What is the effect of Lasix (furosemide) on serum calcium levels?

Effect of Furosemide on Serum Calcium Levels

Furosemide increases urinary calcium excretion and can lead to hypocalcemia, particularly in patients with impaired calcium regulation or those on long-term therapy. 1

Mechanism of Action

Furosemide affects calcium homeostasis through several mechanisms:

1. Direct calciuretic effect:

   • Inhibits sodium and calcium reabsorption in the thick ascending limb of the loop of Henle
   • Increases urinary calcium excretion by 2-3 fold 2, 3
   • This effect persists during chronic administration and does not diminish over time 2

2. Compensatory mechanisms:

   • While the kidney develops compensatory mechanisms for sodium conservation after furosemide administration, these mechanisms do not extend to calcium conservation 2
   • The distal convoluted tubule attempts to increase calcium reabsorption by upregulating calcium transport molecules (TRPV5, TRPV6, calbindin-D28k) in response to increased calcium delivery 3

Clinical Implications

Risk of Hypocalcemia

Furosemide can cause hypocalcemia through several mechanisms:

• Increased urinary calcium loss: The FDA label specifically warns that "all patients receiving furosemide therapy should be observed for signs or symptoms of electrolyte imbalance including hypocalcemia" 1
• Symptoms of hypocalcemia may include tetany, muscle cramps, weakness, and cardiac arrhythmias 1
• Particularly concerning in specific populations:
  • Hypoparathyroid patients: Significant decreases in serum ionized calcium have been documented with furosemide use 4
  • Premature infants: Furosemide may precipitate nephrocalcinosis/nephrolithiasis 1

Monitoring Recommendations

For patients on furosemide therapy:

• Regular monitoring of serum calcium levels is essential, particularly during the initial stages of treatment 1
• Corrected calcium formula should be used in patients with altered albumin levels: Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 5
• Ionized calcium measurement may be more accurate in patients with altered protein levels 5

Long-term Effects

Chronic furosemide administration can have cumulative effects:

• Negative calcium balance: Long-term studies in growing rats showed that cumulative calcium balance was 7% lower in furosemide-treated animals compared to controls 2
• No evidence of stone formation: Despite marked hypercalciuria in animal models, there was no evidence of kidney stone formation 6

Management Considerations

For patients requiring furosemide who develop or are at risk for hypocalcemia:

1. Monitor serum calcium levels regularly during therapy 1
2. Consider thiazide diuretics as an adjunct therapy in cases of furosemide-induced hypercalciuria, as they can decrease calcium excretion 3
3. Calcium supplementation may be necessary in patients with persistent hypocalcemia 1
4. Careful monitoring in patients with hypoparathyroidism, as they are particularly susceptible to furosemide-induced decreases in ionized calcium 4

Conclusion

Furosemide has a significant calciuretic effect that can lead to hypocalcemia, particularly in vulnerable populations. Regular monitoring of calcium levels and appropriate interventions are essential to prevent complications related to calcium imbalance in patients receiving furosemide therapy.