Cyclosporine A nephrotoxicity: evidence for mesangial foam-cells in dogs

Nephrotoxicity of cyclosporine A was studied in dog after 3 weeks' administration of the drug at high doses (20 mg/kg/day). Cyclosporine A concentrations measured in different organs revealed a high ratio between renal tissue and plasma. Renal histopathology showed non-specific tubular lesions and glomerular modifications. There were lipids in the mesangial cells which took on a foamy aspect. Ultrastructural study and lipid staining confirmed these findings, and non-specific esterase reaction revealed no macrophagic infiltration. Using anti-CSA antibodies it was not possible to demonstrate CSA in the mesangial cells. This alteration has never been described before in CSA therapy and its meaning is not clear; however, it does suggest that there occur modifications in the lipid metabolism or in the phagocytic function of the mesangial cells when cyclosporine A is administered over long periods.