Functional and histologic characteristics of chronic renal allograft rejection.
Chronic allograft rejection very probably results from the interactions between allogeneic immune injury, tissue reactions in response to injury, and local intragraft hemodynamic adaptations to the progressive loss of functioning organ mass. We examined each of these components in a rat model of chronic renal allograft rejection. Although immunofluorescence studies of renal allografts with chronic rejection usually reveal nondiagnostic patterns of immunoglobulin deposits, we found, using Western blot analysis, donor-directed antibodies against novel glomerular basement membrane antigens in the sera of animals with chronic rejection-associated transplant glomerulopathy. Stop-flow micropuncture studies have shown that the glomerular capillary pressure in transplanted kidneys resembles that of the donor strain kidney in response to renal ablation. Northern blots for growth factor transcripts showed induced expression of mRNA levels for various growth factors in long-surviving renal transplants. Reduction in intraglomerular pressure was associated with increased recipient survival, preservation of renal function, decreased amounts of proteinuria, and less severe structural lesions in the glomeruli. We conclude that the glomerular lesions of chronic rejection may arise from a combination of antiglomerular (allo) antibodies in conjunction with increased intraglomerular pressures and local production of growth factors. The vascular lesions and interstitial scarring of chronic rejection may arise from previous episodes of graft vasculitis and interstitial inflammation, respectively.
Paul
L C
LC
University of Toronto, St. Michael's Hospital, Ontario, Canada.
D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000276:immunology; D001485:Basement Membrane / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology*; D006133:Growth Substances / Q000032:analysis / Q000502:physiology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017597:Renal Blood Flow, Effective / Q000502:physiology
D000906:Antibodies; D006133:Growth Substances