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

Research output: Contribution to journalArticle

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, 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)
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Dec 23 2016

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prostaglandin R2 D-isomerase
Blood Proteins
Molecular Weight
Cystatin C
Kidney
Glomerular Filtration Rate
Creatinine
Chronic Renal Insufficiency
Salivary Cystatins
Independent Living
C-Reactive Protein
Sample Size
Population
Atherosclerosis
Cross-Sectional Studies
Demography
Inflammation
Serum
Genes
Proteins

Keywords

  • Beta-trace protein (BTP)
  • Biomarker
  • Creatinine
  • Cystatin C
  • Elderly
  • Filtration markers
  • GFR estimation
  • Glomerular filtration rate (GFR)
  • Kidney function
  • β-microglobulin (B2M)

ASJC Scopus subject areas

  • Nephrology

Cite this

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly : AGES-Kidney and MESA-Kidney. / Foster, Meredith C.; Levey, Andrew S.; Inker, Lesley A.; Shafi, Tariq; Fan, Li; Gudnason, Vilmundur; Katz, Ronit; Mitchell, Gary F.; Okparavero, Aghogho; Palsson, Runolfur; Post, Wendy S; Shlipak, Michael G.

In: American Journal of Kidney Diseases, 23.12.2016.

Research output: Contribution to journalArticle

Foster, MC, Levey, AS, Inker, LA, Shafi, T, Fan, L, Gudnason, V, Katz, R, Mitchell, GF, Okparavero, A, Palsson, R, Post, WS & Shlipak, MG 2016, 'Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly: AGES-Kidney and MESA-Kidney', American Journal of Kidney Diseases. https://doi.org/10.1053/j.ajkd.2017.03.021
Foster, Meredith C. ; Levey, Andrew S. ; Inker, Lesley A. ; Shafi, Tariq ; Fan, Li ; Gudnason, Vilmundur ; Katz, Ronit ; Mitchell, Gary F. ; Okparavero, Aghogho ; Palsson, Runolfur ; Post, Wendy S ; Shlipak, Michael G. / Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly : AGES-Kidney and MESA-Kidney. In: American Journal of Kidney Diseases. 2016.
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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, 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.",
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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.

PY - 2016/12/23

Y1 - 2016/12/23

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 - Beta-trace protein (BTP)

KW - Biomarker

KW - Creatinine

KW - Cystatin C

KW - Elderly

KW - Filtration markers

KW - GFR estimation

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

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

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