Cyclosporin-induced hypomagnesaemia and renal magnesium wasting in rats

1. Twenty-four hour clearance studies were performed on three groups of rats to determine the hypomagnesaemic effect of cyclosporin. Group I rats served as controls, whereas group II rats received 10 mg of cyclosporin/kg and group III rats received 20 mg of cyclosporin/kg daily. 2. After 7 days of cyclosporin treatment, plasma magnesium concentration was 1.04 +/- 0.01 mmol/l in control rats compared with 0.85 +/- 0.01 mmol/l in group II and 0.81 +/- 0.02 mmol/l in group III. After 14 days of cyclosporin administration, group III rats developed severe hypomagnesaemia (0.67 +/- 0.01 mmol/l). This reduction in plasma magnesium was associated with an increase in the urinary excretion of magnesium. 3. This reduction in plasma magnesium and increment in magnesium excretion returned to normal 7 days after cessation of treatment. 4. Additional three-phase acute clearance experiments were performed on eight normal and 12 cyclosporin-treated rats (20 mg/kg). These animals were subjected to acute magnesium chloride infusion. After graded magnesium chloride infusion, despite a similar rise in plasma magnesium, the fractional magnesium excretion was significantly higher in the cyclosporin-treated animals. 5. Analysis of the fractional intestinal absorption of magnesium suggested that the development of hypomagnesaemia after cyclosporin treatment is due to magnesium loss by the kidney. Furthermore, this effect of cyclosporin on magnesium transport is only present during cyclosporin treatment and is reversible when treatment with cyclosporin is withdrawn.