Loss of Nephrin Expression in Glomeruli of Kidney-Transplanted Patients Under m-TOR Inhibitor Therapy
Loss of Nephrin Expression in Glomeruli of Kidney-Transplanted Patients Under m-TOR Inhibitor Therapy
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DOI：
10.1111/j.1600-6143.2010.03259.x
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发表时间：
2010-10-01
影响因子：
8.8
通讯作者：
Segoloni, G. P.
中科院分区：
文献类型：
--
作者：
Biancone, L.;Bussolati, B.;Segoloni, G. P.
在接受m-TOR抑制剂（m-TORi）治疗的肾移植患者中观察到蛋白尿的发生。最近的研究表明，m-TORi（s）可能会改变肾小球足细胞的行为和完整性。我们分析了肾移植患者的肾活检组织，并评估了nephrin的表达，nephrin是肾小球裂膜的关键成分。在一组接受“从头”m-TORi治疗的患者中，与移植前供体活检相比，所有病例中肾小球内nephrin的表达均显著降低。来自未用m-TORi治疗的对照移植患者的活组织检查未能表现出nephrin的丢失。在随后转换为m-TORi治疗的一组患者中，在引入m-TORi之前进行的方案活检也可用。nephrin在m-TORi前活检组织中的表达与在移植前供体活检组织中观察到的相似，但在引入m-TORi后显著降低。在该组中，m-TORi启动后蛋白尿增加。然而，在某些情况下，尽管nephrin减少，但蛋白尿仍然正常。在体外，西罗莫司下调人足细胞nephrin的表达。我们的研究结果表明，m-TORi（s）可能会影响肾移植患者nephrin的表达，与体外培养足细胞的观察结果一致。
The development of proteinuria has been observed in kidney-transplanted patients on m-TOR inhibitor (m-TORi) treatment. Recent studies suggest that m-TORi(s) may alter the behavior and integrity of glomerular podocytes. We analyzed renal biopsies from kidney-transplanted patients and evaluated the expression of nephrin, a critical component of the glomerular slit-diaphragm. In a group of patients on 'de novo' m-TORi-treatment, the expression of nephrin within glomeruli was significantly reduced in all cases compared to pretransplant donor biopsies. Biopsies from control transplant patients not treated with m-TORi(s) failed to present a loss of nephrin. In a group of patients subsequently converted to m-TORi-treatment, a protocol biopsy performed before introduction of m-TORi was also available. The expression of nephrin in the pre-m-TORi biopsies was similar to that observed in the pretransplant donor biopsies but was significantly reduced after introduction of m-TORi(s). Proteinuria increased after the m-TORi inititiation in this group. However, in some cases proteinuria remained normal despite reduction of nephrin. In vitro, sirolimus downregulated nephrin expression by human podocytes. Our results suggest that m-TORi(s) may affect nephrin expression in kidney-transplanted patients, consistently with the observation in vitro on cultured podocytes.