A hypertensive patient started on chlorthalidone develops an acute gouty attack six weeks later. The mechanism of thiazide-induced hyperuricemia is:

• A Increased hepatic urate production stimulated by volume depletion
• B Alkaline urine pH converting soluble urate to insoluble monosodium urate
• C Enhanced urate reabsorption mediated by upregulated GLUT9 channels in the collecting duct
• D Competition between the diuretic and uric acid for the organic acid secretory transporters in the proximal tubule ✓

Explanation

Uric acid is secreted in the proximal tubule via organic anion transporters (URAT1 and related OAT carriers), and thiazides compete for the same anion exchange pathways, blocking urate secretion and raising serum levels. Volume contraction adds a smaller component by increasing proximal urate reabsorption, but transporter competition is the dominant mechanism taught in standard texts. Losartan is the antihypertensive that instead promotes urate excretion at these transporters.

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

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