Why are creatinine (kidney function test) and albumin (liver function test) levels elevated in a young, otherwise healthy female with normal Glomerular Filtration Rate (GFR)?

Elevated Creatinine and Albumin with Normal GFR: Understanding the Discrepancy

In a young, healthy female with normal GFR but elevated creatinine and albumin, the most likely explanation is exogenous creatine intake (dietary supplements or high meat consumption) causing falsely elevated serum creatinine, while the elevated albumin represents either transient physiologic variation or early kidney damage that hasn't yet reduced GFR. 1, 2, 3

Why Creatinine Can Be Elevated Despite Normal GFR

Non-Renal Causes of Elevated Creatinine

Serum creatinine reflects both endogenous muscle production and exogenous dietary intake, making it susceptible to false elevations that don't represent true kidney dysfunction. 2 The most common causes include:

• Creatine supplementation: Creatine supplements can increase serum creatinine by 0.2-0.3 mg/dL through non-pathologic conversion to creatinine, creating a false appearance of acute kidney injury. 2, 4 In one case, creatine supplementation increased serum creatinine from 1.03 to 1.27 mg/dL while measured GFR remained completely unchanged. 2

• High dietary meat intake: Creatine and creatinine from dietary muscle meat (particularly red meat and beef liver) can temporarily elevate serum creatinine levels without indicating kidney damage. 2, 3 One infant presented with markedly elevated creatinine from homemade formula containing beef liver, which normalized within 12 hours of stopping the formula. 3

• High muscle mass: eGFR formulas incorporating serum creatinine are unreliable in patients with high muscle mass, as creatinine production is directly proportional to muscle mass. 2, 5

Critical Limitation of eGFR Calculations

eGFR calculations assume steady-state conditions and are invalid when creatinine is acutely elevated from non-renal causes such as creatine supplementation and intense exercise. 2 This explains why the calculated GFR appears normal—the formula is attempting to "correct" for what it interprets as increased creatinine production, when in reality the elevation is exogenous. 1, 2

Why Albumin Can Be Elevated

Physiologic and Transient Causes

Albumin excretion demonstrates high within-individual variability, with a repeated measurement potentially being as high as 3.78 times or as low as 0.26 times the first measurement. 6 Several factors can cause transient elevations:

• Exercise within 24 hours of urine collection can elevate urinary albumin excretion over baseline values. 7
• Dehydration and concentrated urine can falsely elevate albumin-to-creatinine ratio measurements. 2
• Fever, infection, or marked hyperglycemia may temporarily increase albumin excretion. 7
• Postural (orthostatic) proteinuria, particularly in young patients, can be a confounding factor. 7

Early Kidney Damage with Preserved GFR

At any level of GFR, an albumin-to-creatinine ratio increase above normal is associated with increased risk for adverse outcomes, and this risk exists on a continuum. 7 Importantly:

• In patients with elevated urinary albumin excretion, loss of GFR within CKD stage 1 (GFR >90 mL/min) may already represent diabetic kidney disease. 7
• Albumin is the most important protein lost in the urine in most cases of CKD, and urinary albumin-to-creatinine ratio accurately predicts kidney and cardiovascular risks even when GFR remains normal. 7

Diagnostic Approach to Resolve the Discrepancy

Immediate Steps

1. Obtain a detailed dietary and supplement history, specifically asking about creatine supplements, protein powders, pre-workout supplements, and high meat consumption. 2, 4

2. Check spot urine albumin-to-creatinine ratio to confirm albuminuria, as albumin concentration alone is susceptible to false results from hydration status. 7, 2

3. Measure cystatin C as an alternative marker of kidney function that is unaffected by muscle mass, diet, or creatine supplementation. 2 If cystatin C-based eGFR is normal, this strongly suggests the elevated creatinine is non-renal in origin. 3

4. Obtain urinalysis with microscopy to look for proteinuria, hematuria, cellular casts, or acanthocytes that would indicate true intrinsic kidney disease. 2

Confirmation Testing

Because of variability in urinary albumin excretion, two of three specimens collected within a 3- to 6-month period should be abnormal before considering a patient to have developed albuminuria. 7 For creatinine assessment:

• If creatine supplementation is identified, discontinue it immediately and repeat serum creatinine within 1-2 weeks to assess true baseline kidney function. 2, 4
• Maintain consistent hydration and fast from meat for 12-24 hours before repeat creatinine testing to avoid dietary effects. 2
• Avoid intense exercise 24 hours prior to testing, as muscle breakdown releases creatinine. 2

Common Pitfalls to Avoid

Never use serum creatinine alone to assess kidney function due to multiple confounding factors including diet, muscle mass, hydration status, and medications. 2 Additionally:

• Small creatinine changes (0.3 mg/dL) may represent physiologic fluctuation or dietary variation rather than true GFR reduction. 2
• A single elevated creatinine in the context of creatine supplementation and recent exercise does not establish CKD diagnosis, which requires evidence of kidney damage or reduced GFR persisting for at least 3 months. 2
• Measurement of albumin concentration alone without simultaneously measuring urine creatinine is susceptible to false determinations due to variation in urine concentration. 7