Physiological and structural responses to chronic experimental renal allograft injury.
Chronic rejection necessitates a return to dialysis or retransplantation for a significant number of patients with renal allografts. Although alloresponses between donor organ and recipient importantly determine this process, the detailed immunologic processes and organ physiology of chronic rejection are unclear; in consequence its mechanism and therapy are uncertain. A model of chronic rejection in the rat was used to examine several facets of this process. Fisher-to-Lewis (F-L), allogeneic, and Lewis-to-Lewis (L-L), syngeneic, renal transplants were performed in nephrectomized recipients. All rats were treated with cyclosporin A (5 mg.kg-1.day-1) for 10 days from the time of grafting. At 6 wk, allogeneically grafted animals had a higher protein excretion rate (F-L, 47 +/- 30 mg/day; L-L, 17 +/- 6 mg/day; P < 0.05) and an increase in glomerular capillary pressure (F-L, 69 +/- 5 mmHg; L-L, 58 +/- 8 mmHg; P < 0.05) and fractional cortical interstitial volume (F-L, 29.8 +/- 4.3%; L-L, 19.5 +/- 4.0%; P < 0.01). This model of chronic rejection is characterized by glomerular capillary hypertension, proteinuria, and cortical interstitial expansion. Because these findings are also present in other models of chronic renal injury, mechanisms in addition to alloresponses may operate in chronic rejection.
Junaid
A
A
Department of Medicine, University of Minnesota, Minneapolis 55455.
Kren
S M
SM
Rosenberg
M E
ME
Nath
K A
KA
Hostetter
T H
TH
D000818:Animals; D001794:Blood Pressure; D002196:Capillaries; D016572:Cyclosporine / Q000627:therapeutic use; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology*; D007672:Kidney Cortex / Q000473:pathology; D007678:Kidney Glomerulus / Q000098:blood supply; D016030:Kidney Transplantation; D009392:Nephrectomy; D011507:Proteinuria; D051381:Rats; D011917:Rats, Inbred Lew; D017595:Renal Plasma Flow; D014184:Transplantation, Homologous
D016572:Cyclosporine