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Trimethoprim Hyperkalaemia PJP — SCE Infectious Diseases MCQ

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HardHIV MedicineTrimethoprim Hyperkalaemia PJPSCE Infectious Diseases

A 50-year-old man with HIV develops Pneumocystis jirovecii pneumonia. Co-trimoxazole is started at treatment dose (120 mg/kg/day). On day 5, his serum potassium rises to 6.2 mmol/L. He has normal renal function. What is the mechanism?

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Reveal the answer and explanation

Correct answer: C — Trimethoprim blocks the epithelial sodium channel (ENaC) in the distal renal tubule — functionally mimicking Amiloride, causing potassium retention and hyperkalaemia

Trimethoprim blocks the ENaC sodium channel in the renal collecting duct (identical mechanism to Amiloride/Triamterene — potassium-sparing diuretics). At the HIGH doses used for PJP treatment (120 mg/kg/day = much higher Trimethoprim levels than UTI dosing), clinically significant hyperkalaemia occurs in up to 50% of patients. Risk factors: high-dose Co-trimoxazole, renal impairment, concurrent ACEi/ARBs/spironolactone, and elderly patients. Daily potassium monitoring is essential during PJP treatment. Dose reduction or alternative agents may be needed.

Reference: BNF 2024 – Co-trimoxazole; BHIVA 2022 – OI guidelines; NEJM 1993 – Trimethoprim ENaC