Can creatine supplementation decrease estimated Glomerular Filtration Rate (eGFR)?

Creatine Supplementation and eGFR: Effects on Kidney Function

Creatine supplementation does not decrease actual glomerular filtration rate (GFR), but it can artificially lower estimated GFR (eGFR) values due to increased serum creatinine levels without affecting true kidney function in individuals with normal renal function.

Mechanism of Effect on eGFR

Creatine supplementation affects kidney function measurements in the following ways:

• Artificial elevation of serum creatinine: Creatine is metabolized to creatinine, leading to increased serum creatinine levels that do not reflect actual kidney dysfunction 1
• False decrease in eGFR calculations: Since eGFR formulas use serum creatinine as a key variable, the elevated creatinine artificially lowers calculated eGFR values 1, 2
• No change in actual GFR: When measured by gold standard methods (like 51Cr-EDTA clearance), true GFR remains unchanged despite creatine supplementation 3

Evidence from Clinical Studies

Research consistently shows that creatine supplementation affects laboratory values but not actual kidney function:

• In a controlled single-patient study of a 20-year-old man with a single kidney who received 20g/day of creatine monohydrate, serum creatinine increased from 1.03 mg/dL to 1.27 mg/dL, but 51Cr-EDTA clearance (true GFR) remained unchanged (81.6 vs 82.0 mL/min/1.73m²) 1, 3

• Long-term studies (10 months to 5 years) of creatine supplementation in healthy athletes showed no detrimental effects on actual kidney function parameters including glomerular filtration rate, tubular reabsorption, and glomerular membrane permeability 4

Clinical Implications

For Healthy Individuals

• Creatine supplementation (5-30g/day) has not been shown to cause actual kidney dysfunction in healthy individuals with normal kidney function 5, 6
• The apparent decrease in eGFR is due to laboratory artifact rather than actual kidney injury

For At-Risk Individuals

• Caution is advised for individuals with:
  • Pre-existing kidney disease
  • Risk factors for kidney dysfunction (diabetes, hypertension)
  • Reduced baseline GFR 6

Recommendations for Clinical Practice

1. Understand the laboratory artifact: Recognize that increased serum creatinine and decreased eGFR in creatine users likely represents a laboratory artifact rather than actual kidney dysfunction

2. Consider alternative GFR measurements: When assessing kidney function in creatine users:

   • Use cystatin C-based eGFR formulas (not affected by creatine)
   • Consider direct GFR measurement methods when necessary
   • Use 24-hour urinary creatinine clearance as an alternative 2

3. Patient education: Inform patients that:

   • Routine laboratory tests may show falsely elevated creatinine and decreased eGFR
   • These changes do not necessarily indicate kidney damage
   • Consider temporary discontinuation of creatine before kidney function testing if accurate assessment is needed

Common Pitfalls to Avoid

• Misdiagnosis of CKD: Avoid diagnosing chronic kidney disease based solely on eGFR in creatine users without considering the supplement's effect on laboratory values 2

• Unnecessary interventions: Prevent unnecessary diagnostic workups or treatment changes based on falsely decreased eGFR values

• Failure to consider other causes: Always evaluate for true kidney dysfunction if other signs of kidney disease are present (proteinuria, hematuria, hypertension)

In conclusion, while creatine supplementation can artificially lower eGFR values due to increased serum creatinine levels, current evidence indicates it does not cause actual kidney dysfunction in individuals with normal renal function.