What is the role of thiazides in the treatment of hypercalciuria?

Updated: Jun 02, 2021
  • Author: Stephen W Leslie, MD, FACS; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Thiazides are currently the mainstay of medical therapy for hypercalciuria. These agents do not directly affect intestinal calcium absorption but instead stimulate calcium reabsorption in the distal renal tubule. In addition, thiazides decrease extracellular fluid volume and increase proximal renal tubular calcium reabsorption. They generally lower urinary calcium levels by about one third, but reductions of as much as 50% or 400 mg/day have been reported. (Their hypocalciuric effect is reduced, however, if sodium intake is not limited.) [43]

Even when used in a nonselective fashion, thiazides can reduce stone recurrences from 50% (untreated) to 20% (treated) over 5 years. Thiazides are particularly well suited for hypercalciuric patients with hypertension, especially when dietary control measures alone fail to adequately normalize urinary calcium excretion.

Renal leak hypercalciuria

Thiazides are specifically indicated for renal leak hypercalciuria, in which case they not only reduce the inappropriate renal calcium loss but also lower PTH levels and correct other metabolic problems. When used appropriately in renal leak hypercalciuria, thiazides prevent secondary hyperparathyroidism and normalize vitamin D3 synthesis, calcium absorption, and urinary calcium excretion. Stone formation rates drop more than 90% in patients with renal calcium leak who are placed on long-term thiazide therapy.

Absorptive hypercalciuria

When used for absorptive hypercalciuria, thiazides are still effective, but their long-term usefulness may diminish over time as the bone stores become filled, allowing the hypercalciuria to return. Until then, bone density on thiazide therapy has been shown to increase by about 1.5% or more per year. When thiazides lose their hypocalciuric effect, which has been reported to occur, on average, about 2 years after therapy initiation, the use of an alternate regimen for a period of approximately 6 months usually restores the efficacy of the thiazide medication for use in hypercalciuria.

Other thiazide effects

Thiazides have many other effects on the body. These drugs increase serum calcium and uric acid levels while decreasing urinary citrate levels. Hyperuricemia and acute gout rarely develop in individuals receiving thiazides.

However, adverse effects occur in about one third of patients, although they are usually mild. For example, a risk of hypokalemia, hyponatremia, hypocitraturia, and magnesium loss, as well as of cholesterol level increase, exists. Moreover, thiazides tend to increase urinary volume because of their diuretic effect, a useful feature in kidney stone formers but one that can also easily lead to dehydration if oral fluid intake is not maintained.

The most bothersome clinical adverse effect is lethargy, but muscle aches, depression, decreased libido, generalized weakness, and malaise also can occur. About 20% of patients stop thiazide therapy because of these adverse effects.

Chemically, thiazides are sulfonamides and generally should not be used or should be used cautiously in patients with a history of sulfa allergy. Drug interactions have been reported when thiazides are used together with alcohol, barbiturates, narcotics, antidiabetic drugs, steroids, pressor amines, muscle relaxants, lithium, and nonsteroidal anti-inflammatory agents (NSAIDs).

Most patients on thiazides do not need any potassium supplementation, but potassium and electrolyte levels need to be checked periodically. Because of the risk of hypokalemia and hypocitraturia, potassium citrate supplements are often prescribed along with thiazides in calcium-stone formers.

Thiazide dosing

Thiazide dosage depends on the specific medication used. Once-a-day drug preparations are usually preferred because of better patient compliance and tolerability. Trichlormethiazide (Naqua) is administered as a 2- or 4-mg daily tablet. Indapamide (Lozol) can be administered in either 1.25- or 2.5-mg doses once a day. [44]

If a potassium-sparing combination is desired, those that contain triamterene, such as Dyazide, should be avoided, because triamterene can form its own stones. Moduretic, which uses amiloride as a potassium-sparing diuretic, would be recommended. Amiloride does not form stones and has a mild hypocalciuric effect of its own.

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