What are normal levels of Cystatin C (Cysteine Proteinase Inhibitor)?

Normal Levels of Cystatin C

Normal serum cystatin C levels in adults range from 0.50 to 1.09 mg/L, with a mean of approximately 0.74-0.75 mg/L, though reference ranges should be interpreted in the context of age, sex, and the specific assay used. 1, 2, 3

Reference Ranges by Population

Adults (General Population)

• Overall adult reference range: 0.51-1.02 mg/L (median: 0.79 mg/L) 2
• Alternative reference range: 0.53-0.95 mg/L (95% of healthy subjects) 3
• Mean values in healthy adults: 0.751 ± 0.11 mg/L 3

Age-Specific Variations

• Children (4-19 years): 0.75 ± 0.089 mg/L 1
• Adults (20-59 years):
  • Males: 0.74 ± 0.100 mg/L 1
  • Females: 0.65 ± 0.085 mg/L 1
• Older adults (≥60 years): 0.83 ± 0.103 mg/L 1
• Young adults (21-30 years): 0.738 ± 0.11 mg/L 3
• Adults (>50 years): 0.807 ± 0.12 mg/L 3

Sex Differences

Cystatin C levels are slightly lower in females compared to males in adults under 60 years of age. 1 In one study, females had a mean of 0.778 ± 0.118 mg/L compared to males at 0.726 ± 0.095 mg/L (p < 0.0001). 3 However, this sex difference is much less pronounced than with creatinine, making cystatin C more independent of gender than creatinine-based markers. 4

Laboratory Reporting Standards

Measurement and Reporting Requirements

Clinical laboratories should measure cystatin C using assays with calibration traceable to international standard reference materials, with precision (coefficient of variation) <2.0% and desirable bias <3.2% compared to reference methodology. 5

• Reporting format: Cystatin C concentration should be rounded to the nearest 100th of a whole number when expressed as conventional units (mg/L) 5
• Recommended assay: Particle-enhanced nephelometric immunoassay or IFCC-traceable methods 5, 1
• Sample handling: Separate serum/plasma from red blood cells by centrifugation within 12 hours of venipuncture 5

Factors Affecting Cystatin C Levels (Independent of GFR)

Physiological Factors

• Age: Cystatin C is 4.3% lower for every 20 years of age (after adjustment for GFR), though levels increase after age 60 due to physiological aging of renal function 6, 1
• Sex: 9.2% lower in females after GFR adjustment 6
• Race: Only 1.9% lower in Black individuals 6

Pathological and Medication Factors

• Diabetes: Associated with 8.5% higher cystatin C levels (independent of GFR) 6
• Inflammation: Higher C-reactive protein and white blood cell count associated with higher cystatin C 6
• Thyroid dysfunction: Can affect cystatin C levels independent of renal function 5, 7
• Medications: Methylprednisolone increases cystatin C levels; cyclosporin A decreases levels 1
• Smoking: Moderate correlation with higher cystatin C levels 1
• Body mass index: Slight positive correlation with cystatin C 1, 3

Clinical Interpretation Context

Cystatin C should not be interpreted in isolation but rather used to calculate estimated GFR (eGFR) using validated equations, particularly the 2012 CKD-EPI cystatin C equation. 5, 8

When to Use Cystatin C

• Confirmatory testing: Adults with eGFRcreat 45-59 mL/min/1.73 m² without other markers of kidney damage 5, 8
• Altered muscle mass: Extremes of muscle mass, malnutrition, neuromuscular diseases, amputations 8
• Special populations: Liver transplant recipients, cancer patients requiring nephrotoxic drug dosing, class III obesity 5, 8

Important Caveats

Cystatin C production is constant in individuals aged 1-50 years and is produced by all nucleated cells at a steady rate, making it theoretically superior to creatinine. 4 However, hormonal status in women (puberty, menopause, oral contraceptives, hormone replacement therapy) does not significantly affect cystatin C levels. 1