• 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, and Andrew S Levey.
• Tufts Medical Center, Boston, MA. Electronic address: linker@tuftsmedicalcenter.org.
• Am. J. Kidney Dis. 2016 Jan 1; 67 (1): 40-8.

Backgroundβ-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 DesignStudy of diagnostic test accuracy.Setting & ParticipantsPooled 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 TestsGFR estimated using creatinine, cystatin C, BTP, or B2M level.Reference TestGFR measured as the urinary clearance of iothalamate.ResultsFor 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.LimitationsNo external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race.ConclusionsBTP 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.Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

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