Can long-term creatine (Creatine Monohydrate) supplementation and intense exercise cause impaired renal function, as indicated by elevated creatinine levels, low estimated Glomerular Filtration Rate (eGFR) of 37, and a Blood Urea Nitrogen (BUN)/creatinine ratio of 8 in a muscular patient?

Likelihood Assessment: Creatine Supplementation and Exercise Effects on Renal Function Parameters

In a muscular patient with recent intense exercise and long-term creatine supplementation, the observed elevated creatinine, eGFR of 37, and BUN/creatinine ratio of 8 is highly likely to represent a false elevation in serum creatinine rather than true renal impairment, but this requires immediate confirmation with cystatin C-based eGFR testing.

Key Diagnostic Considerations

Why This is Likely NOT True Renal Impairment

The clinical presentation strongly suggests falsely elevated creatinine due to non-GFR determinants rather than actual kidney disease:

• High muscle mass is a well-established cause of elevated serum creatinine independent of kidney function, as creatinine generation is directly proportional to skeletal muscle mass 1
• Creatine supplementation specifically increases creatinine production as creatine is converted to creatinine in the body, causing falsely elevated serum creatinine concentrations that do not reflect true renal dysfunction 1, 2
• Recent intense exercise (within 2 days) can transiently elevate creatinine levels through increased muscle metabolism and breakdown 1, 3
• The BUN/creatinine ratio of 8 is abnormally LOW (normal is 10-20), which argues strongly against true renal disease and instead suggests isolated creatinine elevation from increased creatinine generation 3

Critical Guideline-Based Evidence

The KDIGO 2024 guidelines explicitly identify this exact clinical scenario as requiring cystatin C testing:

• High-protein diets and creatine supplements are specifically listed as conditions where serum creatinine-based eGFR is inaccurate due to non-GFR determinants 1
• Extreme sport/exercise/bodybuilders with increased muscle mass should use eGFRcys (cystatin C-based) if muscle increase is the only abnormality 1
• Serum creatinine concentration should never be used alone to assess kidney function, particularly in individuals with extremes of muscle mass 1

Immediate Diagnostic Algorithm

Step 1: Order Cystatin C Testing Immediately

• Measure serum cystatin C and calculate eGFRcr-cys (combined creatinine-cystatin C equation) 1
• Cystatin C is not affected by muscle mass or creatine supplementation, making it the ideal confirmatory test in this scenario 1
• If eGFRcys is normal (>60 mL/min/1.73 m²), this confirms the elevated creatinine is spurious 1

Step 2: Assess for True Kidney Disease Markers

Check for markers that would indicate actual kidney damage:

• Urinary albumin-to-creatinine ratio (UACR): Normal is <30 mg/g creatinine; elevation suggests true kidney disease 1, 3
• Urinalysis: Look for proteinuria, hematuria, or abnormal sediment that would indicate intrinsic kidney disease 3
• Repeat measurements: Ensure exercise was not performed within 24 hours before testing, as this can falsely elevate UACR 1, 3

Step 3: Temporarily Discontinue Creatine and Retest

• Stop creatine supplementation for 2-4 weeks and remeasure serum creatinine 4, 2, 5
• If creatinine normalizes, this confirms the supplement was the cause 4, 2
• Avoid intense exercise for 48-72 hours before retesting 1, 3

Evidence on Creatine Safety

Reassuring Data on Renal Function

Multiple high-quality studies demonstrate creatine supplementation does not cause true renal dysfunction:

• A 2019 systematic review and meta-analysis found creatine supplementation did not significantly alter serum creatinine or plasma urea and does not induce renal damage in studied amounts and durations 6
• Studies of both short-term (5 days) and long-term (up to 5.6 years) supplementation showed no significant effects on glomerular filtration rate in healthy individuals without underlying kidney disease 7, 5
• Creatine supplements are safe and do not cause renal disease in healthy individuals, though they may transiently raise serum creatinine and mimic kidney disease 2

Important Caveats

• One case report described acute tubular necrosis in an 18-year-old taking creatine, though this is extremely rare and not definitively causal 4
• Creatine should not be used in individuals with pre-existing chronic kidney disease or those taking potentially nephrotoxic medications 7, 2

Clinical Pitfalls to Avoid

Do Not Over-Diagnose CKD Based on Creatinine Alone

• Serum creatinine-based eGFR is misleading in muscular individuals, potentially leading to false diagnosis of chronic kidney disease with significant personal and public health consequences 1, 2
• The elderly and those with reduced muscle mass have falsely reassuring creatinine levels, while muscular individuals have falsely elevated levels 1
• GFR must decline to approximately half normal before serum creatinine rises above the upper limit of normal in average individuals 1

Recognize the Low BUN/Creatinine Ratio

• A ratio of 8 is significantly below the normal range of 10-20, strongly suggesting isolated creatinine elevation rather than true renal dysfunction 3
• In true renal disease, BUN typically rises proportionally or disproportionately to creatinine 3
• This low ratio is a key distinguishing feature pointing away from intrinsic kidney injury 3

When to Refer to Nephrology

According to KDIGO guidelines, referral is indicated for:

• eGFR <30 mL/min/1.73 m² (this patient has eGFR 37, just above this threshold) 1
• Uncertainty about etiology of kidney disease 1
• Rapidly progressing kidney disease 1

However, if cystatin C-based eGFR is normal and UACR is normal, nephrology referral is likely unnecessary as this represents spurious creatinine elevation rather than true kidney disease 1.

Bottom Line

The combination of high muscle mass, creatine supplementation, and recent intense exercise makes spurious creatinine elevation extremely likely. The abnormally low BUN/creatinine ratio of 8 further supports this interpretation. Cystatin C testing is mandatory to distinguish false from true renal impairment before any clinical decisions are made 1. Creatine supplementation itself does not cause true kidney damage in healthy individuals 7, 6, 5.