Journal of the American Society of Nephrology
Introduction: Metformin is a small, non-protein-bound molecule that can cause lactic acidosis in 6 out of 100,000 patients with a mortality rate of 30-50%. Concurrent euglycemic diabetic ketoacidosis (DKA) from sodium-glucose co-transporter-2 (SGLT2) inhibitor has been reported in one case. We report a unique case of a patient with acute kidney injury (AKI) in the setting of metformin-induced lactic acidosis and osmotic diuresis due to euglycemic DKA complicated by celecoxib use. Case Description: A 66-year-old female with a past medical history of type 2 diabetes mellitus for 21 years on metformin 1000 mg twice daily and empagliflozin 25 mg daily with baseline eGFR 51 mL/min/1.73m2 5 months prior, who was also on celecoxib 200 mg daily for 40 days presented for elective cervical discectomy which was canceled due to AKI. On exam, blood pressure was 119/59 mmHg, pulse was 92 beats/min, and the temperature was 36.1°C. She was tachypneic at 24 breath/min. Labs showed sodium 136 mg/dL, potassium 8.4 mg/dL, bicarbonate 9 mg/dL, BUN 83 mg/dl, creatinine 8.78 mg/dL, and glucose 117 g/dL. Lactic acid was 13.5 mmol/L, beta-hydroxybutyrate 5.9 mmol/L, serum osmolality 336 mOsmol/kg with no osmolar gap. She underwent conventional hemodialysis (HD) for 3 hours followed by 18 hours of continuous kidney replacement therapy (CKRT). She required an insulin drip with 5% dextrose in normal saline for 24 hours. Lactic acid was 3.8 mmol/L after 24 hours. Creatinine improved to 2.46 mg/dL on day 4 without further intervention. She was discharged home off metformin, empagliflozin, and celecoxib. Discussion: Metformin is readily dialyzable but has a large volume of distribution. There is no specific antidote available to reverse the toxic effects of metformin or consensus on the modality of renal replacement therapy. Previously demonstrated biphasic elimination pattern of metformin intoxication suggests that a brief HD session is not sufficient to eliminate metformin due to a rebound phenomenon, but it is essential to correct severe acidosis and electrolyte derangements. Hyperkalemia required the use of HD which needed to be followed by CKRT as a more physiological way to maximize metformin removal and prevent ongoing lactic acid production. We suggest prudence in the combination of metformin with SGLT2 inhibitor use, specifically in patients exposed to nephrotoxic drugs or procedures.
Sardarli K, Leong R, Gill I, Zarouk SS. A patient with combined metformin-induced lactic acidosis and euglycemic diabetic ketoacidosis. J Am Soc Nephrol. 2021; 32(Suppl 2):384.