A 35-year-old man with a history of recurrent calcium oxalate kidney stones is found to have hypercalciuria with serum calcium of 10.8 mg/dL (upper normal). His PTH is low-normal and 1,25-(OH)₂ vitamin D is elevated. A thiazide diuretic is prescribed. Through which mechanism do thiazides reduce urinary calcium in this patient?
- A Inhibition of the Na-Cl cotransporter in the distal convoluted tubule, causing enhanced paracellular calcium reabsorption
- B Inhibition of the Na-Cl cotransporter in the distal convoluted tubule, causing enhanced active calcium reabsorption via TRPV5 ✓
- C Inhibition of NKCC2 in the thick ascending limb, reducing the lumen-positive voltage
- D Stimulation of the calcium-sensing receptor in the thick ascending limb
Correct answer: B. Inhibition of the Na-Cl cotransporter in the distal convoluted tubule, causing enhanced active calcium reabsorption via TRPV5
Explanation
Thiazides inhibit NCC in the distal convoluted tubule, causing natriuresis. The reduced intracellular sodium enhances basolateral Na⁺/Ca²⁺ exchanger (NCX) activity, which increases active transcellular calcium reabsorption via TRPV5. This is the basis for thiazide use in hypercalciuria. Distractor A is wrong because DCT calcium reabsorption is transcellular, not paracellular. Distractor C describes loop diuretic action, which increases (not decreases) urinary calcium.
Reference: Brenner and Rector's The Kidney, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.