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Why does metformin kill dialysis patients?
Just want to know why 96 percent of dialysis patients who take metformin by accident die with in 72 hours
2 Answers
- 1 decade agoFavorite Answer
Whilst I cannot vouch for the statistic that you have given above, I can postulate a mechanism for you.
Metformin is a weakly acidic drug that is eliminated almost exclusively through the renal tract. Hence patients who have no remaining renal function and are anuric (the majority of dialysis patients will be in this state) will be unable to secrete H+ ions in the proximal tubule (the usual method for excreting acid from the blood), and will become acidaemic. This will be seen on blood gas as an increased anion gap metabolic acidosis (the metformin itself is the acidic unmeasured anion).
Dialysis patients who still urinate may still be able to acidify their urine, depending on remaining tubular function, and so will possibly avoid the fate detailed below.
If the patient dialyses after this event they will have their pH corrected at this point, if they do not then they will remain acidotic. Acidosis has profoundly negative effects on enzyme function in the body, but largely speaking causes death by righward shifting of the Oxygen dissociation curve. This makes it harder for the blood to bind and release oxygen, reducing tissue oxygenation. There are also knock on effects on CO2 carriage (the Haldane effect), and also the compound effect of this tissue hypoxia causing an increase in lactate (another weak acid) and an increase in acidosis.
I hope that succinctly explains the issues for you.