Metformin-Associated Acute Kidney Injury and Lactic Acidosis

David Arroyo,Marian Goicoechea,Soledad García Vinuesa,Alberto Tejedor,José Luño,Nayara Panizo,Rosa Melero,Patrocinio Rodríguez-Benítez,Eduardo Verde

doi:10.4061/2011/749653

David Arroyo, Marian Goicoechea + Show 7 more

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https://doi.org/10.4061/2011/749653

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Abstract

Objectives. Metformin is the preferred oral antidiabetic agent for type 2 diabetes. Lactic acidosis is described as a rare complication, usually during an acute kidney injury (AKI). Material and Methods. We conducted a prospective observational study of metformin-associated AKI cases during four years. 29 cases were identified. Previous renal function, clinical data, and outcomes were recorded. Results. An episode of acute gastroenteritis precipitated the event in 26 cases. Three developed a septic shock. Three patients died, the only related factor being liver dysfunction. More severe metabolic acidosis hyperkalemia and anemia were associated with higher probabilities of RRT requirement. We could not find any relationship between previous renal dysfunction and the outcome of the AKI. Conclusions. AKI associated to an episode of volume depletion due to gastrointestinal losses is a serious complication in type 2 diabetic patients on metformin. Previous renal dysfunction (mild-to-moderate CKD) has no influence on the severity or outcome.

Highlights

Metformin is the only biguanide extensively used these days, and has become the first-line oral drug in type 2 diabetes [1]
acute kidney injury (AKI) associated to an episode of volume depletion due to gastrointestinal losses is a serious complication in type 2 diabetic patients on metformin
The reason for including chronic kidney disease (CKD) probably arises from the fact that most cases of lactic acidosis were described in association with an AKI episode derived from hypovolemia secondary to gastrointestinal losses

Summary

Introduction

Metformin is the only biguanide extensively used these days, and has become the first-line oral drug in type 2 diabetes [1]. Metformin-associated lactic acidosis has not been thoroughly characterized. Most cases have been reported associated with an episode of acute kidney injury (AKI), predominantly in intensive care units [2,3,4]. The reason for including chronic kidney disease (CKD) probably arises from the fact that most cases of lactic acidosis were described in association with an AKI episode derived from hypovolemia secondary to gastrointestinal losses. Experimental studies and several series of cases show that adverse outcomes seem more related to hepatic dysfunction than to renal impairment [2, 3, 7]. The pharmacological effect of metformin, as well as the onset of lactic acidosis, could be mediated in part through a self-limiting inhibition of the respiratory chain that restrains hepatic gluconeogenesis while increasing glucose utilization in peripheral tissues [8, 9]

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