他克莫司在儿童原发性肾病综合征中的应用

Clinical application of tacrolimus in children with primary nephrotic syndrome

目的研究他克莫司（TAC，FK506）在儿童原发性肾病综合征中的临床应用。方法65例患儿入院后根据不同的临床类型联合激素或逐渐减用激素，同时给予口服他克莫司，剂量0．1～0．15mg／kg，每12小时1次，疗程6～24个月，并监测血药浓度。结果65例患儿经他克莫司治疗1-2个月后，尿蛋白逐渐减少；血清白蛋白迅速增加并恢复正常；胆固醇、三酰甘油均有不同程度的改善；总缓解率83．1％；显效时间为7—54d。随访中12例出现复发。细胞亚群CD4增高时缓解率高。他克莫司药物代谢基因型为3／3型或3／1型缓解率高。微小病变型肾病（MCN）缓解率为96．4％；系膜增生性。肾炎（MsPGN）为90．0％；膜性肾病（MN）为2／3；膜增生性肾炎（MPGN）为3／5；局灶节段性肾小球硬化症（FSGS）为4／9。他克莫司起始剂量为0．1—0．15mg／kg，每12小时1次，治疗浓度控制在5—10g／L时，本组患儿可获得缓解。12例出现厌食、恶心、呕吐；1例腹痛；2例头痛；1例震颤；3例失眠；4例出现一过性Scr上升；8例N-乙酰氨基葡萄糖苷酶（NAG）轻微增加；6例C3与α-2巨球蛋白增加。部分患儿在1周内恢复正常，其他患儿在他克莫司减药后症状消失。结论他克莫司对原发性肾病综合征患儿有良好的疗效，即使患儿肝功能异常、并发结核感染或有严重激素不良反应。他克莫司可替代环孢素A作为新的治疗用药。

Objective To investigate the clinical application of tacrolimus （TAC, FK506） in children with primary nephrotic syndrome （NS）. Methods Sixty-five primary NS children received routine or decreased-dosage glueocorticosteroid according to clinical NS types after hospitalization. At the same time, TAC was given orally with the dosage of 0.1 to 0.15 mg/kg, once every 12 hours, for 6 to 24 months. And the serum concentration of TAC was monitored during the course. Results After the treatment of TAC for 1 to 2 months, 65 patients were recovered with gradually reduced urinary protein, rapidly increased serum albumin, and improvement of cholesterol and triglycerides. Total remission rate was 83.1% and onset time was 7 to 54 days. Twelve cases experienced recurrence. Increased CD4, as well as 3/3 or 3/1 TAC genotype, indicated higher remission rate. Various pathological types had different remission rates or ratio, which were as follows： minimal change nephropathy （96.4%）, mesangial proliferative glomerulonephritis （90.0% ）, membranous nephropathy （2/3）, membranous proliferative glomerulonephritis （3/5）, focal segmental glomerulosclerosis （4/9）. The patients would recover in the course of treatment under the conditions of TAC initial dose as 0.1 to 0.15 mg /kg per 12 hours and controlled serum concentration as 5 to 10 g/L. During the treatment, 12 cases appeared gastrointestinal symptoms, mainly as anorexia, nausea and vomiting, 1 abdominal pain, 2 headache, 1 tremor, 1 paresthesia, 3 insomnia, 4 transient increased Scr, 8 slightly increased NAG, 6 increased C3 and α-2 macroglobulin. The symptoms disappeared within one week or after stopping TAC. Conclusions TAC is effective in primary NS children, even with abnormal liver function or tuberculosis infection. TAC can also be a substitute to eyelosporine A.