trimethoprim and hyperkalaemia

Last edited 06/2018

  • hyperkalaemia has been demonstrated to occur with the administration of both high and standard dosages of trimethoprim

  • trimethoprim reduces renal potassium excretion through the competitive inhibition of epithelial sodium channels in the distal nephron, in a manner identical to the potassium-sparing diuretic amiloride

  • increased risk for hyperkalaemia with trimethoprim treatment appears to be related to both higher dosages and underlying renal impairment
    • probable that other disturbances in potassium homeostasis, such as hyopoaldosteronism and treatment with medications that impair renal potassium excretion, are also risk factors for hyperkalaemia with trimethoprim therapy

  • prevention of this adverse reaction depends upon recognition of patients at risk of developing hyperkalaemia as well as proper dosage selection of trimethoprim for the patient's prevailing glomerular filtration rate

  • management of hyperkalaemia often mandates discontinuation of the drug, volume repletion with isotonic fluids, and other therapies specific to hyperkalaemia
    • in circumstances where continued treatment with trimethoprim is required, induction of high urinary flow rates with intravenous fluids and a loop diuretic, as well as alkalinisation of the urine, have been shown to block the antikaliuretic effect of trimethoprim on distal nephron cells

Hyperkalaemia and non-oliguric renal failure has been associated with trimethoprim use (1,2,3).

Notes:

  • renal failure has been reported with trimethoprim in combination with sulphamethoxazole (cotrimoxazole)
    • trimethoprim can also reversibly increase serum creatinine concentration and reduce creatinine clearance without decreasing glomerular filtration rate both in people with normal renal function and in those with renal allografts
    • trimethoprim alone can cause an important but reversible increase in serum creatinine concentration in acute uncomplicated cystitis and in chronic renal failure
  • a cohort study highlighted the association of prescription of trimethoprim with hyperkalaemia and AKI (acute kidney inury), but not with death, in older adults being treated for a simple UTI (3)
    • the authors have contextulised the results
      • while the odds of hyperkalaemia and AKI with trimethoprim prescription are increased by 127% and 72%, respectively, compared with amoxicillin prescription, the increase in the absolute risk is small
      • the authors state that for 1,000 UTI episodes treated with trimethoprim rather than amoxicillin, there would be one additional case of hyperkalaemia and two of AKI
        • the authors state that "the relative risk increase is similar across population groups, but the higher baseline risk among those taking renin-angiotensin system blockers and potassium-sparing diuretics translates into higher absolute risks of acute kidney injury and hyperkalaemia in these groups...", ie implying that trimethoprim should be used with particular caution in patients taking renin-angiotensin system blockers or potassium-sparing diuretics

Reference:

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trimethoprim