Can strength training with creatine (Creatine Monohydrate) supplementation of 4.5 grams daily cause impaired renal function, as indicated by elevated Creatinine levels, abnormal Blood Urea Nitrogen (BUN)/Creatinine ratio, and decreased estimated Glomerular Filtration Rate (eGFR), in a postmenopausal woman?

Creatine and Strength Training Are Unlikely to Cause True Renal Impairment, But This Patient Has Stage 3b CKD Requiring Urgent Evaluation

The laboratory findings (creatinine 1.57 mg/dL, eGFR 37 mL/min/1.73 m², BUN/Cr ratio 8) represent Stage 3b chronic kidney disease that requires immediate discontinuation of creatine supplementation and comprehensive nephrology evaluation, as creatine is contraindicated in individuals with creatinine clearance <60 mL/min. 1

Critical Clinical Context

Serum creatinine is profoundly affected by muscle mass, making interpretation complex in this scenario. 2 The combination of strength training (which increases muscle mass) and creatine supplementation (which increases intramuscular creatine stores) can artificially elevate serum creatinine levels without indicating true renal dysfunction. 2

However, the eGFR of 37 mL/min/1.73 m² places this patient in Stage 3b CKD (moderate-to-severe decrease in GFR, range 30-59 mL/min/1.73 m²), which represents significant renal impairment regardless of the cause. 2

Key Diagnostic Considerations

The Creatinine Paradox in Athletes

• Creatine supplementation increases serum creatinine through increased muscle creatine stores and creatine metabolism, not through kidney damage. 3 This can create a false impression of renal dysfunction when using creatinine-based equations. 2

• Strength training increases muscle mass, which independently raises baseline creatinine production. 2, 4 In postmenopausal women, who typically have reduced muscle mass, this effect can be particularly pronounced when starting resistance training. 2

• The abnormally low BUN/Cr ratio of 8 (normal is typically 10-20) strongly suggests that the elevated creatinine is disproportionate to actual renal dysfunction. 2 This pattern is consistent with increased creatinine production from muscle metabolism and creatine supplementation rather than true kidney disease.

Evidence Against Creatine-Induced Nephrotoxicity

• A 12-week randomized controlled trial in postmenopausal women using creatine supplementation (20 g/day for 1 week, then 5 g/day) showed no change in measured GFR using the gold-standard ⁵¹Cr-EDTA clearance method. 5 This directly addresses the population in question.

• A 2-year randomized controlled trial of 237 postmenopausal women (mean age 59) receiving creatine (0.14 g/kg/day, approximately 9-10 g/day) with exercise showed no adverse renal effects. 6 This is the longest and highest-quality study in this exact population.

• Systematic reviews of creatine supplementation (doses 5-30 g/day for 5 days to 5 years) found no significant effects on GFR or other kidney function markers in healthy individuals. 7, 8

Mandatory Immediate Actions

Discontinue Creatine Immediately

Creatine supplementation is contraindicated in elderly individuals with creatinine clearance <60 mL/min, per American Geriatrics Society recommendations. 1 This patient's eGFR of 37 clearly falls below this threshold.

Obtain Accurate Renal Function Assessment

• Serum creatinine alone grossly underestimates renal insufficiency and should never be used as a standalone marker. 2 The patient requires calculated creatinine clearance using Cockcroft-Gault or MDRD equations. 1

• Consider cystatin C-based eGFR calculation (CKD-EPI Cr-cystatin C equation), which is more accurate than creatinine-based equations in older people with altered muscle mass. 2 This will help distinguish between true renal dysfunction and creatinine elevation from increased muscle mass.

• Measure actual GFR using ⁵¹Cr-EDTA clearance or iohexol clearance if available, as this is the gold standard and eliminates confounding from muscle mass. 5

Evaluate for Underlying Kidney Disease

• The rapid decline in eGFR over 6 months is concerning and cannot be attributed to creatine supplementation alone, given the strong safety evidence. 5, 6 This timeline suggests an alternative etiology requiring investigation.

• Assess for:

  • Pre-existing chronic kidney disease that was unmasked by increased creatinine production 1
  • Dehydration from inadequate fluid intake during exercise 4
  • Nephrotoxic medications (NSAIDs, ACE inhibitors, diuretics) 2
  • Diabetes, hypertension, or vascular disease 2
  • Urinary tract obstruction or infection 2

Clinical Algorithm for Management

1. Stop creatine supplementation immediately 1

2. Ensure adequate hydration (dehydration can falsely elevate both creatinine and reduce GFR) 4

3. Repeat renal function testing in 2-4 weeks after creatine washout (creatine has a half-life of approximately 3 hours, but tissue stores take weeks to normalize) 3

4. If eGFR remains <45 mL/min/1.73 m² after creatine washout, refer to nephrology for comprehensive evaluation including:

   • Cystatin C-based eGFR 2
   • Urinalysis with microscopy 2
   • Urine protein-to-creatinine ratio 4
   • Renal ultrasound 2

5. If eGFR normalizes after creatine discontinuation, the elevated creatinine was likely artifactual from supplementation and increased muscle mass, but the patient should not resume creatine given the initial concerning values 1

Critical Pitfalls to Avoid

• Do not assume the elevated creatinine is solely from creatine supplementation without ruling out true kidney disease. 1 An eGFR of 37 is too low to dismiss without thorough investigation.

• Do not allow the patient to continue creatine while "monitoring" renal function. 1 The contraindication is absolute with eGFR <60.

• Do not rely on serum creatinine normalization as proof of normal kidney function in someone with changing muscle mass. 2 Use cystatin C or measured GFR for accurate assessment.

• Do not overlook that postmenopausal women have reduced muscle mass and lower baseline creatinine levels (0.6-1.0 mg/dL in women vs 0.8-1.3 mg/dL in men). 2 A creatinine of 1.57 mg/dL represents a more significant elevation in this population than the absolute number suggests.