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有读书笔记Tacrolimus therapy in adults with steroid- and cyclophosphamide-resistant nephrotic syndrome and normal or mildly reduced GFR

热5 qxm123 添加于 2010-5-2 15:30 | 1852 次阅读 | 1 个评论

  •  作 者

    Li X, Li H, Ye H, Li Q, He X, Zhang X, Chen Y, Han F, He Q, Wang H, Chen J

  •  摘 要

    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). OUTCOMES: 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.

  •  详细资料

    • 关键词: Administration, Oral; Adolescent; Adult; China; Creatinine/blood; Cyclophosphamide/administration & dosage/*therapeutic use; *Drug Resistance; Female; Follow-Up Studies; Glomerular Filtration Rate/drug effects/*physiology; Glomerulonephritis, Membranoproliferative/blood/drug therapy/physiopathology; Glomerulosclerosis, Focal Segmental/blood/drug therapy/physiopathology; Humans; Immunosuppressive Agents/administration & dosage/pharmacology/*therapeutic use; Injections, Intravenous; Male;
    • 文献种类:期刊
    • 期刊名称: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    • 期刊缩写: Am J Kidney Dis
    • 期卷页: 2009年  第54卷 第1期 51-58页
    • 地址: Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China
    • ISBN: 0272-6386
    • 备注:PMID:19406543

  • 相关链接 DOI URL 

  •  qxm123 的文献笔记  订阅

    部分激素耐药的肾病综合征（SRNS）成人患者接受静脉环磷酰胺治疗无效，中国浙江大学李（Li X）等的一项前瞻性研究证实，对于这类病人他克莫司有望取代环磷酰胺。

    　　研究选取2003年1月至2006年9月期间19例接受静脉环磷酰胺治疗无效的成人SRNS患者［6例微小病变性肾病、8例局灶节段性肾小球硬化（FSGS）、5例系膜增生性肾小球肾炎］作为研究对象，给患者口服他克莫司（目标谷浓度5～10 ng/ml）治疗24周，然后再减量（目标谷浓度3～6 ng/ml）治疗24周。

    　　结果发现，在完成了至少24周治疗的17例患者中，有11例达到完全缓解（CR）、3例达到部分缓解（PR）。5例微小病变性肾病患者均达到CR或PR，7例FSGS患者中有4例达CR或PR，5例系膜增殖性肾小球肾炎患者均达CR或PR，3例出现他克莫司原发耐药者均是FSGS患者。从治疗开始至PR和CR的平均时间分别是(5.6±1.4)周和(8.0±5.1)周。在达到CR或PR的患者中，35.7％在随访期间［平均(37.6±13.4)月］病情复发，有2例FSGS患者的血清肌酐水平加倍。

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