GFR Estimation Using β-Trace Protein and β2-Microglobulin in CKD

Lesley A. Inker, Hocine Tighiouart, Josef Coresh, Meredith C. Foster, Amanda H. Anderson, Gerald J. Beck, Gabriel Contreras, Tom Greene, Amy B. Karger, John W. Kusek, James Lash, Julia Lewis, Jeffrey R. Schelling, Sankar D. Navaneethan, James Sondheimer, Tariq Shafi, Andrew S. Levey

Research output: Contribution to journalArticle

Abstract

Background β-Trace protein (BTP) and β2-microglobulin (B2M) are novel glomerular filtration markers that have stronger associations with adverse outcomes than creatinine. Comparisons of BTP and B2M to creatinine and cystatin C are limited by the absence of rigorously developed glomerular filtration rate (GFR) estimating equations for the novel markers. Study Design Study of diagnostic test accuracy. Setting & Participants Pooled database of 3 populations with chronic kidney disease (CKD) with mean measured GFR of 48 mL/min/1.73 m2 (N = 3,551; MDRD [Modification of Diet in Renal Disease] Study, AASK [African American Study of Kidney Disease and Hypertension], and CRIC [Chronic Renal Insufficiency Cohort] Study). Index Tests GFR estimated using creatinine, cystatin C, BTP, or B2M level. Reference Test GFR measured as the urinary clearance of iothalamate. Results For BTP and B2M, coefficients for age, sex, and race were smaller than for creatinine and were similar or smaller than for cystatin C. For B2M, coefficients for sex, age, and race were smaller than for creatinine and were similar (age and race) or smaller (sex) than for cystatin C. The final equations with BTP (BTP, age, and sex) or B2M (B2M alone) were less accurate than either the CKD-EPI (CKD Epidemiology Collaboration) creatinine or cystatin C equations. The combined BTP-B2M equation (BTP and B2M alone) had similar accuracy to the CKD-EPI creatinine or cystatin C equation. The average of the BTP-B2M equation and the CKD-EPI creatinine-cystatin C equation was not more accurate than the CKD-EPI creatinine-cystatin C equation. Limitations No external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race. Conclusions BTP and B2M are less influenced by age, sex, and race than creatinine and less influenced by race than cystatin C, but provide less accurate GFR estimates than the CKD-EPI creatinine and cystatin C equations. The CKD-EPI BTP and B2M equation provides a methodological advance for their study as filtration markers and in their associations with risk and adverse outcomes, but further study is required before clinical use.

Original languageEnglish (US)
Pages (from-to)40-48
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume67
Issue number1
DOIs
StatePublished - Jan 1 2016

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Cystatin C
Glomerular Filtration Rate
Chronic Renal Insufficiency
Creatinine
Proteins
Iothalamic Acid
Population
Diet Therapy
Validation Studies
Kidney Diseases
Routine Diagnostic Tests
African Americans
Renal Insufficiency
Epidemiology
Cohort Studies
Outcome Assessment (Health Care)
Databases
Hypertension
Kidney

Keywords

  • beta-2-microglobulin (B2M)
  • Beta-trace protein (BTP)
  • chronic kidney disease (CKD)
  • diagnostic accuracy
  • estimated glomerular filtration rate (eGFR)
  • estimating equation
  • filtration marker
  • kidney function
  • measured GFR

ASJC Scopus subject areas

  • Nephrology

Cite this

Inker, L. A., Tighiouart, H., Coresh, J., Foster, M. C., Anderson, A. H., Beck, G. J., ... Levey, A. S. (2016). GFR Estimation Using β-Trace Protein and β2-Microglobulin in CKD. American Journal of Kidney Diseases, 67(1), 40-48. https://doi.org/10.1053/j.ajkd.2015.07.025

GFR Estimation Using β-Trace Protein and β2-Microglobulin in CKD. / Inker, Lesley A.; Tighiouart, Hocine; Coresh, Josef; Foster, Meredith C.; Anderson, Amanda H.; Beck, Gerald J.; Contreras, Gabriel; Greene, Tom; Karger, Amy B.; Kusek, John W.; Lash, James; Lewis, Julia; Schelling, Jeffrey R.; Navaneethan, Sankar D.; Sondheimer, James; Shafi, Tariq; Levey, Andrew S.

