TY - JOUR
T1 - Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly
T2 - AGES-Kidney and MESA-Kidney
AU - Foster, Meredith C.
AU - Levey, Andrew S.
AU - Inker, Lesley A.
AU - Shafi, Tariq
AU - Fan, Li
AU - Gudnason, Vilmundur
AU - Katz, Ronit
AU - Mitchell, Gary F.
AU - Okparavero, Aghogho
AU - Palsson, Runolfur
AU - Post, Wendy S.
AU - Shlipak, Michael G.
N1 - Funding Information:
Support: AGES-Kidney was supported by a grant from the National Institutes of Health (NIH; R01 DK082447), contract from the National Institute on Aging (N01-AG-1-2100 and HHSN27120120022C), the Icelandic Heart Association (Hjartavernd) and the Icelandic Parliament (Althingi), and the American Recovery Act (3R01DK082447-01A1S1). MESA-Kidney was supported by R01DK087961. MESA was supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040 and UL1-TR-001079 from National Center for Research Resources. The CKD-EPI (CKD Epidemiology Collaboration) was supported by NIH grant R01DK097020. This work was supported by a research grant from Dialysis Clinic, Inc (DCI research grant #S-2607). The funding agencies had no role in the study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.
Publisher Copyright:
© 2017 National Kidney Foundation, Inc.
PY - 2017/9
Y1 - 2017/9
N2 - 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.
AB - 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.
KW - Filtration markers
KW - GFR estimation
KW - beta-trace protein (BTP)
KW - biomarker
KW - creatinine
KW - cystatin C
KW - elderly
KW - glomerular filtration rate (GFR)
KW - kidney function
KW - β-microglobulin (B2M)
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U2 - 10.1053/j.ajkd.2017.03.021
DO - 10.1053/j.ajkd.2017.03.021
M3 - Article
C2 - 28549536
AN - SCOPUS:85019553221
VL - 70
SP - 406
EP - 414
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
SN - 0272-6386
IS - 3
ER -