Chapter 18 Magnesium
18.1 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%).
18.2 Hypomagnesaemia
18.2.1 Consequences
- ECG changes (mimics hyperK and then torsades)
- hypocalcaemia (combination of impaired PTH secretion and peripheral PTH resistance)
- hypokalaemia
18.2.2 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 |
18.2.3 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
18.3 Investigations
First, distinguish between GI and renal losses with urinary [Mg]. Remember that ideally FEMg is assessed on a fasting sample (2nd void).
In the context of hypomagnesaemia:
- renal losses = FE\(_Mg\) > 3%; UMgV > 1 mmol per day; UMgV/GFR > 15 mcmol/ml
- extra-renal losses = FE\(_Mg\) < 1%; UMgV/GFR < 5 mcmol/ml
Next, if renal losses, measure UCaV. If also high then likely TALH lesion; if isolated Mg-wasting then likely DCT lesion.
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).