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

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 (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.