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. Thirty-three NZW rabbits received a single intravenous injection of 250 mg/kg bovine serum albumen (BSA) with or without endotoxin (5 micrograms/kg) on day 0. Groups of rabbits were given intramuscular CyA as follows: 15 mg/kg from day -2 to +8, or 25 mg/kg/day from day -20 to +3 or day 0 to 5. Signs of this renal injury were haematuria, transient proteinuria, glycosuria and oliguria and they occurred during the rapid phase of antigen elimination when immune complexes were being formed. Seventeen of the 33 rabbits developed glomerular capillary thrombi and 11 of 17 also had glomerular and tubular infarction. Electron microscopic examination showed that these lesions were associated with severe endothelial injury and platelet-fibrin-leucocyte thrombi. These changes were more severe in the groups given 25 mg/kg. The lesions were not seen in untreated rabbits and 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 haemolytic uraemic syndrome. The model we describe may be valuable for the study of the mechanisms of endothelial injury and thrombosis in the kidney.