Can creatinine (Creatinine) supplementation cause a decrease in calculated Glomerular Filtration Rate (GFR)?

Effect of Creatine Supplementation on Calculated GFR

Yes, creatine supplementation can cause a decrease in calculated GFR without affecting actual kidney function, as it artificially elevates serum creatinine levels. 1, 2

Mechanism and Impact

Creatine supplementation affects estimated GFR (eGFR) through the following mechanisms:

• Direct effect on serum creatinine: Creatine is a precursor to creatinine, and supplementation increases the serum creatinine pool without affecting actual kidney function 2, 3
• False appearance of kidney dysfunction: The elevated serum creatinine leads to a falsely decreased eGFR when using creatinine-based estimation formulas like MDRD or CKD-EPI 1, 3
• Magnitude of effect: Studies show that creatine supplementation can increase serum creatinine by approximately 0.2-0.3 mg/dL, which can significantly impact calculated GFR 4

Evidence from Clinical Studies

Research demonstrates that this effect is well-documented:

• In a case study of a young man with a single kidney, creatine supplementation (20g/day for 5 days, then 5g/day for 30 days) increased serum creatinine from 1.03 mg/dL to 1.27 mg/dL, decreasing estimated creatinine clearance from 88 to 71 mL/min/1.73m², despite no change in measured GFR using the gold standard 51Cr-EDTA clearance method 4
• Multiple studies confirm that creatine supplementation causes transient elevation in serum creatinine without actual kidney damage 5

Clinical Implications

This phenomenon has important implications for clinical practice:

• Misdiagnosis risk: Patients taking creatine supplements may be incorrectly diagnosed with chronic kidney disease based solely on creatinine-based eGFR 5
• Medication dosing concerns: Inaccurate assessment of kidney function could lead to inappropriate medication dosing for drugs cleared by the kidneys 2
• Unnecessary referrals: False alarms about kidney function may lead to unnecessary nephrology referrals and additional testing 3

Management Recommendations

When evaluating kidney function in patients taking creatine supplements:

1. Document supplement use: Always ask about dietary supplements, particularly creatine, when interpreting kidney function tests 2

2. Consider alternative GFR measurements:

   • Use cystatin C-based eGFR (eGFRcys) which is not affected by creatine supplementation 1
   • Consider combined creatinine-cystatin C equations (eGFRcr-cys) for better accuracy 1
   • In critical situations, use measured GFR with an exogenous marker like iohexol 6

3. Timing of assessment:

   • If possible, assess kidney function after discontinuation of creatine supplementation (may require 4-6 weeks for complete washout) 3
   • For ongoing monitoring, use consistent timing relative to supplement intake 2

Common Pitfalls to Avoid

• Overreacting to isolated eGFR changes: Small fluctuations in eGFR may represent normal physiologic variation or supplement effects rather than true kidney function changes 2
• Ignoring clinical context: Failure to consider dietary supplements when interpreting kidney function can lead to diagnostic errors 2
• Relying solely on creatinine-based eGFR: This is particularly problematic in patients with altered muscle mass or those taking supplements 2, 6

Special Considerations

• High-risk populations: Patients with pre-existing kidney disease, single kidney, or taking nephrotoxic medications should be monitored more carefully if using creatine supplements 5
• Other dietary factors: High-protein diets often accompany creatine supplementation and can further complicate interpretation of kidney function tests 1, 5

By understanding the effect of creatine supplementation on calculated GFR, clinicians can avoid unnecessary concern about kidney function and make appropriate decisions regarding further testing and management.