Letavernier Emmanuel, Legendre Christophe
Transplantation Unit, Hôpital Necker, 75743 Paris, France.
Transplant Rev (Orlando). 2008 Apr;22(2):125-30. doi: 10.1016/j.trre.2007.12.001.
Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Because proteinuria is a major predictive factor of poor transplantation outcome, many studies focused on this adverse event during the past years. Whether proteinuria was due to sirolimus or only a consequence of calcineurin inhibitors withdrawal remained unsolved until high range proteinuria has been observed during sirolimus therapy in islet transplantation and in patients who received sirolimus de novo. Podocyte injury and focal segmental glomerulosclerosis have been related to mToR inhibition in some patients, but the pathways underlying these lesions remain hypothetic. We discuss herein the possible mechanisms and the significance of mToR blockade-induced proteinuria.
在患有慢性移植肾肾病的肾移植受者中，从钙调神经磷酸酶抑制剂转换为雷帕霉素哺乳动物靶蛋白（mToR）抑制剂，尤其是西罗莫司后，观察到大量尿蛋白排泄。由于蛋白尿是移植预后不良的主要预测因素，在过去几年中，许多研究都聚焦于这一不良事件。在胰岛移植以及初治接受西罗莫司治疗的患者中观察到大量蛋白尿之前，蛋白尿是由西罗莫司引起还是仅仅是停用钙调神经磷酸酶抑制剂的结果一直没有得到解决。在一些患者中，足细胞损伤和局灶节段性肾小球硬化与mToR抑制有关，但这些病变的潜在机制仍属推测。我们在此讨论mToR阻断诱导蛋白尿的可能机制及意义。
