A 58-year-old man with primary hypertension and a history of calcium oxalate nephrolithiasis is started on antihypertensive therapy. The structure marked **C** in the diagram is the site of action of his chosen drug. Which of the following best describes the mechanism and clinical consequence of the drug acting on this segment?

Question

Accepted Answer

A. Inhibits Na+/Cl− co-transporter; decreases urinary calcium excretion and increases serum calcium. The structure marked **C** is the distal convoluted tubule (DCT). Thiazide diuretics (hydrochlorothiazide, chlorthalidone, indapamide) are first-line agents for primary hypertension per JNC-8 and Indian HTN guidelines. They act by inhibiting the Na+/Cl− co-transporter (NCC) in the DCT. Critically, thiazides DECREASE urinary calcium excretion (opposite of loop diuretics), leading to hypercalcemia. This property makes thiazides beneficial in patients with calcium oxalate stones and osteoporosis—the clinical anchor for this question. The mechanism involves reduced calcium reabsorption in the proximal tubule secondary to mild volume depletion and increased distal calcium reabsorption via the Na+/Ca2+ exchanger. Common side effects include hypokalemia, hyponatremia, hyperglycemia, hyperuricemia, and hyperlipidemia (Guyton & Hall 14e Ch 32; KD Tripathi 9e Ch 41).

Answer

B. Inhibits Na+/K+/2Cl− co-transporter; increases urinary calcium excretion and decreases serum calcium

Answer

C. Blocks aquaporin-2 channels; causes nephrogenic diabetes insipidus and polyuria

Answer

D. Inhibits H+/K+ ATPase; causes metabolic acidosis and hyperkalemia

Explanation

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