Clinical implications of disordered magnesium homeostasis in chronic renal failure and dialysis

Magnesium (Mg) is the fourth most abundant cation in the body, mainly located within bone and skeletal muscle. The normal total plasma Mg concentration varies in a narrow range, with approximately 60% present as free Mg ions, the biologically active form. The kidney plays a principal role in Mg balance. Approximately 70-80% of plasma Mg is ultrafilterable, and under normal circumstances, 95% of the filtered load of Mg is reabsorbed. As chronic renal failure (CRF) progresses, urinary Mg excretion may be insufficient to balance intestinal Mg absorption and dietary Mg intake becomes a major determinant of serum and total body Mg levels. Until severe reductions in glomerular filtration rate (<30 ml/min), serum Mg levels are usually normal; with lower rates of renal function, serum Mg is increased. Concerning dialysis patients, dialysate Mg plays a critical role in maintaining Mg homeostasis, with serum Mg being largely dependent on the concentration of the ion in the dialysis solution. Magnesium has been implicated in diverse consequences, both beneficial and deleterious, in patients with CRF and dialysis. Potential harmful effects of elevated Mg include altered nerve conduction velocity, increased pruritus, and alterations to osseous metabolism and parathyroid gland function (mineralization defects, contribution to osteomalacic renal osteodystrophy, and adynamic bone disease). Hypermagnesemia also may retard vascular calcification. Low Mg levels have been associated with impairment of myocardial contractility, intradialytic hemodynamic instability, and hypotension. In addition, low Mg has been also linked to carotid intima-media thickness, a marker of atherosclerotic vascular disease and a predictor of vascular events.