Li Xiayu, Li Heng, Ye Huijuan, Li Qun, He Xuelin, Zhang Xiaohui, Chen Yilun, Han Fei, He Qiang, Wang Huipin, Chen Jianghua
Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
Am J Kidney Dis. 2009 Jul;54(1):51-8. doi: 10.1053/j.ajkd.2009.02.018. Epub 2009 May 5.
BACKGROUND: In a proportion of adults with steroid-resistant nephrotic syndrome (SRNS), intravenous cyclophosphamide therapy fails. Tacrolimus may be a promising alternative to cyclophosphamide for such patients. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 19 adults with SRNS (6 with minimal change nephropathy, 8 with focal segmental glomerulosclerosis [FSGS], and 5 with mesangioproliferative glomerulonephritis) that did not respond to intravenous cyclophosphamide therapy were studied from January 2003 to September 2006. Oral tacrolimus was administered (target trough levels, 5 to 10 ng/mL) for 24 weeks, then reduced doses were given (target trough level, 3 to 6 ng/mL) for another 24 weeks. FACTORS: Histopathologic types: minimal change nephropathy (n = 6), FSGS (n = 8), and mesangioproliferative glomerulonephritis (n = 5). MEASUREMENTS: outcome variables included complete remission (decrease in daily proteinuria to protein < or = 0.3 g/d), partial remission (decrease in daily proteinuria to protein < 3.5 g/d but > 0.3 g/d), relapse (increase in daily proteinuria to protein > or = 3.5 g/d in patients who had partial or complete remission), change in kidney function, and tacrolimus dosing and serum levels. RESULTS: 17 patients completed at least 24 weeks of tacrolimus therapy. Complete remission was achieved in 11 patients (64.7%), and partial remission was achieved in 3 (17.6%). Complete or partial remission was achieved in 5 of 5 patients with minimal change nephropathy, 4 of 7 patients with FSGS, and 5 of 5 patients with mesangioproliferative glomerulonephritis. Primary resistance to tacrolimus was seen in 3 patients (17.6%), all with FSGS. Mean times to achieve partial and complete remission were 5.6 +/- 1.4 and 8.0 +/- 5.1 weeks, respectively. In patients who achieved complete or partial remission, 35.7% experienced relapse during follow-up (mean, 37.6 +/- 13.4 months). Two patients had doubling of serum creatinine levels, both with FSGS. LIMITATIONS: Observational study. CONCLUSIONS: Tacrolimus rapidly and effectively induced remission of SRNS in Chinese adults with disease refractory to treatment with intravenous cyclophosphamide. Treatment may be less effective in patients with FSGS.
背景：在一部分患有类固醇抵抗性肾病综合征（SRNS）的成年人中，静脉注射环磷酰胺治疗无效。对于这类患者，他克莫司可能是一种有前景的环磷酰胺替代药物。 研究设计：前瞻性观察研究。 研究地点与参与者：2003年1月至2006年9月，对19例对静脉注射环磷酰胺治疗无反应的SRNS成年人（6例为微小病变肾病，8例为局灶节段性肾小球硬化[FSGS]，5例为系膜增生性肾小球肾炎）进行了研究。口服他克莫司（目标谷浓度为5至10 ng/mL）24周，然后减量（目标谷浓度为3至6 ng/mL）再治疗24周。 因素：组织病理学类型：微小病变肾病（n = 6）、FSGS（n = 8）和系膜增生性肾小球肾炎（n = 5）。 测量指标：结局变量包括完全缓解（每日蛋白尿减少至蛋白≤0.3 g/d）、部分缓解（每日蛋白尿减少至蛋白<3.5 g/d但>0.3 g/d）、复发（部分或完全缓解的患者每日蛋白尿增加至蛋白≥3.5 g/d）、肾功能变化以及他克莫司剂量和血清水平。 结果：17例患者完成了至少24周的他克莫司治疗。11例患者（64.7%）实现了完全缓解，3例（17.6%）实现了部分缓解。5例微小病变肾病患者中有5例实现了完全或部分缓解，7例FSGS患者中有4例，5例系膜增生性肾小球肾炎患者中有5例。3例患者（17.6%）对他克莫司原发性耐药，均为FSGS。实现部分和完全缓解的平均时间分别为5.6±1.4周和8.0±5.1周。在实现完全或部分缓解的患者中，35.7%在随访期间复发（平均37.6±13.4个月）。2例患者血清肌酐水平翻倍，均为FSGS。 局限性：观察性研究。 结论：他克莫司能迅速有效地诱导对静脉注射环磷酰胺治疗难治的中国成年SRNS患者缓解。对于FSGS患者，治疗效果可能较差。
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