Chapter 16 Magnesium

16.1 Mg homeostasis

99 % of total body Mg is held in bone and intracellular stores. Intake is around 10 mmoles per day; 50% excretion in the urine and 50% in stool.

Intestinal absorption is through paracellular and active transcellular (TRPM6, TRPM7) pathways.

Renal tubular reabsorption is through paracellular (claudin-dependent) pathways in the TALH (70%) and transcellular (EGF / TRPM6-dependent) transport in the DCT (10%).

16.2 Hypomagnesaemia

16.2.1 Consequences

  • ECG changes (mimics hyperK and then torsades)
  • hypocalcaemia (combination of impaired PTH secretion and peripheral PTH resistance)
  • hypokalaemia

16.2.2 Differential diagnosis of hypomagesaemia

GI losses PPIs
EtOH
malabsorption
vomiting / diarrhoea
renal losses diuretics (loop / thiazides)
genetic tubulopathies (see below)
aminoglycosides
CNIs
amphoterocin
cisplatin chemotherapy (long-lasting)
anti-EGF therapy
EtOH
osmotic diuresis
poorly-controlled diabetes
renal losses anti-claudin autoAbs (very rare!)
ICF shift hungry bone syndrome
re-feeding syndrome
insulin
pancreatitis
endocrine Conn syndrome
hyperPTH

16.2.3 Notes on specific causes

PPIs

Incidence of hypoMg with PPIs ~ 1% after 3 months. Mg wasting is through extra-renal pathways. PPIs cause hypoNa, hypoK, hypoMg, hypoPO4.


Inherited tubulopathies

  • antenatal Bartter
  • familial hypoMg with hypercalicuria and nephrocalcinosis (claudins 16 or 19 AR)
  • hypoMg with secondary hypocalcaemia (TRPM6 variants AR = mixed intestinal and renal defects = profound hypoMg)
  • ADTKD-HNF1b (GU tract malformation with MODY5 diabetes)
  • Gitelman
  • EAST

16.3 Investigations

First, distinguish between GI and renal losses with urinary [Mg]. In the context of hypomagnesaemia: UMgV > 1 mmol per day or FEMg > 2 – 3 % = renal loss.

Next, if renal losses, measure UCaV. If also high then likely TALH lesion; if isolated Mg-wasting then likely DCT lesion.


\[\begin{equation} \text{fractional excretion, }FE_{Mg} = \frac{U_{Mg}}{P_{Mg} \times 0.7} \times \frac{P_{Creat}}{U_{Creat}} \tag{16.1} \end{equation}\]

When calculating FEMg, divide the result by 0.7. This is because PMg is multiplied by 0.7 to account for protein binding; only 70% of circulating Mg is free and therefore able to be filtered; 30% is albumin-bound (Agus, 1999).