title: Serum β-Trace Protein and β2-Microglobulin as Predictors of ESRD, Mortality, and Cardiovascular Disease in Adults With CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study.
abstract: BACKGROUND
  Serum β-trace protein (BTP) and β2-microglobulin (B2M) are independently associated with end-stage renal disease (ESRD) and mortality in the general population and high-risk groups with diabetes or advanced chronic kidney disease (CKD). Less is known about their associations with outcomes and predictive ability in adults with moderate CKD.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  3,613 adults from the CRIC (Chronic Renal Insufficiency Cohort) Study (45% women; mean age, 57.9 years; 41.0% non-Hispanic black; 51.9% with diabetes).
  
  
  METHODS
  BTP and B2M levels with a reciprocal transformation to reflect their associations with filtration, creatinine-based estimated glomerular filtration rate (eGFRcr), measured GFR, and a 4-marker composite score combining BTP, B2M, creatinine, and cystatin C levels. Predictors were standardized as z scores for comparisons across filtration markers.
  
  
  RESULTS
  ESRD, all-cause mortality, and new-onset cardiovascular disease.
  
  
  RESULTS
  During a 6-year median follow-up, 755 (21%) participants developed ESRD, 653 died, and 292 developed new-onset cardiovascular disease. BTP, B2M, and the 4-marker composite score were independent predictors of ESRD and all-cause mortality, and B2M and the 4-marker composite score of cardiovascular events, after multivariable adjustment. These associations were stronger than those observed for eGFRcr (P vs eGFRcr≤0.02). The 4-marker composite score led to improvements in C statistic and 2.5-year risk reclassification beyond eGFRcr for all outcomes.
  
  
  CONCLUSIONS
  Filtration markers measured at one time point; measured GFR available in subset of cohort.
  
  
  CONCLUSIONS
  BTP and B2M levels may contribute additional risk information beyond eGFRcr, and the use of multiple markers may improve risk prediction beyond this well-established marker of kidney function among persons with moderate CKD.
authors.affiliation: Tufts Medical Center, Boston, MA.
authors.forename: Meredith C
authors.initials: MC
authors.lastname: Foster
authors.affiliation: Johns Hopkins University, Baltimore, MD.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.affiliation: University of California, San Francisco, San Francisco, CA.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: University of Pennsylvania, Philadelphia, PA.
authors.forename: Dawei
authors.initials: D
authors.lastname: Xie
authors.affiliation: Tufts Medical Center, Boston, MA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nelson
authors.affiliation: University of Minnesota, Minneapolis, MN.
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
authors.affiliation: Boston University, Boston, MA.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kimmel
authors.affiliation: MetroHealth Medical Center, Cleveland, OH.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schelling
authors.affiliation: Case Western Reserve University, Cleveland, OH.
authors.forename: Michael
authors.initials: M
authors.lastname: Simonson
authors.affiliation: Wayne State University School of Medicine, Detroit, MI.
authors.forename: James H
authors.initials: JH
authors.lastname: Sondheimer
authors.affiliation: University of Pennsylvania, Philadelphia, PA.
authors.forename: Amanda Hyre
authors.initials: AH
authors.lastname: Anderson
authors.affiliation: University of Illinois, Chicago, IL.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Akkina
authors.affiliation: University of Pennsylvania, Philadelphia, PA.
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
authors.forename: John W
authors.initials: JW
authors.lastname: Kusek
authors.affiliation: University of Michigan School of Medicine, Ann Arbor, MI.
authors.forename: Akinlolu O
authors.initials: AO
authors.lastname: Ojo
authors.affiliation: Tufts Medical Center, Boston, MA. Electronic address: linker@tuftsmedicalcenter.org.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Inker
mesh_terms: D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000209:etiology; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000401:mortality*; D001613:beta 2-Microglobulin / Q000097:blood*
chemical_list: D015415:Biomarkers; D054834:Lipocalins; D001613:beta 2-Microglobulin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase
keywords: Beta-trace protein (BTP); CKD Biomarkers Consortium; Chronic Renal Insufficiency Cohort (CRIC); cardiovascular events; chronic kidney disease (CKD); end-stage renal disease (ESRD); estimated glomerular filtration rate (eGFR); filtration markers; mortality; renal function; β(2)-microglobulin (B2M)