A Pharmacokinetic Analysis of Hemodialysis for Metformin-Associated Lactic Acidosis

Authors

Stephen A Harding
Rana Biary
Robert S Hoffman
Mark K Su
Mary Ann Howland

Publication Date

1-1-2021

Journal

Journal of Medical Toxicology

DOI

10.1007/s13181-020-00802-7

PMID

32789583

PMCID

PMC7785761

PubMedCentral® Posted Date

8-20-2020

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Acidosis, Lactic, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Male, Metabolic Clearance Rate, Metformin, Middle Aged, Renal Dialysis, Renal Elimination, Treatment Outcome, Metformin, Biguanides, Lactic acidosis, Hemodialysis, Drug clearance

Abstract

OBJECTIVE: Although hemodialysis is recommended for patients with severe metformin-associated lactic acidosis (MALA), the amount of metformin removed by hemodialysis is poorly documented. We analyzed endogenous clearance and hemodialysis clearance in a patient with MALA.

METHODS: A 62-year-old man with a history of type II diabetes mellitus presented after several days of vomiting and diarrhea and was found to have acute kidney injury (AKI) and severe acidemia. Initial serum metformin concentration was 315.34 μmol/L (40.73 μg/mL) (typical therapeutic concentrations 1-2 μg/mL). He underwent 6 h of hemodialysis. We collected hourly whole blood, serum, urine, and dialysate metformin concentrations. Blood, urine, and dialysate samples were analyzed, and clearances were determined using standard pharmacokinetic calculations.

RESULTS: The total amount of metformin removed by 6 h of hemodialysis was 888 mg, approximately equivalent to one therapeutic dose. Approximately 142 mg of metformin was cleared in the urine during this time. His acid-base status and creatinine improved over the following days. No further hemodialysis was required.

CONCLUSION: We report a case of MALA likely secondary to AKI and severe volume depletion. The patient improved with supportive care, sodium bicarbonate, and hemodialysis. Analysis of whole blood, serum, urine, and dialysate concentrations showed limited efficacy of hemodialysis in the removal of metformin from blood, contrary to previously published data. Despite evidence of acute kidney injury, a relatively large amount of metformin was eliminated in the urine while the patient was undergoing hemodialysis. These data suggest that clinical improvement is likely due to factors besides removal of metformin.

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