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risk for rapid decline in renal function by whatever reason, so that MF toxicity might arise if the drug is not timely withdrawn.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.

Activation of the Anaphase Promoting Complex reverses multiple drug resistant cancer

“…Generally, there was a decrease in food interest and this was interpreted to indicate possible gastrointestinal intolerance of metformin [38]. Laboratory investigations spanning metformin monotherapy in these subjects did not show a metabolic acidosis (data not shown), a relevant consideration given that lactic acidosis has been reported as a rare complication of metformin use in humans with renal failure [39,40]. There was no alteration to differential cell counts, with immature bands being equally present before and after weeks of treatment.…”

Lactic acidosis and the relationship with metformin usage

“…[23,24] However, a more careful approach is to be considered in patients who are at risk of abrupt worsening of renal function, especially in patients with CKD stage 3 to 4, who may have serious clinical conditions predisposing to AKI. [25] …”

Emergency medicine point of view on epidemiology of diabetes and diabetes-related complications

“…Inhibition of mitochondrial chain and decrease in cellular production of ATP reduces the level of hepatic gluconeogenesis and causes increased concentration of lactic acid, which is a specific substrate of retained gluconeogenesis. Increased lactic acid levels may also increase the transition from aerobic to anaerobic metabolism [40]. Lactic acid accumulated in the serum in this way is a consequence of the occurrence of acidosis.…”