A patient with nephrogenic diabetes insipidus is started on hydrochlorothiazide. Paradoxically, his urine output decreases and urine osmolality increases. The mechanism underlying this paradoxical antidiuretic effect of thiazides is:
- A Reduced glomerular filtration rate and enhanced proximal tubular sodium and water reabsorption ✓
- B Enhanced water permeability in the collecting duct via aquaporin-2 upregulation
- C Increased ADH secretion from the posterior pituitary
- D Direct stimulation of V2 receptors in the collecting duct
Correct answer: A. Reduced glomerular filtration rate and enhanced proximal tubular sodium and water reabsorption
Explanation
Thiazides induce mild volume depletion, which activates the renin-angiotensin-aldosterone system and enhances proximal tubular reabsorption of sodium and water. This reduces delivery of filtrate to the diluting segments and decreases free water excretion. The net effect is concentrated urine despite the diuretic. Option C is wrong because thiazides do not stimulate ADH release. Option B describes the mechanism of vasopressin, not thiazides.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th ed.
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