The pathogenesis of renal allograft rejection: an experimental investigation in sheep

Fifteen renal allografts and 5 autografts were placed into the necks of bilaterally nephrectomized sheep. Ten of the sheep with allografts were also treated with azathioprine (5 mg/kg) and prednisone(1.5 mg/kg) daily. There were no changes in the distribution of immunoglobulins or of beta lC globulin which could be associated with the rapid decline in glomerular filtration rate observed in untreated allografts after 2 d and in immunosuppressed allografts after 6 d. However, this functional decline was associated with the development of interstitial oedema, lymphocyte infiltration, swelling of tubular and glomerular cells, and necrosis of the outer two-thirds of the renal cortex. Thus the onset of progressive cortical ischaemia appears to be an important event leading to renal allograft failure in sheep.