GLOMERULAR THROMBOSIS AND CORTICAL INFARCTION IN CYCLOSPORIN-TREATED RABBITS WITH ACUTE SERUM SICKNESS

Abstract

Rabbits given acute serum sickness (ASS) and treated with cyclosporin A (CyA) developed glomerular capillary thrombosis and cortical infarction, lesions not seen in unmodified ASS. NZW rabbits (33) received a single i.v. injection of 250 mg/kg bovine serum albumin (BSA) with or wihtout endotoxin (5 .mu.g/kg) on day 0. Groups of rabbits were given i.m. CyA as follows: 15 mg/kg per day form day -2 to +8, or 25 mg/kg per day from day -2 to +3 or day 0 to 5. Signs of this renal injury were hematuria, transient proteinuria, glycosuria and oliguria and they occurred during the rapid phase of antigen elimination when immune complexes were being formed. Of the 33 rabbits, 17 developed glomerular capillary thrombi and II of the 17 also had glomerular and tubular infarction. EM examination showed that these lesions were associated with severe endothelial injury and platelet-fibrin-leukocyte thrombi. These changes were more severe in the groups given 25 mg/kg. The lesions were not seen in untreated rabbits with ASS, nor in normal rabbits given equivalent doses of CyA alone. A strikingly similar renal lesion has been seen in patients receiving CyA following bone marrow transplantation and also in the hemolytic uremic syndrome. The model described may be valuable for the study of the mechanisms of endothelial injury and thrombosis in the kidney.