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Trimethoprim ENaC Block Hyperkalaemia CKD — ESENeph MCQ

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ModerateElectrolyte DisordersTrimethoprim ENaC Block Hyperkalaemia CKDESENeph

A 55-year-old man with CKD G4 on Ramipril has a serum potassium of 5.3 mmol/L. His GP prescribes Co-trimoxazole for a UTI. Three days later, potassium rises to 6.4 mmol/L. What is the mechanism?

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Correct answer: B — Trimethoprim (in Co-trimoxazole) blocks the epithelial sodium channel (ENaC) in the collecting duct – acting like Amiloride – reducing potassium secretion; combined with RASi and CKD, this causes dangerous hyperkalaemia

Trimethoprim blocks ENaC in the distal nephron (same mechanism as Amiloride/potassium-sparing diuretics), impairing potassium secretion. At standard doses, this effect is usually modest in patients with normal renal function. However, in CKD patients already on RASi (which suppresses aldosterone – the primary driver of ENaC-mediated K secretion), the addition of Trimethoprim can cause life-threatening hyperkalaemia. BNF and NICE recommend checking potassium within 3-5 days of starting Co-trimoxazole in CKD patients on RASi. Alternative antibiotics should be considered when possible.

Reference: BNF 2024; Antoniou et al 2010 – Trimethoprim Hyperkalaemia; NICE