title: Metformin associated lactic acidosis (MALA): clinical profiling and management.
abstract: Metformin (MF) accumulation during acute kidney injury is associated with high anion gap lactic acidosis type B (MF-associated lactic acidosis, MALA), a serious medical condition leading to high mortality. Despite dose adjustment for renal failure, diabetic patients with chronic kidney disease (CKD) stage III-IV are at risk for rapid decline in renal function by whatever reason, so that MF toxicity might arise if the drug is not timely withdrawn. Sixteen consecutive patients were admitted to our Hospital's Emergency Department with clinical findings consistent with MALA. Fifteen had prior history of CKD, 60 % of them with GFR between 30 and 60 ml/min. Of these, 5 required mechanical ventilation and cardiovascular support; 3 promptly recovered renal function after rehydration, whereas 10 (62 %) required continuous veno-venous renal replacement treatment. SOFA and SAPS II scores were significantly related to the degree of lactic acidosis. In addition, lactate levels were relevant to therapeutic choices, since they were higher in dialyzed patients than in those on conservative treatment (11.92 mmol/l vs 5.7 mmol/l, p = 0.03). The overall death rate has been 31 %, with poorer prognosis for worse acidemia, as serum pH was significantly lower in non-survivors (pH 6.96 vs 7.16, p > 0.04). Our own data and a review of the literature suggest that aged, hemodynamically frail patients, with several comorbidities and CKD, are at greater risk of MALA, despite MF dosage adjustment. Moreover, renal replacement therapy rather than simple acidosis correction by administration of alkali seems the treatment of choice, based on eventual renal recovery and overall outcome.
authors.affiliation: Department of Clinical and Molecular Medicine, University of Rome "La Sapienza", Rome, Italy.|Chair and Division of Nephrology, Sant'Andrea University Hospital, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Moioli
authors.affiliation: Department of Clinical and Molecular Medicine, University of Rome "La Sapienza", Rome, Italy.|Chair and Division of Nephrology, Sant'Andrea University Hospital, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Maresca
authors.affiliation: Department of Clinical and Molecular Medicine, University of Rome "La Sapienza", Rome, Italy.|Chair and Division of Nephrology, Sant'Andrea University Hospital, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Manzione
authors.affiliation: Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Antonello Maria
authors.initials: AM
authors.lastname: Napoletano
authors.affiliation: Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Coclite
authors.affiliation: Department of Clinical and Molecular Medicine, University of Rome "La Sapienza", Rome, Italy.|Chair and Division of Nephrology, Sant'Andrea University Hospital, Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pirozzi
authors.affiliation: Department of Clinical and Molecular Medicine, University of Rome "La Sapienza", Rome, Italy.|Chair and Division of Nephrology, Sant'Andrea University Hospital, Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Punzo
authors.affiliation: Department of Clinical and Molecular Medicine, University of Rome "La Sapienza", Rome, Italy. paolo.mene@uniroma1.it.|Chair and Division of Nephrology, Sant'Andrea University Hospital, Rome, Italy. paolo.mene@uniroma1.it.|UOC Nefrologia, A.O. Sant'Andrea, Via di Grottarossa 1035-1039, 00189, Rome, Italy. paolo.mene@uniroma1.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Menè
mesh_terms: D000136:Acid-Base Equilibrium; D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000401:mortality; D003928:Diabetic Nephropathies / Q000209:etiology / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008499:Medical Records; D008687:Metformin / Q000009:adverse effects*; D008875:Middle Aged; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D012189:Retrospective Studies; D012307:Risk Factors; D012384:Rome; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Acute renal failure; Bicarbonate; Hemodialysis; Lactic acidosis; Metformin; Type 2 diabetes