Is creatine supplementation safe for patients with impaired renal function, specifically those with concerns about their estimated Glomerular Filtration Rate (eGFR)?

Creatine Supplementation and eGFR

Creatine supplementation does not cause kidney damage in individuals with normal or mildly reduced kidney function, but it artificially elevates serum creatinine levels, which falsely lowers calculated eGFR and can lead to misdiagnosis of kidney disease. 1, 2

Understanding the Mechanism

The key issue is that creatine supplementation affects creatinine generation—a non-GFR determinant—not actual kidney function. 3

• Creatine supplements increase serum creatinine through enhanced creatine metabolism and muscle creatinine production, independent of any change in actual glomerular filtration rate 4, 2
• The KDIGO 2024 guidelines specifically identify "high-protein diets and creatine supplements" as causes of non-GFR determinants of serum creatinine that reduce the accuracy of creatinine-based eGFR equations 3
• This creates a false appearance of kidney impairment when using standard eGFRcr calculations 5, 2

Clinical Approach to Patients on Creatine

When evaluating kidney function in patients taking creatine supplements, use cystatin C-based eGFR (eGFRcys) or combined creatinine-cystatin C equations (eGFRcr-cys) rather than creatinine-based eGFR alone. 3

Recommended Testing Strategy:

• For patients on creatine supplements, eGFRcys is the preferred initial alternative since it is not affected by creatine metabolism 3
• If eGFRcys is unavailable or if comorbid illness exists, use eGFRcr-cys for more accurate assessment 3
• If precise GFR measurement is needed for critical clinical decisions, measure GFR directly using plasma or urinary clearance of exogenous filtration markers 3

Safety Evidence in Reduced Kidney Function

Short-term creatine supplementation appears safe even in individuals with mildly reduced kidney function, including those with solitary kidneys. 4

• A prospective study of a 20-year-old man with a single kidney and baseline eGFR of 81.6 mL/min/1.73 m² showed no change in measured GFR (51Cr-EDTA clearance) after 35 days of creatine supplementation (20 g/day for 5 days, then 5 g/day for 30 days) 4
• Proteinuria remained unchanged (pre: 130 mg/day; post: 120 mg/day), and albuminuria actually decreased 4
• Serum creatinine increased from 1.03 to 1.27 mg/dL, while estimated creatinine clearance falsely decreased from 88 to 71 mL/min/1.73 m², but measured GFR remained stable at 82.0 mL/min/1.73 m² 4

Contraindications and Cautions

Creatine supplementation should be avoided in patients with Stage 4-5 CKD (eGFR <30 mL/min/1.73 m²) and those taking potentially nephrotoxic medications. 1, 2

• The American College of Cardiology recommends that individuals with eGFR <30 mL/min/1.73 m² avoid supplements that increase renal workload, including creatine 1
• Patients with Stage 4 CKD (eGFR 15-29 mL/min/1.73 m²) have severely decreased kidney function with reduced renal reserve 1
• Creatine supplementation combined with high-protein diets further elevates blood urea nitrogen, compounding diagnostic confusion 2

Common Pitfall: Misdiagnosis of CKD

The most significant clinical error is misdiagnosing chronic kidney disease based on elevated creatinine from creatine supplementation alone. 5, 2

• A case report described a 54-year-old woman referred for declining eGFR who had no complaints and normal kidney function—the only abnormality was creatine supplement use 5
• After cessation of creatine supplementation, calculated renal function normalized completely 5
• This can lead to unnecessary nephrology referrals, patient anxiety, and inappropriate medical interventions 2

Practical Algorithm

1. If patient is on creatine and eGFRcr appears reduced: Order cystatin C and calculate eGFRcys or eGFRcr-cys 3

2. If eGFRcys is normal: Reassure patient that kidney function is intact; the elevated creatinine is expected from creatine supplementation 4, 5

3. If eGFRcys is also reduced: Investigate for true kidney disease with additional testing (urinalysis, imaging, etc.) 3

4. For patients with baseline eGFR >60 mL/min/1.73 m²: Creatine supplementation is safe; use eGFRcys for monitoring 4, 2

5. For patients with eGFR 30-60 mL/min/1.73 m² (Stage 3 CKD): Creatine may be used cautiously with close monitoring using cystatin C-based equations 4, 2

6. For patients with eGFR <30 mL/min/1.73 m² (Stage 4-5 CKD): Avoid creatine supplementation 1, 2