Kidney Medicine | 2021
Magnesium and Cardiovascular Disease in CKD: The Mysteries of a Humble Divalent Cation
Abstract
them essential for life, require magnesium as a cofactor. However, magnesium remains underappreciated clinically, particularly in nephrology, because concentrations are monitored and treated only in specific disease states such as torsades de pointes or preeclampsia. However, there has been an increase in epidemiologic research investigating the relationship between serum magnesium levels and outcomes (specifically cardiovascular outcomes), bringing renewed attention to this often “forgotten” electrolyte. Patients with chronic kidney disease (CKD) often have abnormal serum magnesium levels, in part from decreased kidney clearance. Serum magnesium accounts for only w0.3% of total-body magnesium, most of which is filtered by glomeruli. Approximately 15% to 20% of magnesium is reabsorbed by the proximal tubule. The specific mechanisms mediating this are not fully understood, and the absorption likely occurs by passive paracellular diffusion. The thick ascending limb is the primary site of magnesium reabsorption (w70%), again relying on paracellular reabsorption along a concentration gradient. Last, around 10% to 15% of magnesium is reabsorbed by the distal convoluted tubule through a channel complex of transient receptor potential cation channel subfamily M member 6 (TRPM6) and TRPM7 on the apical membrane. The driving force for magnesium reabsorption in the distal convoluted tubule is the negative cellular potential primarily generated by potassium diffusion out through the Kv1.1 channel on the apical membrane. In addition to direct kidney handling, magnesium balance within the kidney often changes as a result of indirect effects of medications (such as loop or thiazide diuretics and calcineurin inhibitors), parathyroid hormone, volume status, electrolyte derangements, and serum magnesium levels. Given the propensity for abnormal magnesium levels in patients with CKD, understanding how magnesium is regulated, as well as the implications of abnormal magnesium levels, is important. Observational studies of patients with CKD have identified that both hypoand hypermagnesemia are associated with poor outcomes. Clinical trials of magnesium supplementation (aside from magnesium-phosphorus binders) are limited. Overall, magnesium levels appear