Physiology of a Forgotten Electrolyte-Magnesium Disorders

Magnesium (Mg²⁺) is the second most common intracellular cation and the fourth most abundant element on earth. However, Mg²⁺ 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 Mg²⁺ 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 Mg²⁺ intake and enteral Mg²⁺ absorption are important for Mg²⁺ homeostasis, but the kidneys are the key regulators of Mg²⁺ homeostasis by limiting urinary excretion to less than 4% while the gastrointestinal tract loses over 50% of the Mg²⁺ intake in the feces. Here, we review the physiological relevance of Mg²⁺, the current knowledge of Mg²⁺ absorption in the kidneys and the gut, the different causes of hypomagnesemia, and a diagnostic approach on how to assess Mg²⁺ status. We highlight the latest discoveries of monogenetic conditions causing hypomagnesemia, which have enhanced our understanding of tubular Mg²⁺ absorption. We will also discuss external and iatrogenic causes of hypomagnesemia and advances in the treatment of hypomagnesemia.