Renal handling of magnesium: drug and hormone interactions

Abstract

Magnesium is the fourth most abundant cation in the human body and the second most common cation in the intracellular fluid. The abundance and distribution of this divalent cation implies an essential role of magnesium in intracellular metabolism. Although no single homeostatic control has been demonstrated for magnesium, the cellular availability of this cation is closely regulated by the gastrointestinal tract, kidney and bone. The purpose of this review is to survey some of the events involved in renal magnesium handling. The excretory side of magnesium balance involves appropriate changes in renal magnesium handling. Present evidence suggests that the renal handling of magnesium is normally a filtration-reabsorption process. Experimental support for secretion remains unconvincing. Renal magnesium reabsorption has distinctive features when compared with that of sodium and calcium. The concentration of magnesium in the proximal tubule rises 1.5 times greater than the glomerular filtrate. Some 20-30% of the filtered magnesium is reabsorbed in the proximal tubule compared to the fractional absorption of sodium or calcium of 50-60%. Although the fractional reabsorption of magnesium is only half that of sodium, it changes in parallel with that of sodium in response to changes in extracellular fluid volume. The major portion of filtered magnesium (some 65%) is reabsorbed in the loop of Henle, mainly in the thick ascending limb. Recent evidence suggests that magnesium reabsorption in the ascending limb may be voltage-dependent and secondary to active sodium chloride reabsorption. Evidence also suggests an important competition between magnesium and calcium for transport at the basolateral surface of the ascending limb cell. The loop of Henle appears to be the major nephron site where magnesium reabsorption is controlled. The principal factors which alter magnesium reabsorption in the loop include parathyroid hormone, changes in plasma magnesium and calcium concentration and the loop diuretics. About 10% of the filtered magnesium is delivered into the distal nephron where only a small fraction of the filtered magnesium is reabsorbed and the transport capacity is readily exceeded with increased magnesium delivery. A number of drugs have been shown to alter magnesium handling; these include antibiotics such as gentamicin, antineoplastic agents such as cisplatin and immunological suppressive drugs such as cyclosporin. The cellular alterations of these diverse drugs leading to renal magnesium wasting are not well understood.