Metformin-related lactic acidosis in patients with acute kidney injury

Devetzis, Vassilios; Passadakis, Ploumis; Panagoutsos, Stelios; Theodoridis, Marios; Thodis, Elias; Georgoulidou, Anastasia; Vargemezis, Vassilis

doi:10.1007/s11255-010-9845-1

Cited by 17 publications

(10 citation statements)

References 50 publications

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“…However, MALA can occur in patients with even mild renal dysfunction [30] and patient outcome seems to be correlated with severity of the underlying disease, highlighting the need for judicious use of metformin even in otherwise lower-risk patients. MALA is more likely to occur in patients who acutely develop renal impairment from dehydration, vomiting or diarrhea, surgery, etc., especially in elderly subjects who have a reduced glomerular filtration rate [31][32][33][34][35][36][37][38]. Dehydration can cause acute renal failure and reduce metformin clearance, resulting in increased plasma metformin levels, especially if metformin administration is continued [27].…”

Section: Risk Factors For Malamentioning

confidence: 99%

Metformin-associated lactic acidosis: Current perspectives on causes and risk

DeFronzo

Fleming²,

Chen³

et al. 2016

Metabolism

458

333

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Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (<10 cases per 100,000 patient-years). Several groups have suggested that current renal function cutoffs for metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the results of future studies. This literature-based review provides an update on the impact of renal function and other conditions on metformin plasma levels and the risk of MALA in patients with type 2 diabetes.

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Section: Risk Factors For Malamentioning

confidence: 99%

Metformin-associated lactic acidosis: Current perspectives on causes and risk

DeFronzo

Fleming²,

Chen³

et al. 2016

Metabolism

458

333

View full text Add to dashboard Cite

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“…Although data are anecdotal and reporting bias cannot be excluded, most of the patients treated with ECTR (especially intermittent hemodialysis) improved after initiation and had a favorable outcome, including patients who ingested more than 2 g/kg, had a pH less than 6.7, had a lactate concentration over 30 mmol/L, or a metformin concentration over 100 mg/L (28, 29, 34-37, 66, 73, 88, 91, 98, 104, 111, 116-119, 130, 138, 139, 145, 160, 161, 163, 172, 174, 181, 183, 185, 188, 198, 204, 208, 209, 218-220). Occasionally, this reported improvement was dramatic, soon after the initiation of ECTR (34, 86,96,98,144,[166][167][168]191). Conversely, there were also cases where little to no improvement was noted during ECTR (13, 14, 76, 84, 107, 155,162,184,198), which may reflect a delay in ECTR initiation (e.g., tardiness in ensuring central vascular access or unnecessarily prolonged bicarbonate therapy) (13,14,162,198), a treatment shortened prematurely (e.g., metabolic derangements not fully corrected) (107), and/or the use of a less efficient ECTR on the basis of hemodynamic instability (13,76,198).…”

Section: Recommendationsmentioning

confidence: 99%

Extracorporeal Treatment for Metformin Poisoning

Calello¹,

Liu

Wiegand

et al. 2015

Critical Care Medicine

175

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“…Although the AMH and guidelines in Australia do not have the same recommendation as the PI, that metformin should be avoided in CrCl less than 60 mL/min, dosage reduction according to renal function is recommended. LA may be more likely in patients with AKF, rather than chronic kidney disease . Patients with a diagnosis of AKF were not included in this study.…”

Section: Discussionmentioning

confidence: 99%