Does elevated creatinine (kidney function test) cause lactic acidosis?

From the Guidelines

Elevated creatinine does not directly cause lactic acidosis, but it can contribute to or worsen existing lactic acidosis by impairing the kidneys' ability to clear lactate from the bloodstream. Elevated creatinine is a marker of decreased kidney function, which can lead to a buildup of toxins, including lactate, in the body. However, lactic acidosis is typically caused by conditions that lead to tissue hypoxia, such as shock, severe heart failure, or sepsis, or by medications like metformin, particularly when they accumulate due to reduced kidney function 1.

The relationship between elevated creatinine and lactic acidosis is complex, and understanding this relationship is crucial for managing patients with kidney disease who may be at higher risk for developing lactic acidosis. Metformin, a commonly used medication for diabetes, should be used with caution in patients with impaired kidney function, as it can increase the risk of lactic acidosis 1. The risk of lactic acidosis associated with metformin is higher in patients with severe kidney impairment, and the medication should be avoided or used with caution in patients with a creatinine clearance of less than 30-45 mL/min/1.73m² 1.

Key points to consider:

• Elevated creatinine is a marker of decreased kidney function, not a direct cause of lactic acidosis
• Impaired kidney function can contribute to or worsen existing lactic acidosis by impairing lactate clearance
• Metformin should be used with caution in patients with impaired kidney function due to the increased risk of lactic acidosis
• The risk of lactic acidosis associated with metformin is higher in patients with severe kidney impairment
• Patients with kidney disease should be closely monitored for signs of lactic acidosis, particularly when taking medications like metformin 1.

From the FDA Drug Label

Renal impairment — The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney.

Elevated creatinine, which indicates renal impairment, may increase the risk of lactic acidosis. This is because metformin is substantially excreted by the kidney, and renal impairment can lead to metformin accumulation, increasing the risk of lactic acidosis.

• Key points:
  • Renal impairment increases the risk of metformin-associated lactic acidosis
  • Elevated creatinine is a marker of renal impairment
  • Metformin accumulation can occur in patients with renal impairment, increasing the risk of lactic acidosis 2

From the Research

Elevated Creatinine and Lactic Acidosis

• Elevated creatinine levels are often associated with kidney dysfunction, which can lead to a buildup of waste products in the body, including lactic acid 3, 4, 5, 6, 7.
• Lactic acidosis is a condition characterized by the accumulation of lactic acid in the body, which can be caused by various factors, including kidney disease, diabetes, and certain medications 4, 5, 6, 7.
• Studies have shown that metformin, a medication commonly used to treat type 2 diabetes, can cause lactic acidosis, especially in patients with kidney disease or renal insufficiency 4, 5, 6, 7.
• Elevated creatinine levels can be a contributing factor to the development of lactic acidosis, as impaired kidney function can lead to a decrease in the clearance of lactic acid from the body 5, 7.

Relationship between Creatinine and Lactic Acidosis

• Research has shown that there is a correlation between creatinine levels and lactic acidosis, with higher creatinine levels being associated with a higher risk of developing lactic acidosis 5.
• A study published in the Clinical Toxicology journal found that metformin plasma concentrations were correlated with creatinine, pH, and lactate levels, suggesting that kidney function plays a role in the development of lactic acidosis 5.
• Another study published in the Medizinische Klinik journal reported a case of metformin-associated lactic acidosis with acute renal failure, highlighting the importance of monitoring kidney function in patients taking metformin 7.

Treatment and Prevention

• Treatment of lactic acidosis typically involves addressing the underlying cause, such as discontinuing metformin therapy and providing supportive care, including hemodialysis or bicarbonate therapy 3, 4, 7.
• Prevention of lactic acidosis involves closely monitoring kidney function in patients taking metformin and adjusting the dose or discontinuing therapy if kidney function deteriorates 5, 7.