Does Hydrochlorothiazide (HCTZ) increase calcium levels?

Effect of Hydrochlorothiazide (HCTZ) on Calcium Levels

Yes, hydrochlorothiazide (HCTZ) increases serum calcium levels by decreasing urinary calcium excretion, with this effect being more pronounced in patients with elevated parathyroid hormone levels.

Mechanism of Action

HCTZ affects calcium metabolism through several mechanisms:

1. Direct renal effects:

   • HCTZ decreases the excretion of calcium in the urine 1
   • It blocks sodium and chloride reabsorption in the distal tubule, which secondarily enhances calcium reabsorption

2. Parathyroid hormone interaction:

   • The hypocalciuric effect appears to be enhanced in patients with elevated PTH levels
   • In anuric patients on hemodialysis, HCTZ increased serum calcium primarily in those with PTH levels >300 pg/ml, suggesting an extra-renal mechanism that is PTH-dependent 2

Clinical Evidence

• A single 50 mg dose of HCTZ has been shown to:

  • Decrease urinary calcium excretion (UCaV)
  • Decrease calcium clearance (CCa)
  • Decrease fractional excretion of calcium (FECa)
  • Increase total serum calcium and ionized calcium concentrations 3

• Patients with renal hypercalciuria (with secondary hyperparathyroidism) show exaggerated natriuretic and calciuric responses to HCTZ compared to normal subjects 4

• The FDA drug label explicitly states that "hydrochlorothiazide decreases the excretion of calcium and uric acid" 1

Clinical Implications

1. Therapeutic applications:

   • HCTZ can be used therapeutically in patients with hypercalciuria to reduce calcium excretion 5
   • It may be beneficial in preventing calcium-containing kidney stones

2. Monitoring considerations:

   • Patients on HCTZ should have calcium levels monitored, particularly those with:
     • Pre-existing hypercalcemia
     • Parathyroid disorders
     • Chronic kidney disease

3. Special populations:

   • In patients with chronic kidney disease, HCTZ may contribute to calcium-phosphorus imbalance
   • The KDOQI guidelines recommend maintaining serum calcium levels in the target range (8.4 to 9.5 mg/dL) 6
   • In patients with X-linked hypophosphatemia, thiazide diuretics like HCTZ may decrease calciuria 6

Potential Risks and Considerations

• HCTZ simultaneously affects other electrolytes:

  • Increases fractional excretion of magnesium (FEMg)
  • Decreases serum magnesium concentrations
  • Decreases phosphate clearance and increases serum phosphate 3

• In patients with kidney disease, the calcium-raising effect of HCTZ may contribute to vascular calcification if not properly monitored

• The calcium-phosphorus product should be maintained at <55 mg²/dL² in patients with chronic kidney disease 6

Clinical Management

For patients requiring HCTZ therapy:

1. Measure baseline calcium levels before initiating therapy
2. Monitor serum calcium periodically, especially in high-risk patients
3. Consider dose adjustment or alternative medications if hypercalcemia develops
4. Pay attention to concurrent medications that might affect calcium levels

For patients developing hypercalcemia on HCTZ:

1. Consider discontinuing HCTZ and switching to a loop diuretic if diuresis is still required
2. Evaluate for other causes of hypercalcemia
3. Monitor calcium levels until normalization

In summary, HCTZ has a well-documented effect of increasing serum calcium levels primarily through decreased urinary calcium excretion, with this effect potentially enhanced by PTH activity.