Abstract
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, β(2)-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 m(2)) 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 m(2)). 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 (eGFR(cr,) eGFR(cys), eGFR(B2M), and eGFR(BTP), respectively). Residual associations of factors with eGFR after accounting for measured GFR as the parameter of interest. RESULTS: eGFR(cys), eGFR(B2M), and eGFR(BTP) had significantly less strong residual associations with age and sex than eGFR(cr) 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. eGFR(cys) and eGFR(B2M), but not eGFR(BTP), 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.