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

doi:10.1053/j.ajkd.2015.07.025

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

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

114 Scopus citations

Abstract

Background: β-Trace protein (BTP) and β<inf>2</inf>-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 48mL/min/1.73m<sup>2</sup> (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 language	English (US)
Pages (from-to)	40-48
Number of pages	9
Journal	American journal of kidney diseases : the official journal of the National Kidney Foundation
Volume	67
Issue number	1
DOIs	https://doi.org/10.1053/j.ajkd.2015.07.025
State	Published - Jan 1 2016

Bibliographical note

Funding Information:
Support: This work is supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK097020 ; NIDDK U01 DK085689 (Chronic Kidney Disease Biomarkers Consortium; Drs Coresh, Levey, and Inker); NIDDK U01 DK045388 and the NCMHHD M01 RR00071 (AASK); NIDDK U01 DK35073 (MDRD Study); and cooperative agreements from NIDDK (U01 DK060990, U01 DK060984, U01 DK061022, U01 DK061021, U01 DK061028, U01 DK060980, U01 DK060963, and U01 DK060902); and is supported in part by the following institutional Clinical Translational Science Awards (CTSA) and other NIH grants: University of Pennsylvania NIH/National Center for Advancing Translational Sciences (NCATS) UL1 TR000003 , K01 DK092353 , and K24 DK002651 , Johns Hopkins University UL1 TR000424, University of Maryland General Clinical Research Center M01 RR16500 , Clinical and Translational Science Collaborative of Cleveland , UL1 TR000439 from the NCATS component of the NIH and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research UL1 TR000433 , University of Illinois at Chicago CTSA UL1 RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30 GM103337 , Kaiser Permanente NIH/National Center for Research Resources University of California San Francisco-Clinical and Translational Science Institute UL1 RR024131 (CRIC Study). Dr Shafi is supported by NIDDK grant K23 DK083514.

Publisher Copyright:
© 2016 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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

PubMed: MeSH publication types

Clinical Study
Journal Article
Research Support, N.I.H., Extramural

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1053/j.ajkd.2015.07.025

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Cite this

Inker, L. A., Tighiouart, H., Coresh, J., Foster, M. C., Anderson, A. H., Beck, G. J., Contreras, G., Greene, T., Karger, A. B., Kusek, J. W., Lash, J., Lewis, J., Schelling, J. R., Navaneethan, S. D., Sondheimer, J., Shafi, T., & Levey, A. S. (2016). GFR Estimation Using β-Trace Protein and β₂-Microglobulin in CKD. American journal of kidney diseases : the official journal of the National Kidney Foundation, 67(1), 40-48. https://doi.org/10.1053/j.ajkd.2015.07.025

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 : the official journal of the National Kidney Foundation, vol. 67, no. 1, pp. 40-48. https://doi.org/10.1053/j.ajkd.2015.07.025

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title = "GFR Estimation Using β-Trace Protein and β2-Microglobulin in CKD",

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 48mL/min/1.73m2 (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",

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

note = "Funding Information: Support: This work is supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK097020 ; NIDDK U01 DK085689 (Chronic Kidney Disease Biomarkers Consortium; Drs Coresh, Levey, and Inker); NIDDK U01 DK045388 and the NCMHHD M01 RR00071 (AASK); NIDDK U01 DK35073 (MDRD Study); and cooperative agreements from NIDDK (U01 DK060990, U01 DK060984, U01 DK061022, U01 DK061021, U01 DK061028, U01 DK060980, U01 DK060963, and U01 DK060902); and is supported in part by the following institutional Clinical Translational Science Awards (CTSA) and other NIH grants: University of Pennsylvania NIH/National Center for Advancing Translational Sciences (NCATS) UL1 TR000003 , K01 DK092353 , and K24 DK002651 , Johns Hopkins University UL1 TR000424, University of Maryland General Clinical Research Center M01 RR16500 , Clinical and Translational Science Collaborative of Cleveland , UL1 TR000439 from the NCATS component of the NIH and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research UL1 TR000433 , University of Illinois at Chicago CTSA UL1 RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30 GM103337 , Kaiser Permanente NIH/National Center for Research Resources University of California San Francisco-Clinical and Translational Science Institute UL1 RR024131 (CRIC Study). Dr Shafi is supported by NIDDK grant K23 DK083514. Publisher Copyright: {\textcopyright} 2016 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.",

year = "2016",

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doi = "10.1053/j.ajkd.2015.07.025",

language = "English (US)",

volume = "67",

pages = "40--48",

journal = "American journal of kidney diseases : the official journal of the National Kidney Foundation",

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TY - JOUR

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.

N1 - Funding Information: Support: This work is supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK097020 ; NIDDK U01 DK085689 (Chronic Kidney Disease Biomarkers Consortium; Drs Coresh, Levey, and Inker); NIDDK U01 DK045388 and the NCMHHD M01 RR00071 (AASK); NIDDK U01 DK35073 (MDRD Study); and cooperative agreements from NIDDK (U01 DK060990, U01 DK060984, U01 DK061022, U01 DK061021, U01 DK061028, U01 DK060980, U01 DK060963, and U01 DK060902); and is supported in part by the following institutional Clinical Translational Science Awards (CTSA) and other NIH grants: University of Pennsylvania NIH/National Center for Advancing Translational Sciences (NCATS) UL1 TR000003 , K01 DK092353 , and K24 DK002651 , Johns Hopkins University UL1 TR000424, University of Maryland General Clinical Research Center M01 RR16500 , Clinical and Translational Science Collaborative of Cleveland , UL1 TR000439 from the NCATS component of the NIH and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research UL1 TR000433 , University of Illinois at Chicago CTSA UL1 RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30 GM103337 , Kaiser Permanente NIH/National Center for Research Resources University of California San Francisco-Clinical and Translational Science Institute UL1 RR024131 (CRIC Study). Dr Shafi is supported by NIDDK grant K23 DK083514. Publisher Copyright: © 2016 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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 48mL/min/1.73m2 (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 48mL/min/1.73m2 (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.

KW - Beta-2-microglobulin (B2M)

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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