Hamar Péter, Lipták Péter, Heemann Uwe, Iványi Béla
Institute of Pathophysiology, Faculty of General Medicine, Semmelweis University, Budapest, Hungary.
Transpl Int. 2005 Jul;18(7):863-70. doi: 10.1111/j.1432-2277.2005.00146.x.
Chronic allograft nephropathy (CAN) is the leading cause of graft loss following kidney transplantation. One factor contributing to CAN is chronic alloimmune injury. However, the involvement of alloantigen-dependent and -independent factors in CAN is unclear. The pathomechanism of CAN has been extensively studied by utilizing the Fischer-to-Lewis (F344-to-LEW) rat model. Transplant capillaropathy (circumferential multiplication of the peritubular capillary basement membrane) and transplant glomerulopathy (reduplication of the glomerular basement membrane) have recently been validated clinicopathologically as ultrastructural indicators of chronic alloimmune injury. To investigate the presence of these markers, F344-to-LEW kidneys were examined by electron and light microscopy 32, 40 and 52 weeks after implantation. F344 rats with or without 30-min ischemia of the left kidney following right nephrectomy served as controls. All transplanted rats displayed marked proteinuria. On electron microscopy, transplant capillaropathy, transplant glomerulopathy, and T-cell cytotoxicity (indicator of ongoing cellular rejection) were absent. On light microscopy, the arteries were devoid of intimal fibrosis. Focal-segmental glomerulopathy resembling hyperfiltration injury was encountered, with mild interstitial infiltration, fibrosis, and tubular atrophy. The proteinuria and kidney pathology were more severe in transplanted than in ischemic or uninephrectomized rats. Because chronic-active rejection could not be detected between weeks 32 and 52, we propose that the alloantigen-dependent initial graft injury subsides, but induces the late events: glomerular hyperfiltration, proteinuria, and glomerulosclerosis. Accordingly, the model - in the late phase - is suitable to investigate alloantigen-independent factors of CAN and lacks markers of alloantigen-dependent processes.
慢性移植肾肾病（CAN）是肾移植后移植肾丢失的主要原因。导致CAN的一个因素是慢性同种免疫损伤。然而，同种抗原依赖性和非依赖性因素在CAN中的作用尚不清楚。利用Fischer-to-Lewis（F344-to-LEW）大鼠模型对CAN的发病机制进行了广泛研究。移植性毛细血管病（肾小管周围毛细血管基底膜的周向增殖）和移植性肾小球病（肾小球基底膜的重复）最近在临床病理上被确认为慢性同种免疫损伤的超微结构指标。为了研究这些标志物的存在情况，在植入后32、40和52周对F344-to-LEW肾进行电子显微镜和光学显微镜检查。右肾切除术后左肾有或无30分钟缺血的F344大鼠作为对照。所有移植大鼠均出现明显蛋白尿。电子显微镜检查显示，无移植性毛细血管病、移植性肾小球病和T细胞细胞毒性（正在进行的细胞排斥反应指标）。光学显微镜检查显示，动脉无内膜纤维化。出现了类似于超滤损伤的局灶节段性肾小球病，伴有轻度间质浸润、纤维化和肾小管萎缩。移植大鼠的蛋白尿和肾脏病理改变比缺血或单侧肾切除大鼠更严重。由于在32至52周之间未检测到慢性活动性排斥反应，我们提出同种抗原依赖性的初始移植损伤消退，但会引发后期事件：肾小球超滤、蛋白尿和肾小球硬化。因此，该模型在后期适合研究CAN的同种抗原非依赖性因素，且缺乏同种抗原依赖性过程的标志物。
