摘要目的 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0.1～0.15 mg/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7～54 d.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0.1～0.15 mg/kg,每12小时1次,治疗浓度控制在5～10 g/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.

abstractsObjective To investigate the clinical application of tacrulimus (TAC, FK506) in children with primary nephrotic syndrome (NS). Methods Sixty-five primary NS children received routine or decreased-dosage glucocorticosteroid 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 glomendonephritis (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 cyclosporine A.