MICROANGIOGRAPHIC STUDIES ON RENAL ALLOGRAFT REJECTION IN THE RABBIT

Abstract

A quantitative microangiographic study on renal allograft in rabbits was carried out to determine the pathogenesis of acute rejection and hyperacute rejection as well as the mechanisms of action of immunosuppressive drugs.
Renal transplantations were performed on 42 rabbits, and they were randomly divided into two groups consisting of 26 allografts without treatment (group I) and 16 with immunosuppressive drugs (group II).
Immunosuppressive regimens were given in daily doses of azathioprine 1mg/kg orally, cyclophosphamide 1mg/kg and methylprednisolone 0.5mg/kg subcutaneously, immediately after renal transplantation.
Another 12 rabbits, presensitized with multiple skin grafts before the renal allografts and developed hyperacute rejection, were put into group III.
Each kidney graft, excised after 2, 4, 8, 16, or 24 hours, or on the 2, 4, 6, 8, 10, 12 or 14th day after renal transplantation, was examined histologically and microangiographically, and the following results were obtained:
1) In group I, interstitial mononuclear cell infiltration began to appear 16 to 24 hours after transplantation and became more conspicuous with time. Severe interstitial nephritis was found after a week.
Interlobular arteries and, especially, afferent arterioles, were temporarily narrowed in caliber (inner diameter) on the 2nd day, but showed gradual progress toward recovery from the 6th day, microangiographically.
Such temporary vasoconstriction of afferent arterioles and interlobular arteries preceded the glomerular lesions and was considerd to be a first step of the functional disturbances in acute rejection.
2) In group II, the interstitial mononuclear cell infiltration and the temporary vasoconstriction of afferent arterioles and interlobular arteries occurred as in group I. However, subsequent changes at the glomerular level were distinctly prevented (p<0.01), leading to prolongation of the graft survival period.
This suggests that immunosuppressive drugs may prevent one of the processes, in which immune lymphocytes cause lesions of the capillary walls.
3) In group III, striking vasoconstriction of afferent arterioles (approx. 44% of the normal thickness) and interlobular arteries (approx. 58% of the normal thickness) appeared temporarily within two hours after renal transplantation, and gradually recovered to approximately normal caliber after 24 hours. The glomeruli, however, began to decrease in number 8 hours after transplantation (p<0.01), and appeared to give rise to vasoocclusion and microthrombosis in glomerular capillaries.
These findings suggest that vasoconstriction at the levels of interlobular arteries and afferent arterioles may be the main cause of the development of hyperacute rejection.