）、膜性肾病（MN）、膜增生性肾小球肾炎（MPGN）也有不同程度缓解。本组病例有32例测定 TAC 药物代谢基因型P450Cyp3A5，3/3型和1/3型合并在一起总缓解率为75.0%（21/28例），而4例1/1型治疗4周无一例缓解。本组病例治疗过程中不良反应较少，多为轻微消化道症状、一过性肾功能损害、血糖异常、头痛、烦躁及肢体疼痛等，不影响治疗进程。结论 针对儿童难治性肾病综合征的治疗，TAC是一种不良反应少、有临床疗效的强效免疫抑制剂，有着良好的应用前景。

Objective To explore the clinical effect of Tacrolimus in pediatric refractory nephrotic syndrome. Methods One hundred and ninety -one children with refractory nephrotic syndrome in Nanjing General Hospital of Nanjing Military Region,People＇s Liberation Army,were enrolled from January 2010 to December 2013, including 101 cases of steroid- dependent nephrotic syndrome,73 cases of steroid- dependent nephrotic syndrome,and 17 cases of frequently relapsing nephrotie syndrome. Tacrolimus was applied to all the patients. The plasma concentrations of Ta- crolimus during the treatment were measured and glucocorticoid tapered or some other ts discontinued based on clinical judgment. Relevant clinical changes and laboratory test values were observed before treatment and in weeks 4,8 after treatment. Results The overall remission rate was 86.9% （ 166/191 cases） after 8 weeks treatment of Tacrolimus. The minimum effective time was 6 days. Serum albumin and cholesterol significantly improved（ all P 〈 0.01 ）, and proteinuria also diminished markedly（ t =20. 14 ,P 〈 0.01 ）. One hundred and fifteen patients underwent renal biopsy. The treatment with Tacrolimus did well in minimal change nephropathy（MCN） [ remission rate was 90.5% （18/21 cases） ], but mesangial proliferative glomerulonephritis （MsPGS） was inferior in its efficacy （ 87.7% ） （ 57/65 cases ）. The use of Tacrolimus in focal segmental glomerulosclerosis（FSGS） ,membranous nephropathy（MN） and membranoproliferative glomerulonephritis（MPGN） also produced remission to some extent. Thirty - two cases were analyzed by way of Ta- crolimus metabolic genotype. The remission rate of 3/3 or 1/3 Tacrolimus metabolic genotype was 75.0% （21/28 cases）, but 4 cases with 1/1 tacrolimus metabolic genotype did not remit after 4 weeks treatment. The adverse reactions of tacroli- mus were mild,mainly slight digest tract symptoms,transient kidney injury, dysglycemia,headache, dysphoria etc,which did not influence the treatment. Conclusions Tacrolimus has a gold application prospect, and is a powerfully effective immunosuppressant with clinical efficacy and less side effects for refractory nephritic syndrome in children.