How does creatine supplementation affect Glomerular Filtration Rate (GFR) in patients?

Understanding the Difference Between Creatine and GFR in Kidney Function

Creatine supplementation does not adversely affect glomerular filtration rate (GFR) in individuals with normal kidney function, but it can interfere with creatinine-based GFR estimates by increasing serum creatinine without actually changing true kidney function. 1

What is Creatine?

Creatine is a naturally occurring compound that:

• Is stored primarily in skeletal muscle
• Serves as an energy source for muscle contraction
• Is commonly used as a dietary supplement by athletes and bodybuilders to enhance muscle strength and performance
• Is converted to creatinine, which is excreted by the kidneys

What is GFR?

Glomerular Filtration Rate (GFR) is:

• The primary measure of kidney function
• Represents the volume of fluid filtered by the kidneys per unit time
• Is typically estimated using serum creatinine (eGFRcr) in clinical practice
• Can also be measured directly using exogenous filtration markers (mGFR)

How Creatine Affects GFR Assessment

Effect on True Kidney Function

• Multiple studies show that creatine supplementation does not impair actual kidney function in healthy individuals 2, 3, 4
• A randomized controlled trial showed that high-dose creatine supplementation over 3 months actually resulted in decreased cystatin C levels, suggesting improved GFR 5

Effect on Creatinine-Based GFR Estimates

• Creatine supplementation can increase serum creatinine levels without affecting true GFR 6
• In a study of a young man with a single kidney, creatine supplementation increased serum creatinine from 1.03 mg/dL to 1.27 mg/dL while measured GFR using 51Cr-EDTA clearance remained unchanged (81.6 vs 82.0 mL/min/1.73 m²) 6
• This creates a false impression of decreased kidney function when using creatinine-based estimates

Clinical Implications

When Evaluating GFR in Creatine Users

1. Be aware of non-GFR determinants of serum creatinine

   • The KDIGO 2024 guidelines specifically list "high-protein diets and creatine supplements" as factors that affect non-GFR determinants of serum creatinine 1

2. Consider alternative GFR assessment methods

   • Use cystatin C-based estimates (eGFRcys) when creatine supplementation is the only factor affecting creatinine 1
   • Consider combined creatinine and cystatin C-based estimates (eGFRcr-cys) if other comorbidities are present 1
   • For more accurate assessment, measured GFR using exogenous filtration markers may be necessary 1

3. Interpret changes in serum creatinine carefully

   • An increase in serum creatinine in someone taking creatine supplements may not reflect actual kidney function decline
   • KDIGO guidelines recommend assessing the potential for error in eGFR when evaluating changes over time 1

Important Considerations and Caveats

• Pre-existing kidney disease: Creatine supplementation is not recommended for individuals with pre-existing kidney disease or risk factors for kidney dysfunction (diabetes, hypertension) 2, 3

• Monitoring: If creatine supplementation is used, consider baseline and follow-up assessment of kidney function using methods not solely dependent on serum creatinine

• Temporary discontinuation: Consider temporarily discontinuing creatine supplementation before kidney function assessment if accurate creatinine-based estimates are needed

• Clinical context: Always interpret laboratory values in the context of the patient's clinical situation, including supplement use

By understanding the relationship between creatine supplementation and GFR assessment, clinicians can avoid misinterpreting laboratory results and make more accurate assessments of kidney function in individuals who use creatine supplements.