In: American Journal of Kidney Diseases, Vol. 67, No. 1, 01.01.2016, p. 40-48.

Research output: Contribution to journalArticle

Inker, LA, Tighiouart, H, Coresh, J, Foster, MC, Anderson, AH, Beck, GJ, Contreras, G, Greene, T, Karger, AB, Kusek, JW, Lash, J, Lewis, J, Schelling, JR, Navaneethan, SD, Sondheimer, J, Shafi, T & Levey, AS 2016, 'GFR Estimation Using β-Trace Protein and β2-Microglobulin in CKD', American Journal of Kidney Diseases, vol. 67, no. 1, pp. 40-48. https://doi.org/10.1053/j.ajkd.2015.07.025
Inker, Lesley A. ; Tighiouart, Hocine ; Coresh, Josef ; Foster, Meredith C. ; Anderson, Amanda H. ; Beck, Gerald J. ; Contreras, Gabriel ; Greene, Tom ; Karger, Amy B. ; Kusek, John W. ; Lash, James ; Lewis, Julia ; Schelling, Jeffrey R. ; Navaneethan, Sankar D. ; Sondheimer, James ; Shafi, Tariq ; Levey, Andrew S. / GFR Estimation Using β-Trace Protein and β2-Microglobulin in CKD. In: American Journal of Kidney Diseases. 2016 ; Vol. 67, No. 1. pp. 40-48.
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abstract = "Background β-Trace protein (BTP) and β2-microglobulin (B2M) are novel glomerular filtration markers that have stronger associations with adverse outcomes than creatinine. Comparisons of BTP and B2M to creatinine and cystatin C are limited by the absence of rigorously developed glomerular filtration rate (GFR) estimating equations for the novel markers. Study Design Study of diagnostic test accuracy. Setting & Participants Pooled database of 3 populations with chronic kidney disease (CKD) with mean measured GFR of 48 mL/min/1.73 m2 (N = 3,551; MDRD [Modification of Diet in Renal Disease] Study, AASK [African American Study of Kidney Disease and Hypertension], and CRIC [Chronic Renal Insufficiency Cohort] Study). Index Tests GFR estimated using creatinine, cystatin C, BTP, or B2M level. Reference Test GFR measured as the urinary clearance of iothalamate. Results For BTP and B2M, coefficients for age, sex, and race were smaller than for creatinine and were similar or smaller than for cystatin C. For B2M, coefficients for sex, age, and race were smaller than for creatinine and were similar (age and race) or smaller (sex) than for cystatin C. The final equations with BTP (BTP, age, and sex) or B2M (B2M alone) were less accurate than either the CKD-EPI (CKD Epidemiology Collaboration) creatinine or cystatin C equations. The combined BTP-B2M equation (BTP and B2M alone) had similar accuracy to the CKD-EPI creatinine or cystatin C equation. The average of the BTP-B2M equation and the CKD-EPI creatinine-cystatin C equation was not more accurate than the CKD-EPI creatinine-cystatin C equation. Limitations No external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race. Conclusions BTP and B2M are less influenced by age, sex, and race than creatinine and less influenced by race than cystatin C, but provide less accurate GFR estimates than the CKD-EPI creatinine and cystatin C equations. The CKD-EPI BTP and B2M equation provides a methodological advance for their study as filtration markers and in their associations with risk and adverse outcomes, but further study is required before clinical use.",
keywords = "beta-2-microglobulin (B2M), Beta-trace protein (BTP), chronic kidney disease (CKD), diagnostic accuracy, estimated glomerular filtration rate (eGFR), estimating equation, filtration marker, kidney function, measured GFR",
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T1 - GFR Estimation Using β-Trace Protein and β2-Microglobulin in CKD

AU - Inker, Lesley A.

AU - Tighiouart, Hocine

AU - Coresh, Josef

AU - Foster, Meredith C.

AU - Anderson, Amanda H.

AU - Beck, Gerald J.

AU - Contreras, Gabriel

AU - Greene, Tom

AU - Karger, Amy B.

AU - Kusek, John W.

AU - Lash, James

AU - Lewis, Julia

AU - Schelling, Jeffrey R.

AU - Navaneethan, Sankar D.

