Focal glomerulosclerosis and nephron atrophy in rats on long-term cyclosporine treatment

Although acute cyclosporine nephrotoxicity has been extensively studied both in humans and in experimental animals, little has been written about experimentally-induced chronic renal changes after cyclosporine treatment. Groups of rats were therefore given cyclosporin A (CyA), 10 mg/kg pelleted food, for 21, 32 and 66 weeks. This corresponds to a daily CyA dose of 5-6 mg/kg body weight which is comparable to both the minimal immunosuppressive dose in rats and the doses given to patients. Kidney tissue was investigated using light microscopic morphometry and electron microscopy. After 32 wk, mild renal lesions in the form of focal glomerulosclerosis and nephron atrophy were present in the CyA-treated animals but nearly absent in the controls (p less than 0.05). At 66 wk, the changes were extensive in the CyA-treated animals. Similar but much less pronounced changes known as "chronic nephropathy of the rat" were found in the untreated rats. The proportion of glomeruli with segmental lesions was 33% in the CyA-treated animals and 7.5% in the controls (p = 0.014). No significant vascular lesions were found in either group. Electron microscopy confirmed the light microscopic observations but no ultrastructural changes specific for CyA treatment were identified. In conclusion, as with humans, chronic irreversible renal lesions can be induced in the rat by administering moderate doses of CyA over a long period.