Long-term hydrochlorothiazide therapy lowers urinary calcium excretion. The mechanism responsible for this hypocalciuric effect is:

• A Increased calcium reabsorption in the thick ascending limb via activation of NKCC2
• B Distal tubular volume contraction leading to passive paracellular calcium reabsorption in the proximal tubule ✓
• C Direct stimulation of the calcium sensing receptor in the collecting duct
• D Inhibition of sodium chloride reabsorption at the distal convoluted tubule with upregulation of apical calcium channels

Explanation

Thiazides block NCC in the distal convoluted tubule, causing mild volume contraction. This enhances proximal tubular sodium and water reabsorption, which passively drags calcium along paracellularly, reducing urinary calcium. The resulting hypocalciuria explains both the reduced recurrence of calcium oxalate stones and the modest bone mineral benefit in hypertensive postmenopausal women. Option D describes enhanced distal calcium handling but the accepted textbook mechanism is proximal enhancement secondary to volume depletion.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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