Can long-term creatine (Creatine Monohydrate) supplementation lead to a false indication of stage 3b Chronic Kidney Disease (CKD)?

Can Creatine Supplementation Cause False Stage 3B CKD?

Yes, long-term creatine supplementation can cause a false indication of stage 3B CKD by elevating serum creatinine levels without actually impairing kidney function, but this does not represent true kidney disease.

Understanding the Mechanism of False Elevation

Creatine supplementation increases serum creatinine through non-pathological mechanisms that do not reflect actual kidney dysfunction 1, 2:

• Creatine spontaneously converts to creatinine in the body, leading to elevated serum creatinine levels that are unrelated to glomerular filtration rate 2, 3
• This elevation can falsely lower the estimated GFR (eGFR) calculated from creatinine-based equations, potentially misclassifying individuals as having CKD stage 3B (eGFR 30-44 mL/min/1.73 m²) 1
• In one case study, a young man with a single kidney showed serum creatinine increase from 1.03 to 1.27 mg/dL after creatine supplementation, while actual measured GFR remained unchanged (81.6 vs 82.0 mL/min/1.73 m²) 1

Clinical Evidence on Actual Kidney Function

Multiple studies demonstrate that creatine does not impair true kidney function 4, 5, 3:

• Short-term supplementation (5 days to 2 weeks at 20-30 g/day) and long-term supplementation (up to 5 years at 5 g/day) show no significant effects on actual glomerular filtration rate in healthy individuals 4
• When measured by gold-standard methods (like ⁵¹Cr-EDTA clearance or inulin clearance), GFR remains stable despite elevated serum creatinine 1
• Proteinuria, electrolyte levels, and other markers of kidney damage remain unchanged with creatine supplementation 1

How to Confirm True Kidney Function

When creatine supplementation is suspected of causing false CKD staging, use confirmatory testing per KDIGO guidelines 6:

• Measure cystatin C in patients with eGFR 30-59 mL/min/1.73 m² without other markers of kidney damage 6
• If cystatin C-based eGFR is >60 mL/min/1.73 m², the diagnosis of CKD is not confirmed 6
• However, note that even cystatin C strategies show 26-30% misclassification rates in the 30-45 mL/min/1.73 m² range 6
• Gold standard testing with measured GFR (inulin clearance or iothalamate clearance) provides definitive assessment 1

Additional Confounding Factors

The false elevation can be compounded by dietary factors 2:

• High protein diets (common among creatine users) independently increase blood urea nitrogen, further mimicking kidney dysfunction 2
• This combination can lead to overdiagnosis of chronic renal failure with significant personal and public health consequences 2

Safety Profile and Precautions

Creatine supplementation is safe for individuals without pre-existing kidney disease 4, 5, 3:

• Contraindications: Avoid creatine in patients with pre-existing chronic kidney disease, diabetes, hypertension, reduced baseline GFR, or those taking potentially nephrotoxic medications 5
• Monitoring: Consider baseline kidney function assessment before supplementation in at-risk individuals, though unnecessary in healthy subjects 5
• Reports of actual kidney damage from creatine are scanty and lack causal evidence 2, 3

Clinical Pitfalls to Avoid

• Do not diagnose CKD based solely on creatinine-based eGFR in patients taking creatine supplements 1, 2
• Always obtain a supplement history before diagnosing new-onset CKD, specifically asking about creatine use 2
• Discontinue creatine temporarily (2-4 weeks) and recheck creatinine to see if levels normalize, confirming the false elevation 2
• Use cystatin C or measured GFR for definitive assessment rather than relying on creatinine-based equations alone 6