AU - Sondheimer, James

AU - Shafi, Tariq

AU - Levey, Andrew S.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background β-Trace protein (BTP) and β2-microglobulin (B2M) are novel glomerular filtration markers that have stronger associations with adverse outcomes than creatinine. Comparisons of BTP and B2M to creatinine and cystatin C are limited by the absence of rigorously developed glomerular filtration rate (GFR) estimating equations for the novel markers. Study Design Study of diagnostic test accuracy. Setting & Participants Pooled database of 3 populations with chronic kidney disease (CKD) with mean measured GFR of 48 mL/min/1.73 m2 (N = 3,551; MDRD [Modification of Diet in Renal Disease] Study, AASK [African American Study of Kidney Disease and Hypertension], and CRIC [Chronic Renal Insufficiency Cohort] Study). Index Tests GFR estimated using creatinine, cystatin C, BTP, or B2M level. Reference Test GFR measured as the urinary clearance of iothalamate. Results For BTP and B2M, coefficients for age, sex, and race were smaller than for creatinine and were similar or smaller than for cystatin C. For B2M, coefficients for sex, age, and race were smaller than for creatinine and were similar (age and race) or smaller (sex) than for cystatin C. The final equations with BTP (BTP, age, and sex) or B2M (B2M alone) were less accurate than either the CKD-EPI (CKD Epidemiology Collaboration) creatinine or cystatin C equations. The combined BTP-B2M equation (BTP and B2M alone) had similar accuracy to the CKD-EPI creatinine or cystatin C equation. The average of the BTP-B2M equation and the CKD-EPI creatinine-cystatin C equation was not more accurate than the CKD-EPI creatinine-cystatin C equation. Limitations No external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race. Conclusions BTP and B2M are less influenced by age, sex, and race than creatinine and less influenced by race than cystatin C, but provide less accurate GFR estimates than the CKD-EPI creatinine and cystatin C equations. The CKD-EPI BTP and B2M equation provides a methodological advance for their study as filtration markers and in their associations with risk and adverse outcomes, but further study is required before clinical use.

AB - Background β-Trace protein (BTP) and β2-microglobulin (B2M) are novel glomerular filtration markers that have stronger associations with adverse outcomes than creatinine. Comparisons of BTP and B2M to creatinine and cystatin C are limited by the absence of rigorously developed glomerular filtration rate (GFR) estimating equations for the novel markers. Study Design Study of diagnostic test accuracy. Setting & Participants Pooled database of 3 populations with chronic kidney disease (CKD) with mean measured GFR of 48 mL/min/1.73 m2 (N = 3,551; MDRD [Modification of Diet in Renal Disease] Study, AASK [African American Study of Kidney Disease and Hypertension], and CRIC [Chronic Renal Insufficiency Cohort] Study). Index Tests GFR estimated using creatinine, cystatin C, BTP, or B2M level. Reference Test GFR measured as the urinary clearance of iothalamate. Results For BTP and B2M, coefficients for age, sex, and race were smaller than for creatinine and were similar or smaller than for cystatin C. For B2M, coefficients for sex, age, and race were smaller than for creatinine and were similar (age and race) or smaller (sex) than for cystatin C. The final equations with BTP (BTP, age, and sex) or B2M (B2M alone) were less accurate than either the CKD-EPI (CKD Epidemiology Collaboration) creatinine or cystatin C equations. The combined BTP-B2M equation (BTP and B2M alone) had similar accuracy to the CKD-EPI creatinine or cystatin C equation. The average of the BTP-B2M equation and the CKD-EPI creatinine-cystatin C equation was not more accurate than the CKD-EPI creatinine-cystatin C equation. Limitations No external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race. Conclusions BTP and B2M are less influenced by age, sex, and race than creatinine and less influenced by race than cystatin C, but provide less accurate GFR estimates than the CKD-EPI creatinine and cystatin C equations. The CKD-EPI BTP and B2M equation provides a methodological advance for their study as filtration markers and in their associations with risk and adverse outcomes, but further study is required before clinical use.

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KW - Beta-trace protein (BTP)

KW - chronic kidney disease (CKD)

KW - diagnostic accuracy

KW - estimated glomerular filtration rate (eGFR)

KW - estimating equation

KW - filtration marker

KW - kidney function

KW - measured GFR

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