Kamar N, Rostaing L
Service de Néphrologie, Dialyse et Transplantation d'organes, CHU de Toulouse-Rangueil, 1, avenue Jean-Poulhès, TSA 50032, 31059 Toulouse cedex 09, France.
Nephrol Ther. 2008 Jun;4 Suppl 1:S13-S17. doi: 10.1016/S1769-7255(08)73646-0.
Chronic allograft nephropathy is characterized by an increase over time of interstitial fibrosis, tubular atrophy, fibrointimal thickening, arteriolar hyalinosis and glomerulosclerosis, resulting in progressive renal dysfunction. It is mainly caused by calcineurin inhibitors-induced nephrotoxicity, which is related to an imbalance between vasoconstrictor and vasodilator factors. Cyclosporine A-induced nephrotoxicity is particularly due to the activation of pro-apoptotic genes leading to tubular atrophy with tubular cell apoptosis and to hemodynamic changes inducing interstitial fibrosis by the activation of factors stimulating the fibroblast proliferation (TGFbeta, Endothelin-A and Plasminogen activator inhibitor-1). Calcineurin inhibitors (CNI) treatment monitoring is essentially based on histology, but a better follow-up of drug exposure post-transplantation leading to a regular and rapid adjustment of the doses to avoid extended periods of overexposure, could enable to decrease their nephrotoxicity and improve graft survival in treated patients. CNIs dose reduction or conversion to proliferating signal inhibitors may be a therapeutic alternative.
慢性移植肾肾病的特征是随着时间推移，间质纤维化、肾小管萎缩、纤维内膜增厚、小动脉玻璃样变和肾小球硬化逐渐加重，导致肾功能进行性减退。其主要由钙调神经磷酸酶抑制剂诱导的肾毒性引起，这与血管收缩因子和血管舒张因子之间的失衡有关。环孢素A诱导的肾毒性尤其归因于促凋亡基因的激活，导致肾小管萎缩伴肾小管细胞凋亡，以及血流动力学变化，通过刺激成纤维细胞增殖的因子（转化生长因子β、内皮素-A和纤溶酶原激活物抑制剂-1）的激活诱导间质纤维化。钙调神经磷酸酶抑制剂（CNI）治疗监测主要基于组织学检查，但更好地跟踪移植后药物暴露情况，从而定期快速调整剂量以避免长时间过度暴露，可能会降低其肾毒性并提高接受治疗患者的移植物存活率。减少CNI剂量或转换为增殖信号抑制剂可能是一种治疗选择。
