Correct Answer: D. Decreased Calcium Excretion
Hydrochlorothiazide (HCTZ) is actually a beneficial and rational drug choice for a hypertensive patient with calcium-containing renal stones. The key mechanism is that thiazide diuretics decrease urinary calcium excretion (hypocalciuria), which directly reduces the supersaturation of calcium in the urine and thereby lowers the risk of calcium stone formation.
Mechanism of hypocalciuria with thiazides: Thiazides act on the distal convoluted tubule (DCT) to inhibit the Na⁺/Cl⁻ cotransporter (NCC). This causes mild volume depletion, which stimulates compensatory sodium reabsorption in the proximal tubule. Calcium reabsorption in the proximal tubule is coupled to sodium reabsorption — as more sodium (and water) is reabsorbed proximally, more calcium is also reabsorbed, reducing the amount of calcium delivered to and excreted in the urine. Additionally, thiazides directly enhance calcium reabsorption in the DCT via upregulation of apical TRPV5 channels and basolateral NCX1 exchangers. The net result is decreased urinary calcium, making the urine less lithogenic.
This dual action — antihypertensive effect + reduction in urinary calcium — makes HCTZ an ideal first-line agent in hypertensive patients with recurrent calcium oxalate or calcium phosphate stones. It is a classic "two birds, one stone" pharmacological choice frequently tested in NEET PG.
Why Other Options Are Wrong
- A. Decreased citrate excretion — Thiazides do not primarily decrease urinary citrate. In fact, by causing mild hypokalemia and intracellular acidosis, there can be a modest reduction in citrate, but this is not the defining or therapeutically relevant action. Decreased citrate would worsen stone risk, which is the opposite of the intended benefit here.
- B. Increased calcium excretion — This is the opposite of what thiazides do. Loop diuretics (e.g., furosemide) increase urinary calcium excretion (hypercalciuria) and would worsen stone disease. Thiazides are distinguished from loop diuretics precisely because they decrease calcium excretion.
- C. Increased oxalate absorption — Thiazides have no recognized mechanism of increasing intestinal oxalate absorption. This is a distractor with no pharmacological basis relevant to thiazide action.
Reference: KD Tripathi Pharmacology — Diuretics; Brenner & Rector's The Kidney — Nephrolithiasis