title: Filtration Markers as Predictors of ESRD and Mortality: Individual Participant Data Meta-Analysis.
abstract: Serum β-trace protein (BTP) and β-2 microglobulin (B2M) are associated with risk of ESRD and death in the general population and in populations at high risk for these outcomes (GP/HR) and those with CKD, but results differ among studies.
  
  
  
  We performed an individual patient-level meta-analysis including three GP/HR studies (n=17,903 participants) and three CKD studies (n=5415). We compared associations, risk prediction, and improvement in reclassification of eGFR using BTP (eGFRBTP) and B2M (eGFRB2M) alone and the average (eGFRavg) of eGFRBTP, eGFRB2M, creatinine (eGFRcr), and cystatin C (eGFRcys), to eGFRcr, eGFRcys, and their combination (eGFRcr-cys) for ESRD (2075 events) and death (7275 events).
  
  
  
  Mean (SD) follow up times for ESRD and mortality for GP/HR and CKD studies were 13 (4), 6.2 (3.2), 14 (5), and 7.5 (3.9) years, respectively. Compared with eGFRcr, eGFRBTPand eGFRB2Mimproved risk associations and modestly improved prediction for ESRD and death even after adjustment for established risk factors. eGFRavgprovided the most consistent improvement in associations and prediction across both outcomes and populations. Assessment of heterogeneity did not yield clinically relevant differences. For ESRD, addition of albuminuria substantially attenuated the improvement in risk prediction and risk classification with novel filtration markers. For mortality, addition of albuminuria did not affect the improvement in risk prediction with the use of novel markers, but lessened improvement in risk classification, especially for the CKD cohort.
  
  
  
  These markers do not provide substantial additional prognostic information to eGFRcrand albuminuria, but may be appropriate in circumstances where eGFRcris not accurate or albuminuria is not available. Educational efforts to increase measurement of albuminuria in clinical practice may be more cost-effective than measurement of BTP and B2M for improving prognostic information.
authors.affiliation: William B. Schwartz Division of Nephrology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Inker
authors.affiliation: Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.affiliation: Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Sang
authors.affiliation: Department of Medicine, University of California-San Francisco, San Francisco, California.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: William B. Schwartz Division of Nephrology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Meredith C
authors.initials: MC
authors.lastname: Foster
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Karger
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nelson
authors.affiliation: William B. Schwartz Division of Nephrology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.affiliation: William B. Schwartz Division of Nephrology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Mark
authors.initials: M
authors.lastname: Sarnak
authors.affiliation: Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Appel
authors.affiliation: Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Morgan
authors.initials: M
authors.lastname: Grams
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Dawei
authors.initials: D
authors.lastname: Xie
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; and.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kimmel
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Harold
authors.initials: H
authors.lastname: Feldman
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Vasan
authors.initials: V
authors.lastname: Ramachandran
authors.affiliation: William B. Schwartz Division of Nephrology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000453:epidemiology* / Q000503:physiopathology; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D001613:beta 2-Microglobulin / Q000097:blood*
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D054834:Lipocalins; D001613:beta 2-Microglobulin; D003404:Creatinine; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase
keywords: albuminuria; beta 2-microglobulin; chronic kidney disease; follow-up studies; glomerular filtration rate; humans; intramolecular oxidoreductases; kidney failure, chronic; lipocalins; prostaglandin R2 D-isomerase; renal insufficiency, chronic; risk factors