What is the normal range for Cystatin C (Cysteine Proteinase Inhibitor) levels in adults?

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Cystatin C Normal Ranges in Adults

The normal reference range for serum cystatin C in adults is approximately 0.50-1.02 mg/L, with values varying slightly by age and sex. 1

Age-Specific Reference Values

  • Adults aged 20-59 years:

    • Males: 0.74 ± 0.100 mg/L 2
    • Females: 0.65 ± 0.085 mg/L 2
  • Adults ≥60 years: 0.83 ± 0.103 mg/L for both sexes, reflecting physiological aging of renal function 2

  • Children aged 4-19 years: 0.75 ± 0.089 mg/L 2

Key Clinical Considerations

The most commonly cited reference interval across multiple studies is 0.51-1.02 mg/L (median 0.79 mg/L) for general adult populations. 1 However, important variations exist:

  • A large French study of 1,223 subjects demonstrated Gaussian distribution with slightly lower values in females compared to males under age 60 2

  • Saudi population data showed a mean of 0.751 ± 0.11 mg/L with a 95% reference range of 0.53-0.95 mg/L 3

  • Japanese studies reported reference intervals of 0.47-1.03 mg/L 4

Factors Affecting Cystatin C Levels

Unlike creatinine, cystatin C is largely independent of muscle mass, making it superior for patients with variable muscle mass, malnutrition, or extremes of body composition. 5

  • Age: Levels increase significantly after age 60 due to physiological decline in GFR 2

  • Sex: Females have slightly lower values than males in the 20-59 age range, but this difference disappears after age 60 2

  • Body mass index: Shows only moderate correlation without biological significance 2

  • Medications: Methylprednisolone increases levels; cyclosporin A decreases levels 2

Clinical Interpretation

Cystatin C begins to rise above normal when GFR falls below 94.4 mL/min (135.9 L/day), making it more sensitive than creatinine for detecting early renal impairment. 4 This represents a critical advantage, as serum creatinine may remain within normal ranges at this level of GFR reduction.

  • The 2012 CKD-EPI cystatin C equation uses 0.8 mg/L as the reference point in its formula for estimating GFR 6

  • KDIGO 2024 guidelines recommend cystatin C-based equations specifically for patients with stage 3a CKD (eGFR 45-59 mL/min/1.73m²) and variable muscle mass to confirm CKD diagnosis 5

Biological Variation

Cystatin C demonstrates superior biological characteristics for detecting impaired renal function compared to creatinine. 7 The critical difference for sequential measurements is 37% for cystatin C versus 14% for creatinine, with intraindividual variance accounting for 75% of cystatin C biological variation versus only 7% for creatinine 7. This means the upper limit of the reference interval for cystatin C is typically only 3-4 standard deviations from any individual's mean value, whereas for creatinine this can range from 2-13 standard deviations depending on the individual 7.

References

Research

Determination of serum cystatin C: biological variation and reference values.

Clinical chemistry and laboratory medicine, 2001

Research

Normal reference levels of serum cystatin C in Saudi adults.

Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia, 2008

Guideline

Cystatin C Testing for Accurate Kidney Function Assessment in Stage 3a CKD

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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