Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly: AGES-Kidney and MESA-Kidney

Meredith C. Foster, Andrew S. Levey, Lesley A. Inker, Tariq Shafi, Li Fan, Vilmundur Gudnason, Ronit Katz, Gary F. Mitchell, Aghogho Okparavero, Runolfur Palsson, Wendy S. Post, Michael G. Shlipak

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47 Scopus citations


Background Studies in chronic kidney disease populations suggest that the non–glomerular filtration rate (GFR) determinants of serum levels of the low-molecular-weight protein filtration markers cystatin C, β2-microglobulin (B2M), and beta-trace protein (BTP) are less affected by age, sex, and ethnicity than those of creatinine. Study Design Cross-sectional study. Setting & Participants Predominantly elderly participants selected from the Age, Gene/Environment Susceptibility Kidney Study (AGES-Kidney; N = 683; mean [SD] age, 79 [4] years; GFR, 62 [17] mL/min/1.73 m2) and from the Multi-Ethnic Study of Atherosclerosis Kidney Study (MESA-Kidney; N = 273; mean [SD] age, 70.5 [9] years; GFR, 73 [19] mL/min/1.73 m2). Predictors Demographic and clinical factors hypothesized to be associated with conditions affecting non-GFR determinants of the filtration markers. Outcomes Measured GFRs and estimated GFRs (eGFRs) based on creatinine, cystatin C, B2M, and BTP levels (eGFRcr eGFRcys, eGFRB2M, and eGFRBTP, respectively). Residual associations of factors with eGFR after accounting for measured GFR as the parameter of interest. Results eGFRcys, eGFRB2M, and eGFRBTP had significantly less strong residual associations with age and sex than eGFRcr in both AGES-Kidney and MESA-Kidney and were not associated with ethnicity (black vs white) in MESA-Kidney. After adjusting for age, sex, and ethnicity, residual associations with most clinical factors were smaller than observed with age and sex. eGFRcys and eGFRB2M, but not eGFRBTP, had significant residual associations with C-reactive protein levels in both studies. Limitations Small sample size may limit power to detect associations. Participants may be healthier than the general population. Conclusions Similar to previous studies in chronic kidney disease, in community-dwelling elders, cystatin C, B2M, and BTP levels are less affected than creatinine level by age and sex and are not affected by ethnicity. Both cystatin C and B2M levels may be affected by inflammation. These findings are important for the development and use of GFR estimating equations based on low-molecular-weight serum proteins throughout the range in GFRs.

Original languageEnglish (US)
Pages (from-to)406-414
Number of pages9
JournalAmerican Journal of Kidney Diseases
Issue number3
StatePublished - Sep 2017


  • Filtration markers
  • GFR estimation
  • beta-trace protein (BTP)
  • biomarker
  • creatinine
  • cystatin C
  • elderly
  • glomerular filtration rate (GFR)
  • kidney function
  • β-microglobulin (B2M)

ASJC Scopus subject areas

  • Nephrology


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