From the Guidelines
Thiazide diuretics are recommended to decrease urinary calcium excretion, making them useful for treating hypercalciuria and preventing calcium-containing kidney stones. Unlike other diuretics that increase calcium excretion, thiazides (such as hydrochlorothiazide, chlorthalidone, and indapamide) promote calcium reabsorption in the distal convoluted tubule of the kidney, as supported by the American College of Physicians guideline 1. This occurs through two main mechanisms: direct enhancement of calcium reabsorption in the distal tubule and indirect effects from volume contraction that increases proximal tubule calcium reabsorption.
The American Urological Association guideline also recommends offering thiazide diuretics to patients with high or relatively high urine calcium and recurrent calcium stones, with a Grade B evidence strength 1. Typical doses for this effect include hydrochlorothiazide 25-50 mg daily or chlorthalidone 12.5-25 mg daily. The hypocalciuric effect begins within days of starting therapy and persists during long-term treatment.
Some key points to consider when prescribing thiazides for this purpose include:
- Monitoring for potential side effects including hypokalemia, hyperuricemia, and glucose intolerance, which may require supplementation or dose adjustments
- Dietary prescription, especially restriction of sodium intake, should be continued when thiazides are prescribed, in order to maximize the hypocalciuric effect and limit potassium wasting, as recommended by the American Urological Association guideline 1
- Potassium supplementation (either potassium citrate or chloride) may be needed when thiazide diuretics are prescribed, as noted in the guideline 1.
Overall, thiazide diuretics are a valuable treatment option for patients with recurrent calcium stones, idiopathic hypercalciuria, or those at risk for osteoporosis, due to their ability to decrease urinary calcium excretion, as supported by the evidence from the American College of Physicians guideline 1 and the American Urological Association guideline 1.
From the FDA Drug Label
Hydrochlorothiazide also decreases the excretion of calcium Calcium excretion is decreased by thiazides
The effect of thiazide diuretic on urine calcium is a decrease in calcium excretion. This is a direct effect of thiazide diuretics, including hydrochlorothiazide, as stated in the drug label 2 and 2.
- Key points:
- Thiazide diuretics decrease calcium excretion
- This effect can lead to changes in parathyroid function and may cause hypercalcemia and hypophosphatemia in some patients
- Patients on prolonged thiazide therapy should be monitored for these potential effects 2
From the Research
Effect of Thiazide Diuretic on Urine Calcium
- Thiazide diuretics can decrease calcium excretion in the urine, leading to hypocalciuria 3.
- The reduction of hypercalciuria is observed in patients treated with hydrochlorothiazide and amiloride, suggesting that thiazide diuretics can suppress parathyroid hyperfunction 4.
- Thiazide diuretics affect renal calcium handling by increasing calcium reabsorption, which can lead to a decrease in urine calcium levels 5.
- However, thiazide diuretics can also cause hypercalcemia in some patients, especially those with primary hyperparathyroidism, by unmasking normocalcaemic or mild primary hyperparathyroidism 5, 6.
- The use of thiazide diuretics may have a beneficial role in the diagnosis of patients with concomitant hyperparathyroidism and hypercalciuria by distinguishing secondary hyperparathyroidism caused by hypercalciuria from normocalcaemic primary hyperparathyroidism 5.
Clinical Implications
- Patients on thiazide diuretics should have their electrolytes frequently checked, especially patients on calcium supplements, to monitor for hypercalcemia 6.
- Thiazide diuretics may have a role in managing patients with primary hyperparathyroidism who have an indication for parathyroidectomy in view of significant hypercalciuria, but are unfit for surgery 5.
- The effect of thiazide diuretics on parathyroid hormone secretion is controversial, and further studies are needed to fully understand their impact on calcium homeostasis 5.