Physiology of a Forgotten Electrolyte-Magnesium Disorders

Magnesium (Mg) is the second most common intracellular cation and the fourth most abundant element on earth. However, Mg is a frequently overlooked electrolyte and often not measured in patients. While hypomagnesemia is common in 15% of the general population, hypermagnesemia is typically only found in preeclamptic women after Mg therapy and in patients with ESRD. Mild to moderate hypomagnesemia has been associated with hypertension, metabolic syndrome, type 2 diabetes mellitus, CKD, and cancer. Nutritional Mg intake and enteral Mg absorption are important for Mg homeostasis, but the kidneys are the key regulators of Mg homeostasis by limiting urinary excretion to less than 4% while the gastrointestinal tract loses over 50% of the Mg intake in the feces. Here, we review the physiological relevance of Mg, the current knowledge of Mg absorption in the kidneys and the gut, the different causes of hypomagnesemia, and a diagnostic approach on how to assess Mg status. We highlight the latest discoveries of monogenetic conditions causing hypomagnesemia, which have enhanced our understanding of tubular Mg absorption. We will also discuss external and iatrogenic causes of hypomagnesemia and advances in the treatment of hypomagnesemia.