LONG-TERM KIDNEY ISOGRAFTS DEVELOP FUNCTIONAL AND MORPHOLOGIC CHANGESTHAT MIMIC THOSE OF CHRONIC ALLOGRAFT-REJECTION

Objective This study examined antigen-independent factors in the patho genesis of chronic rejection of organ transplants. Summary Background Data In addition to alloantigen-dependent events, antigen-independent factors can influence chronic rejection of organ allografts. Initial i njury, including early ischemia and acute rejection, may contribute. M ethods Kidney isografts were transplanted orthotopically into bilatera lly nephrectomized rat recipients and studied functionally, morphologi cally and immunohistologically, at serial intervals up to 72 weeks aft er transplantation. Controls included chronically rejecting kidney all ografts using a well-established model, non-nephrectomized and unineph rectomized animals with a native kidney that had undergone initial isc hemia and uninephrectomized rats whose remaining kidney had been manip ulated operatively. Results Allograft recipients developed progressive proteinuria after 12 weeks, with gradual renal failure ultimately lea ding to death. At the same time. morphologic changes, including progre ssive arteriosclerosis and glomerulosclerosis, tubular atrophy, and in terstitial fibrosis, developed. Immunohistologically, macrophages infi ltrated glomeruli during this period and cytokines became upregulated. Comparable changes occurred in isografts, but later, beginning after week 24 and progressing thereafter. The single ischemic kidney in unin ephrectomized controls also developed the same lesions; no comparable changes were noted in other control kidneys. Conclusions Antigen-indep endent functional and morphologic changes occur in long-term kidney is ografts that resemble those appearing considerably earlier in allograf ts that reject chronically. initial injury and extent of functioning r enal mass may be important factors for such late changes.