A 55-year-old man with chronic gout and diabetic nephropathy has an eGFR of 22 mL/min. His physician considers probenecid for urate lowering but rejects it. The reason probenecid is unsuitable in this patient is that:

• A It precipitates acute gout flares regardless of glomerular function
• B It is nephrotoxic through crystallisation in the collecting ducts
• C It raises serum urate further in renal failure through volume contraction
• D Uricosuric action depends on active tubular secretion of the drug into the proximal tubule, which fails once eGFR falls below about 30 mL/min ✓

Explanation

Probenecid must itself be secreted by the organic anion transporters of the proximal tubule to reach luminal URAT1 and OAT4, whose inhibition produces uricosuria. When eGFR falls below roughly 30 mL/min, insufficient drug reaches the tubular lumen and the uricosuric effect is lost. It is also avoided in patients with a history of urate nephrolithiasis because it increases urinary urate concentration. Its flare-precipitating tendency is managed with prophylaxis, not an absolute bar.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.