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.
Similar content being viewed by others
References
Kane, SP. Clincalc.com [Internet]. ClinCalc LLC; 2020 [updated 2016 May 09; cited 2020 Jun 11]. Available from: https://clincalc.com/DrugStats/
Callelo DP, et al. Extracorporeal treatment for metformin poisoning: systematic review and recommendations from the extracorporeal treatments in poisoning workgroup. Crit Care Med. 2015;43(8):1716–30. https://doi.org/10.1097/CCM.0000000000001002.
Regolisti G, Antoniotti R, Fani F, Greco P, Fiaccadori E. Treatment of metformin intoxication complicated by lactic acidosis and acute kidney injury: the role of prolonged intermittent hemodialysis. Am J Kidney Dis. 2017 Aug;70(2):290–6. https://doi.org/10.1053/j.ajkd.2016.12.010.
Glucophage [Packet Insert]. Bristol-Myers Squibb Company, NJ; 2018.
Hernandez SH, Howland M, Schiano TD, Hoffman RS. The pharmacokinetics and extracorporeal removal of N-acetylcysteine during renal replacement therapies. Clin Toxicol (Phila). 2015;53(10):941–9. https://doi.org/10.3109/15563650.2015.1100305.
Ayoub P, Hétu PO, Cormier M, Benoit A, Palumbo A, Dubé MC, Gosselin S,Ghannoum M. Toxicokinetics of Metformin During Hemodialysis. Kidney Int Rep. 2017;2(4):759–762. doi: https://doi.org/10.1016/j.ekir.2017.02.017. eCollection 2017 Jul.
Suzuki K, Okada H, Yoshida S, Okamoto H, Suzuki A, Suzuki K, et al. Effect of high-flow high-volume-intermittent hemodiafiltration on metformin-associated lactic acidosis with circulatory failure: a case report. J Med Case Rep. 2018;12:280.
Smith FC, Kumar SS, Furlong TJ, Gangaram SV, Greenfield JR, Stocker SL, et al. Pharmacokinetics of metformin in patients receiving regular hemodiafiltration. American journal of kidney diseases: the official journal of the National Kidney Foundation. 2016;68:990–2.
Kajbaf F, Bennis Y, Hurtel-Lemaire AS, Andrejak M, Lalau JD. Unexpectedly long half-life of metformin elimination in cases of metformin accumulation. Diabetic Medicine. 2016;33:105–10.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Consent for publication of this case was obtained from the patient in accordance with JMT. policy.
Conflict of Interest
The authors report no conflicts of interest.
Additional information
Supervising Editor: Mark B. Mycyk, MD
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 1303 kb)
Rights and permissions
About this article
Cite this article
Harding, S.A., Biary, R., Hoffman, R.S. et al. A Pharmacokinetic Analysis of Hemodialysis for Metformin-Associated Lactic Acidosis. J. Med. Toxicol. 17, 70–74 (2021). https://doi.org/10.1007/s13181-020-00802-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13181-020-00802-7