Ionized and Total Magnesium Levels in Cyclosporin-Treated Renal Transplant Recipients: Relationship with Cholesterol and Cyclosporin Levels

1. Ionized magnesium, measured using a newly developed ion-selective electrode, total magnesium, and ionized and total calcium were evaluated in 39 stable, long-term, cyclosporin-treated renal transplant recipients and compared with those of age-matched, non-transplanted control subjects. Total cholesterol, cyclosporin trough level, serum creatinine, time after-transplant and the ratio of ionized calcium to ionized magnesium were also measured in renal transplant recipients and the relationships between these variables and ionized and total magnesium were evaluated. 2. Renal transplant recipients exhibited marked deficits in ionized magnesium, with a mean value of 0.54 ±0.01 mmol/l as compared with 0.61 ± 0.006 mmol/l for normal control subjects (P ≦ 0.05), with a more moderate deficit in total magnesium. Values for ionized and total calcium did not differ. By stepwise linear multiple regression analysis, ionized magnesium was significantly related to cyclosporin trough level and total cholesterol but not to serum creatinine, time after transplant or the dose of cyclosporin. Ionized magnesium correlated inversely with cyclosporin trough level and directly with total cholesterol. The ratio of ionized calcium to ionized magnesium was elevated in renal transplant recipients when compared with control subjects and correlated positively with the cyclosporin trough level. 3. Deficits in ionized magnesium are common during the late post-transplant period in cyclosporin-treated renal transplant recipients. Ionized magnesium may be a more sensitive clinical parameter than total magnesium in this population, in whom total magnesium may be only mildly decreased in the setting of a severe deficit in ionized magnesium. 4. Ionized magnesium correlates with the cyclosporin level. Renal transplant recipients with high cyclosporin levels demonstrate the most severe deficits in ionized magnesium, and this finding could contribute to cyclosporin-induced hypertension and nephrotoxicity. The direct correlation between ionized magnesium and total cholesterol may result from a ‘masked magnesium deficiency’, as has been suggested in animal models, and requires further study. 5. Accelerated atherosclerosis observed after renal transplantation may relate to alterations in ionized magnesium and elevated ratios of ionized calcium to ionized magnesium, which are associated with atherogenesis in other models.