突触素
他克莫司
医学
钙调神经磷酸酶
蛋白尿
泌尿科
膜性肾病
局灶节段性肾小球硬化
肾病综合征
内科学
胃肠病学
肾病
肾活检
内分泌学
肾功能
移植
足细胞
肾
糖尿病
作者
Qingxian Zhang,Sufang Shi,Li Zhu,Jicheng Lv,Lijun Liu,Yuqing Chen,Hong Zhang,Haiyan Wang
出处
期刊:American Journal of Nephrology
[S. Karger AG]
日期:2012-01-01
卷期号:35 (4): 312-320
被引量:43
摘要
<i>Background:</i> Tacrolimus has been reported to be effective in refractory nephrotic syndrome, such as focal segmental glomerulosclerosis and membranous nephropathy. Some IgA nephropathy (IgAN) patients with massive proteinuria showed resistance to steroids and/or cytotoxic immunosuppressants based on the supportive therapy with renin- angiotensin system blockade. The efficacy and safety of tacrolimus in such refractory IgAN patients are extremely ambiguous, and the mechanism of tacrolimus improving proteinuria remission needs to be investigated. <i>Methods:</i> 14 refractory IgAN patients were enrolled. The patients received tacrolimus (0.05–0.1 mg/kg/day) and prednisone (0.5 mg/kg/day) for at least 6 months. Synaptopodin and calcineurin expression were detected in renal tissues of patients who received re-biopsy. A puromycin aminonucleoside (PAN)-induced human podocyte injury model was applied to investigate the possible role of tacrolimus in proteinuria remission. <i>Results:</i> Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline. In 11 patients treated with tacrolimus over 6 months, 9 showed complete or partial remission and 7 achieved remission within 1 month. In renal tissues, the expression of calcineurin increased while synaptopodin decreased and recovered partially after tacrolimus therapy. In an in vitro study, F-actin disrupted in human podocytes after stimulation of PAN, while calcineurin increased and synaptopodin decreased. After co-treatment with tacrolimus the reorganization of F-actin and the expression of calcineurin and synaptopodin recovered. <i>Conclusions:</i> Tacrolimus showed a rapid proteinuria remission in refractory IgAN patients. The possible mechanism of tacrolimus to proteinuria remission might be podocyte cytoskeleton stabilization through inhibition of calcineurin expression.
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