These authors contributed equally to this study.
Ultrastructural analysis of the Fisher to Lewis rat model of chronic allograft nephropathy
Article first published online: 9 JUN 2005
Volume 18, Issue 7, pages 863–870, July 2005
How to Cite
Hamar, P., Lipták, P., Heemann, U. and Iványi, B. (2005), Ultrastructural analysis of the Fisher to Lewis rat model of chronic allograft nephropathy. Transplant International, 18: 863–870. doi: 10.1111/j.1432-2277.2005.00146.x
- Issue published online: 9 JUN 2005
- Article first published online: 9 JUN 2005
- Received: 20 October 2004 Revision requested: 2 December 2004 Accepted: 15 March 2005
- chronic allograft nephropathy;
- Fischer-to-Lewis rat model;
- T-cell cytotoxicity;
- transplant arteriopathy;
- transplant capillaropathy;
- transplant glomerulopathy
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.