Lesley A Inker1, Hocine Tighiouart2, Josef Coresh3, Meredith C Foster4, Amanda H Anderson5, Gerald J Beck6, Gabriel Contreras7, Tom Greene8, Amy B Karger9, John W Kusek10, James Lash11, Julia Lewis12, Jeffrey R Schelling13, Sankar D Navaneethan6, James Sondheimer14, Tariq Shafi3, Andrew S Levey4. 1. Tufts Medical Center, Boston, MA. Electronic address: linker@tuftsmedicalcenter.org. 2. Tufts Medical Center, Boston, MA; Research Design Center/Biostatistics Research Center, Tufts CTSI and Institute for Clinical Research and Health Policy Studies, Boston, MA. 3. Johns Hopkins University School of Medicine, Baltimore, MD. 4. Tufts Medical Center, Boston, MA. 5. Perelman School of Medicine at the University of Pennsylvania. Philadelphia, PA. 6. Cleveland Clinic, Cleveland, OH. 7. University of Miami Miller School of Medicine, Miami, FL. 8. University of Utah, Salt Lake City, UT. 9. University of Minnesota, Minneapolis, MN. 10. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD. 11. University of Illinois at Chicago, Chicago, IL. 12. Vanderbilt Medical Center, Nashville, TN. 13. Case Western Reserve University, MetroHealth Medical Center, Cleveland, OH. 14. Wayne State University, Detroit, MI.
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.
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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