Unresolved questions of renal magnesium homeostasis

While the basic tenets of Mg handling by the mammalian kidney have been clearly outlined, Mg homeostasis in the body, the mechanism of extracellular fluid Mg regulation by the kidneys, and the regulation of intracellular Mg concentrations are largely unknown. Only a small fraction of total body Mg is present in the extracellular fluid and handled by the kidney, raising the question whether other organs, intestine, muscle and bone participate in Mg balance as well. In view of the tight regulation of Mg concentration in the plasma and the life-threatening derangements when plasma Mg concentration falls outside the physiological range it is surprising that a hormone responsible for general Mg homeostasis has not yet been identified. A hormone or factor which regulates tubular Mg reabsorption and hence renal Mg excretion is suspected, but it has not been found in any animal. Renal regulation of extracellular Mg involves filtration at the glomerulus and reabsorption in the proximal tubule and the thick ascending limb of the loop of Henle, where respectively, 30 and 60% of the filtered Mg load are reabsorbed. In the nongrowing individual the quantities of Mg excreted match the quantities absorbed from the gut. Mechanisms of tubular Mg transport are largely unknown for lack of understanding of Mg transport across epithelial cell membranes. The unexplored nature of Mg physiology can be attributed to analytical limitations. However, with the advent of a new Mg exchanger suitable for microelectrode work and with the use of Mg-sensitive dyes, Mg research is about to enter the renaissance period.