Novel molecular pathways in renal Mg2+ transport: a guided tour along the nephron

This review highlights recent advances in renal magnesium (Mg) handling. The understanding of the molecular processes of epithelial Mg transport has expanded considerably due to the identification of novel genes involved in hypomagnesemic disorders.

Mg deficiency remains one of the most common electrolyte disorders. Detailed genetic analysis of families with inherited forms of hypomagnesemia has led to the identification of new genes involved in Mg homeostasis. As such, familial hypomagnesemia has been linked to mutations in the claudin-16/19 complex located in the thick ascending limb. Moreover, the pro-epidermal growth factor, the potassium channels Kv1.1 and Kir4.1, and the hepatocyte nuclear factor 1B have recently been identified as causative factors in syndromes of hereditary hypomagnesemia. These proteins play key roles in regulating electrolyte balance within the distal convoluted tubule, either by directly affecting the epithelial Mg channel, transient receptor potential channel melastatin member 6, or by altering the driving force for Mg influx via the channel.

Recent genetic and molecular studies have further elucidated the processes that govern renal Mg transport and hence systemic Mg balance. This has provided us with new tools to understand the molecular pathology behind hypomagnesemia.