Reappraisal of the Quantity and Nature of Renal Calcifications and Mineral Metabolism in the Magnesium-Deficient Rat

Abstract

There is an urgent need for drugs capable of inhibiting renal calcifications, nephrocalcinosis and stones included, in humans. Current anticalcification medication is based mainly on alkalinization of the metabolism using potassium-containing citrate alone, despite the fact that calcium stone patients suffer marginally from both magnesium and potassium deficiency. We investigated the anticalcification efficacy of oral potassium citrate versus the combined administration of this drug and magnesium citrate in the magnesium-deficient rat developing corticomedullary nephrocalcinosis and luminal microliths in the long term. Among other things we employed specific stains for calcium and oxalate, light microscopy and element analysis for renal tissue and calcifications, respectively. In addition, minerals in renal tissue, urine and plasma were determined, as well as the state of extracellular calcium homeostasis. Magnesium deficiency caused pure calcium phosphate tissue deposits, containing no magnesium, but no deposition of calcium oxalate in the tubular lumen; tissue magnesium, calcium and phosphorus were increased, and there was marked potassium wastage via urine; despite mild hypercalcemia other signs of hyperparathyroidism were not found. Alkalinization with the two kinds of medication evoked an increase in urinary pH, citrate, and potassium; however, potassium citrate alone tended to aggravate renal concretions, whereas the combination of this drug with magnesium citrate completely prevented concretions. It was concluded that: (1) magnesium deficiency-induced calcifications are oxalate-free and are not sensitive to mobilization by alkalinization with potassium citrate, which might explain the failure of the drug to prevent stone recurrence in clinical stone patients, and (2) the combination of potassium citrate and magnesium citrate, which shows enormous anticalcification efficacy, deserves high priority in clinical trials aimed at evaluating strategies for the prevention of stones.