Tacrolimus Improves the Proteinuria Remission in Patients with Refractory IgA Nephropathy

被引:80
作者
Zhang, Qingxian [1 ]
Shi, Su-fang [1 ]
Zhu, Li [1 ]
Lv, Ji-cheng [1 ]
Liu, Li-jun [1 ]
Chen, Yu-qing [1 ]
Zhang, Hong [1 ]
Wang, Hai-yan [1 ]
机构
[1] Peking Univ, Dept Med,Minist Educ,Div Renal,Hosp 1, Inst Nephrol,Key Lab Renal Dis,Minist Hlth China, Key Lab Chron Kidney Dis Prevent & Treatment, Beijing 100034, Peoples R China
关键词
IgA nephropathy; Tacrolimus; Proteinuria; Podocyte; Cytoskeleton; NEPHROTIC SYNDROME; CONTROLLED-TRIAL; PODOCYTES; GLOMERULOSCLEROSIS; THERAPY; INJURY; INHIBITOR; PROGNOSIS; DISEASE;
D O I
10.1159/000337175
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background: 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. Methods: 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. Results: Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline.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. Conclusions: 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. Copyright (C) 2012 S. Karger AG, Basel
引用
收藏
页码:312 / 320
页数:9
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