From the Guidelines
Low serum creatinine levels are primarily caused by decreased muscle mass, and the workup should include a comprehensive history and physical examination focusing on muscle mass assessment, nutritional status, and medication review. The most common cause of low creatinine is reduced muscle mass, as creatinine is a byproduct of muscle metabolism 1. Conditions that lead to muscle wasting, such as muscular dystrophy, myasthenia gravis, or advanced age, can result in lower creatinine production. Other causes of low creatinine include:
- Low dietary protein intake
- Reduced creatinine generation with lower muscle mass
- Old age and female sex
- Muscle-wasting conditions
- Amputation
- Malnutrition and critical illness 1
- Pregnancy, which causes hemodilution and increased glomerular filtration rate, both of which lower serum creatinine
- Severe liver disease, which impairs creatine synthesis, the precursor to creatinine
- Certain medications, such as antibiotics like trimethoprim and cimetidine, which inhibit tubular secretion of creatinine
The workup for low creatinine should include:
- Comprehensive history and physical examination
- Laboratory tests, such as:
- Liver function tests
- Complete blood count
- Comprehensive metabolic panel
- Possibly thyroid function tests
- Measuring creatinine clearance through a 24-hour urine collection may be helpful to assess kidney function more accurately 1. While low creatinine itself is not typically treated directly, addressing the underlying cause is essential for proper management.
From the Research
Causes of Low Creatinine Levels
- Severe hepatic disease, such as fulminant hepatitis or advanced primary biliary cirrhosis, can lead to low serum creatinine levels 2
- A low creatinine-to-bodyweight ratio is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD) 3
- Renal dysfunction can affect the urinary creatinine method for estimating skeletal muscle mass in patients with cirrhosis, leading to low creatinine levels 4
- Inhibition of renal transporters involved in active secretion of creatinine can cause reversible elevations in serum creatinine levels, but this may not necessarily be related to low creatinine levels 5
Workup for Low Creatinine Levels
- Assessment of renal function, including glomerular filtration rate (GFR) and creatinine clearance, to determine if low creatinine levels are due to renal dysfunction 2, 6
- Evaluation of liver function, including tests for hepatitis and cirrhosis, to determine if low creatinine levels are due to severe hepatic disease 2, 4
- Measurement of creatinine-to-bodyweight ratio to assess the risk of NAFLD 3
- Consideration of other factors that can affect creatinine levels, such as diet, disease state, and inhibition of renal transporters 5, 6