Cyclosporine A-induced alterations in magnesium homeostasis in the rat

The immunosuppressive drug cyclosporine A (CsA) exhibits significant nephro toxicity. Disturbance of magnesium (Mg) homeostasis may be an important com ponent of this nephrotoxicity. It has been suggested that transmigration of Mg from plasma to tissues may be an important component of CsA-induced alt erations in Mg homeostasis. In this study, CsA nephrotoxicity in male Wista r rats was investigated and alterations in Mg homeostasis along with other indices of toxicity were assessed. Animals were dosed daily for 14 days i.p . with CsA (20 mg/kg body weight). Control animals received vehicle alone, CsA toxicity was evidenced by i) lower gain in body weight, ii) reduced thy mus/body weight ratio, iii) increased blood urea nitrogen and creatinine, i v) a tendency for reduced plasma magnesium and v) increased urinary Mg excr etion and greatly increased fractional excretion of Mg. Tissue Mg analysis did not reveal any changes in thymus or skeletal muscle Mg while Mg in kidn ey tissue tended to be reduced. Electron microscopy revealed some damage in renal tubules of rats treated with cyclosporine including translucent cyto plasm, vacuolization, rounded and swollen mitochondria, damage to brush bor der and disruption of basal infoldings. These results indicate that direct renal tubular damage may result from CsA exposure. No evidence was found fo r CsA-induced movement of Mg from plasma to tissues. CsA-induced altered re nal handling of Mg and this renal Mg wasting may be an important consequenc e of the nephrotoxicity.