Comparison of serum concentrations of β-trace protein, β2-microglobulin, cystatin C, and creatinine in the US population

Clin J Am Soc Nephrol. 2013 Apr;8(4):584-92. doi: 10.2215/CJN.08700812. Epub 2013 Jan 18.


Background and objectives: β-trace protein (βTP), β2-microglobulin (β2M), and cystatin C (CysC) have advantages over creatinine for estimating GFR and prognosis. This study compares the distribution of all four markers in the general population and their associations with possible determinants of GFR.

Design, setting, participants, & measurements: βTP and β2M were measured in 7596 participants (aged ≥12 years) of the Third National Health and Nutrition Examination Survey (1988-1994). βTP and β2M concentrations and the proportion of persons with elevated (≥99th percentile for young healthy participants) βTP (≥0.81 mg/L), β2M (≥2.80 mg/L), standardized CysC (≥1.03 mg/L), and creatinine (≥1.2 mg/dl for men and ≥1.0 mg/dl for women) were compared across demographic and clinical factors.

Results: Elevated βTP, β2M, and CysC showed stronger associations with age than elevated serum creatinine, the prevalence of elevated levels reaching 47%, 44%, 58%, and 26%, respectively, by age 80 years. βTP, CysC, and creatinine were higher in men but β2M was not associated with sex. Mexican Americans had lower βTP, β2M, CysC, and creatinine compared with non-Hispanic whites. Hypertension and higher C-reactive protein were associated with elevations in all markers, whereas non-Hispanic black race, body mass index, diabetes, smoking status, triglycerides, HDL cholesterol, and education were not associated in a consistent manner across the different markers.

Conclusions: βTP, β2M, CysC, and creatinine differ in their associations with demographic and clinical factors, suggesting variation in their non-GFR determinants. Future studies should examine these markers with measured GFR to determine their diagnostic and prognostic utility.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Child
  • Creatinine / blood*
  • Cystatin C / blood*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Intramolecular Oxidoreductases / blood*
  • Lipocalins / blood*
  • Male
  • Middle Aged
  • Nutrition Surveys / statistics & numerical data
  • Outcome Assessment, Health Care
  • Prognosis
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / epidemiology*
  • Risk Factors
  • United States / epidemiology
  • Young Adult
  • beta 2-Microglobulin / blood*


  • Biomarkers
  • Cystatin C
  • Lipocalins
  • beta 2-Microglobulin
  • Creatinine
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase