From the Guidelines
Lactic acidosis is primarily caused by metformin use, especially in patients with renal insufficiency, as well as by certain antiretroviral agents, such as NRTIs, particularly in combination with other risk factors like obesity and prolonged use.
Causes of Lactic Acidosis
- Metformin use: Metformin can cause lactic acidosis, especially in patients with renal insufficiency, as it is cleared by the kidneys and can accumulate to toxic levels 1.
- Antiretroviral agents: Certain antiretroviral agents, such as NRTIs, can cause lactic acidosis, particularly in combination with other risk factors like obesity and prolonged use 1.
- Renal insufficiency: Renal insufficiency can increase the risk of lactic acidosis, especially in patients taking metformin or other medications that are cleared by the kidneys 1.
- Dehydration: Dehydration can also contribute to the development of lactic acidosis, especially in patients taking metformin or other medications that can cause lactic acidosis 1.
- Other risk factors: Other risk factors for lactic acidosis include cardiac disease, hypoperfusion, old age, and chronic pulmonary disease 1. Some medications, such as thiazolidinediones, do not typically cause lactic acidosis, but can increase the risk of fluid retention and other side effects 1. NRTIs, such as stavudine and didanosine, can cause lactic acidosis, particularly in combination with other antiretroviral agents 1. DPP-4 inhibitors and GLP-1 receptor agonists are not typically associated with an increased risk of lactic acidosis 1.
From the Research
Causes of Lactic Acidosis
The causes of lactic acidosis can be divided into two main categories:
- Type A lactic acidosis, which occurs when the body must regenerate ATP without oxygen (tissue hypoxia) due to circulatory, pulmonary, or hemoglobin transfer disorders 2
- Type B lactic acidosis, which occurs in disorders where tissue oxygenation is maintained, such as liver disease, inhibition of gluconeogenesis, pyruvate dehydrogenase (thiamine) deficiency, and uncoupling of oxidative phosphorylation 2
Specific Causes
Some specific causes of lactic acidosis include:
- Metformin-associated lactic acidosis (MALA), which is typically necessary to cause 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) 3
- Cyanide poisoning or certain malignancies, which can cause overproduction of lactate 2
- Phenformin therapy, hereditary enzymatic defects, hematological malignancy, prolonged fasting, shock with or without septicemia, and occasionally without any underlying disease ("idiopathic" lactic acidosis) 4
- Impaired tissue oxygenation, such as in septic shock 5
Underlying Mechanisms
The underlying mechanisms of lactic acidosis involve an imbalance between production and clearance of lactate, with the liver playing a major role in removing lactate and hydrogen ions 6, 4