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Hypercalciuria increases the formation of calcium (calcium oxalate and calcium phosphate) stones, the most common types of kidney stone.  In patients with recurrent calcium nephrolithiasis, thiazide diuretics can help prevent stone formation by decreasing urine Ca²⁺ excretion.

Thiazides increase Ca²⁺ reabsorption through 2 major mechanisms:

1. Inhibition of the Na⁺/Cl⁻ cotransporter on the apical side of distal convoluted tubule cells decreases intracellular Na⁺ concentrations.  This activates the basolateral Na⁺/Ca²⁺ antiporter, which pumps Na⁺ into the cell in exchange for Ca²⁺.  The resulting decrease in intracellular Ca²⁺ concentration enhances luminal Ca²⁺ reabsorption across the apical membrane.
2. Hypovolemia induced by thiazides increases Na⁺ and H₂O reabsorption in the proximal tubule, leading to a passive increase in paracellular Ca²⁺ reabsorption.

(Choice A)  Acetazolamide is a carbonic anhydrase inhibitor that acts on the proximal convoluted tubule to cause bicarbonate wasting, raising urine pH and decreasing the risk of uric acid stones.  However, the resulting systemic acidosis may increase release of calcium phosphate from bone, which is then cleared by the kidneys.  Some studies have found that acetazolamide use may raise the risk of calcium stone formation.

(Choice B)  Ca²⁺ reabsorption in the loop of Henle occurs through both the transcellular and paracellular pathways.  Paracellular Ca²⁺ reabsorption depends on concurrent, transcellular Na⁺/K⁺/Cl⁻ reabsorption.  Loop diuretics (eg, furosemide) block the Na-K-2Cl cotransporter and increase urinary Ca²⁺ excretion.

(Choice D)  Mannitol is an osmotic diuretic.  It is not used as maintenance therapy for any indication as it causes volume depletion and hypernatremia with prolonged use.  It has no effect on Ca²⁺ homeostasis.

(Choice E)  Triamterene and amiloride are potassium-sparing diuretics that inhibit Na⁺ reabsorption in the collecting duct by blocking the epithelial sodium channel.  This decreases net Na⁺/K⁺ exchange, reducing serum K⁺ losses.

Educational objective:
Thiazide diuretics effectively increase renal calcium reabsorption.  In patients with recurrent calcium nephrolithiasis, thiazide diuretics can help prevent stone formation by decreasing urine Ca²⁺ excretion.