What is creatinine?

Understanding Creatinine in Clinical Practice

Creatinine is an endogenous compound primarily produced from muscle catabolism that serves as a marker of kidney function, though it has significant limitations when used alone to assess renal function. 1

What is Creatinine?

Creatinine is:

• An endogenous compound produced mainly from muscle catabolism and released into the blood 1
• Relatively stable in production for a given individual 1
• Primarily eliminated through glomerular filtration in the kidneys 1
• Measured in serum as µmol/L or mg/dL (conversion: µmol/L = mg/dL × 88.4) 1

Normal Reference Ranges

• Men: 0.8 to 1.3 mg/dL (70–115 µmol/L) 1
• Women: 0.6 to 1.0 mg/dL (55–90 µmol/L) 1

Limitations of Serum Creatinine

Serum creatinine has significant limitations as a standalone marker of kidney function:

1. Non-linear relationship with GFR: When serum creatinine significantly increases, GFR has already decreased by at least 40% 1

2. Influenced by multiple factors:

   • Acute factors affecting creatinine 1:

     • Dietary creatine intake (meat meals)
     • Rhabdomyolysis (increased generation)
     • Acute kidney injury
     • Medications that reduce tubular secretion (trimethoprim, cimetidine)

   • Chronic factors affecting creatinine 1:

     • Muscle mass (higher in muscular individuals, lower in elderly)
     • Age and sex (lower in elderly and females)
     • Ethnicity (higher in Afro-Caribbean individuals)
     • Chronic kidney disease
     • Muscle-wasting conditions, amputation, malnutrition
     • Low dietary protein intake

3. Laboratory interference:

   • Jaffe assay interference with hyperbilirubinemia
   • Enzymatic interference from hyperbilirubinemia and hemolysis 1

Clinical Significance

Kidney Function Assessment

• The National Kidney Foundation recommends against relying solely on serum creatinine without calculating creatinine clearance 2
• When serum creatinine increases significantly, GFR has already decreased by at least 40% 1
• Among cancer patients with normal serum creatinine, approximately 20% may have asymptomatic renal insufficiency 1

Estimating GFR

For proper assessment of kidney function:

1. Estimated GFR (eGFR) is derived from serum creatinine using formulas that include age, sex, and ethnicity 1

   • Common formulas: MDRD and CKD-EPI
   • Valid for monitoring renal function over months and years
   • Not ideal for acute changes in renal function

2. Creatinine Clearance (CrCl) can be estimated using the Cockcroft-Gault formula:

   • CrCl (mL/min) = [(140 - age) × weight in kg] / [72 × serum creatinine in mg/dL] 2
   • For women, multiply the result by 0.85

3. Alternative methods when more accurate assessment is needed:

   • 24-hour urine collection for measured creatinine clearance
   • Cystatin C measurement (less affected by muscle mass) 2

Interpreting Changes in Creatinine

• Trend is often more important than absolute value: A rising creatinine over time is more concerning than a stable elevated value 1
• Reference Change Value (RCV): A change of 14-17% in creatinine is considered clinically significant 1
• Biological variability: Small absolute increases in creatinine have different significance depending on baseline value 1

Common Pitfalls in Creatinine Interpretation

1. Assuming normal kidney function based on normal creatinine: Especially problematic in elderly patients and those with reduced muscle mass 2

2. Not considering non-renal factors: Muscle mass, diet, medications can all affect creatinine levels without reflecting changes in kidney function 1

3. Using serum creatinine alone for medication dosing: Can lead to inappropriate dosing, especially in elderly or malnourished patients 2

4. Misinterpreting acute changes: eGFR formulas are not validated for acute changes in kidney function 1

Best Practices for Creatinine Interpretation

1. Always calculate GFR or creatinine clearance rather than relying on serum creatinine alone 1, 2

2. Consider patient-specific factors that might affect creatinine production (age, sex, muscle mass, diet) 1

3. Monitor trends in creatinine values rather than isolated measurements 1

4. Use alternative markers (cystatin C) when more accurate assessment is needed, especially in patients with altered muscle mass 2

5. Adjust medication dosing based on calculated creatinine clearance, not serum creatinine alone 2