What are the causes of hypomagnesemia in various patient populations, including older adults, critically ill patients, and those with underlying medical conditions such as chronic kidney disease, diabetes, and gastrointestinal disorders?

Causes of Hypomagnesemia

Primary Mechanisms of Magnesium Loss

Hypomagnesemia results from three main mechanisms: inadequate intake, excessive gastrointestinal losses, or increased renal wasting—with renal losses being the most common cause in hospitalized patients. 1, 2

Gastrointestinal Causes

Reduced Intake and Absorption:

• Protein-calorie malnutrition and prolonged administration of magnesium-free IV fluids or total parenteral nutrition 1
• Chronic watery diarrhea and steatorrhea causing direct magnesium loss through intestinal fluid (approximately 100 mmol/L sodium with substantial magnesium) 3
• Short bowel syndrome, particularly with jejunostomy, where each liter of stomal output contains significant magnesium 3
• Bowel fistulas and continuous nasogastric suctioning 1
• Malabsorption syndromes and bowel resection/bypass 4
• Primary familial magnesium malabsorption (rare genetic disorder) 1

Critical Pitfall: In patients with high-output diarrhea or stomas, sodium and water depletion triggers secondary hyperaldosteronism, which paradoxically increases renal magnesium wasting despite total body depletion—making rehydration with IV saline the crucial first step before magnesium supplementation. 3

Renal Causes

Genetic Tubular Disorders:

• Bartter syndrome (types 1-5), characterized by hypokalemia, metabolic alkalosis, renal magnesium wasting, and hypercalciuria 5, 2
• Gitelman syndrome, distinguished from Bartter by hypocalciuria rather than hypercalciuria 2
• Familial renal magnesium wasting with hypercalciuria, nephrocalcinosis, and nephrolithiasis 2

Acquired Renal Losses:

• Loop diuretics (furosemide) and thiazide diuretics, which inhibit sodium chloride transport in the ascending loop of Henle and distal convoluted tubule respectively 2, 3
• Post-obstructive diuresis and post-acute tubular necrosis 1
• Renal transplantation and interstitial nephropathy 1

Medication-Induced Renal Wasting:

• Aminoglycosides (gentamicin), amphotericin B, and cisplatin causing direct tubular toxicity 1, 6
• Proton pump inhibitors causing chronic renal magnesium wasting 7
• Calcineurin inhibitors (cyclosporine, tacrolimus) in transplant patients 7
• Pentamidine and foscarnet 1

Redistribution and Metabolic Causes

Cellular Redistribution:

• Exchange transfusion and acute pancreatitis 4
• Refeeding syndrome in malnourished patients, where magnesium shifts intracellularly during nutritional repletion 3
• Epinephrine administration, cold stress, and stress from serious injury or extensive surgery causing acute hypomagnesemia 8

Endocrine and Metabolic Disorders:

• Diabetes mellitus (combination of poor intake, osmotic diuresis, and medication effects) 1
• Hypercalcemia and hyperthyroidism increasing renal magnesium excretion 4
• Primary aldosteronism 4

Special Populations

Alcoholism:

• Multiple contributing factors including poor nutrition, chronic diarrhea, vomiting, and direct renal tubular effects 1
• Often presents with the classic triad of hypomagnesemia, hypokalemia, and hypocalcemia 9

Critically Ill Patients:

• Hypomagnesemia occurs in 60-65% of patients undergoing continuous renal replacement therapy (CRRT) 3, 9
• Regional citrate anticoagulation during CRRT increases magnesium losses through chelation of ionized magnesium by citrate 3, 7

Older Adults:

• Reduced dietary intake, polypharmacy (especially diuretics and proton pump inhibitors), and age-related decline in renal function 3

Diagnostic Approach

Fractional Excretion of Magnesium:

• Fractional excretion <2% indicates appropriate renal conservation, suggesting gastrointestinal losses 2
• Fractional excretion >2% in patients with normal kidney function indicates inappropriate renal magnesium wasting 2

Urinary Calcium-Creatinine Ratio:

• Hypercalciuria suggests Bartter syndrome, loop diuretics, or familial renal magnesium wasting 2
• Hypocalciuria suggests Gitelman syndrome or thiazide diuretics 2

Key Clinical Considerations

The serum magnesium level is a poor proxy for total body stores, as less than 1% of total body magnesium is present in blood—normal serum levels can coexist with significant intracellular depletion. 3, 4 Symptoms typically do not arise until serum magnesium falls below 1.2 mg/dL (0.5 mmol/L), with life-threatening ventricular arrhythmias being the most serious complication. 2, 6

Always suspect concurrent hypomagnesemia in patients with refractory hypokalemia or hypocalcemia, as magnesium deficiency causes dysfunction of multiple potassium transport systems and impairs parathyroid hormone release—these electrolyte abnormalities will not respond to direct replacement until magnesium is corrected. 3, 9, 10