What type of kidney disorders lead to hypomagnesemia?
Kidney magnesium losses are increased with increased urine output. This occurs with diuretics, osmotic diuresis (as seen in diabetes), excessive intravenous saline, postobstructive diuresis, the recovery phase of acute tubular necrosis (ATN), and following a kidney transplant.
Loop diuretics specifically disrupt the NaK2Cl channel needed to generate the positive tubular lumen charge that drives magnesium and calcium reabsorption in the TAH. Thiazide diuretics induce hypomagnesemia by preventing the distal absorption of magnesium.
Hypercalcemia increases kidney magnesium wasting through a mechanism similar to that of loop diuretics. The cells of the TAH have a calcium-sensing receptor (CaSR) on the basolateral membrane. When activated, the CaSR antagonizes the ROMK channel, preventing the generation of the positive luminal charge that drives magnesium reabsorption.
A number of other drugs can cause hypomagnesemia through increased kidney loss of magnesium, including:
- a. Aminoglycosides
- b. Amphotericin B
- c. Pentamidine
- d. Cisplatin
- e. Epidermal growth factor (EGF) monoclonal antibodies
- f. Calcineurin inhibitors
Chronic ethanol abuse causes a kidney magnesium leak. It can take weeks of abstinence to reverse this injury. In addition to the kidney leak, these patients often have poor dietary magnesium and increased GI losses, which contributes to the hypomagnesemia.
There are numerous inherited magnesium wasting nephropathies; none of them are common. The two most well known are Gitelman syndrome and Bartter syndrome.
Gitelman syndrome is an autosomal recessive disorder resulting from an inactivating mutation of the thiazide-sensitive sodium chloride cotransporter gene (NCCT) of the distal convoluted tubules. These patients present with signs and symptoms of chronic thiazide ingestion, including mild salt wasting, volume depletion, hypokalemia, metabolic alkalosis, and hypomagnesemia.
Bartter syndrome is a kidney sodium wasting nephropathy that mimics chronic loop diuretic use. It is typically autosomal recessive, though there is an autosomal-dominant form. Patients typically have low blood pressure, hypokalemia, metabolic alkalosis, hypocalcemia, and hypomagnesemia. The hypomagnesemia tends to be less severe than that seen in Gitelman syndrome.