title: Treatment of Metformin Intoxication Complicated by Lactic Acidosis and Acute Kidney Injury: The Role of Prolonged Intermittent Hemodialysis.
abstract: Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate and/or its clearance is reduced. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. Confirmation requires measurement of serum metformin by high-performance liquid chromatography-tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment. Thus, based on strong clinical suspicion, renal replacement therapy must be started promptly to achieve efficient drug clearance and correct the metabolic acidosis. However, because metformin accumulates in the intracellular compartment with prolonged treatment, a rebound in serum concentrations due to redistribution is expected at the end of dialysis. We report a case of metformin intoxication, severe lactic acidosis, and acute kidney injury in a diabetic patient with pre-existing chronic kidney disease stage 3, treated effectively with sustained low-efficiency dialysis. We discuss the pathophysiology, differential diagnosis, and treatment options and highlight specific pharmacokinetic issues that should be considered in selecting the appropriate modality of renal replacement therapy.
authors.affiliation: Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy. Electronic address: giuregolisti@gmail.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Regolisti
authors.affiliation: Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Antoniotti
authors.affiliation: Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Fani
authors.affiliation: Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Greco
authors.affiliation: Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Fiaccadori
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000628:therapy*; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000628:therapy*; D000368:Aged; D006801:Humans; D007004:Hypoglycemic Agents / Q000506:poisoning*; D008297:Male; D008687:Metformin / Q000506:poisoning*; D006435:Renal Dialysis / Q000379:methods*; D013997:Time Factors
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Acute intoxication; acute kidney injury (AKI); chronic kidney disease (CKD); diabetes; drug clearance; drug safety; kidney function; lactic acidosis; metformin intoxication; metformin-associated lactic acidosis (MALA); renal replacement therapy (RRT); sustained low-efficiency dialysis (SLED)