Possible synergistic effect of metformin and enalapril on the development of hyperkaliemic lactic acidosis

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A 71 year old hypertensive, non insulin-dependent diabetic patient with moderate renal insufficiency taking 500 mg/d of metformin and 5 mg/d of enalapril, developed metabolic acidosis characterized by fairly elevated anion gap, hyperchloremia, severe hyperkaliemia, normal plasma level of 3-hydroxybutyric acid, absence of ketonuria and high plasma level of lactic acid. This biochemical feature allowed us to ascribe the pathogenesis of metabolic acidosis, both to the increased plasma level of lactic acid and to the type IV renal tubular acidosis syndrome, the precipitating factor being an infection of urinary tract (as we assumed on the basis of the urine culture). The patient was dehydrated and lethargic; the ECG revealed the presence of nonparoxysmal junctional tachycardia. The clinical evolution was favorable under the treatment with an infusion of isotonic saline solutions, mild alkalinizing solutions, low-dose regular insulin and antibiotics. It is likely that metformin and enalapril, regularly taken by this nephropathic patient, could have played an iatrogenic role, even if the doses were low. This case highlights the importance of complying with the contraindications of these drugs, to avoid the rare but reported life-threatening complications of metformin administration.