[Chronic allograft nephropathy: its diagnosis and treatment].
The process of chronic allograft nephropathy (CAN) is primarily concerned with disparity in major histocompatibility. However, changes similar to CAN have been seen in human kidney transplants between identical twins, as well as in rat kidney isografts. Such changes cannot be explained by antigen-dependent factors; antigen-independent factors are likely to be involved in the onset of CAN. A CAN-type picture also was seen in a rat single kidney model subjected to ischemic injury, indicating the importance of ischemia in the process of CAN. In the present study, CAN was accelerated by renal ablation in a rat kidney transplant model with reduced nephron number. Conversely, recipients with increased renal mass bearing two allografts, did not show any signs of CAN. These observations suggested that a non-allogenic factor such as ischemia and insufficient nephron number is critical in the development of CAN, and thus the etiology of CAN is hypothesized as follows. Many factors such as ischemic injury, acute rejection or infection reduce the functioning nephron number, which causes hyperfiltration in remaining nephrons leading to glomerulosclerosis. This in turn, further reduces the functioning nephron number. These progressive events may reinforce further the stimulus of hyperfiltration, thereby establishing a self-sustaining vicious cycle. Any factor preventing the reduction of functioning nephron number, can be a candidate for treatment. Herein, we showed that treatment with hepatocyte growth factor (HGF), a renotropic factor, in the initial disease stage prevented further development of CAN.
Azuma
Haruhito
H
Department of Urology, Osaka Medical College.
D000818:Animals; D002908:Chronic Disease; D006084:Graft Rejection / Q000209:etiology* / Q000628:therapy; D006085:Graft Survival; D017228:Hepatocyte Growth Factor / Q000235:genetics; D016030:Kidney Transplantation; D008285:Major Histocompatibility Complex; D051381:Rats; D011916:Rats, Inbred F344
D017228:Hepatocyte Growth Factor