A 35-year-old man with recurrent calcium oxalate kidney stones is started on thiazide prophylaxis. The mechanism by which thiazides reduce urinary calcium excretion is:

• A Direct inhibition of the calcium sensing receptor in the collecting duct
• B Inhibition of paracellular calcium flux in the thick ascending limb
• C Increased filtration fraction raising peritubular calcium concentration
• D Enhanced distal tubular calcium reabsorption secondary to mild volume contraction ✓

Explanation

Thiazides inhibit the NCC symporter in the distal convoluted tubule, causing mild volume contraction. This triggers compensatory proximal sodium reabsorption, which passively drags calcium along, and enhances active transcellular calcium uptake in the distal tubule through apical TRPV5 channels upregulated by low-volume states. Net effect is reduced urinary calcium, hence their value in recurrent stone formers.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th ed.

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