title: Filtration markers as predictors of ESRD and mortality in Southwestern American Indians with type 2 diabetes.
abstract: BACKGROUND
  A growing number of serum filtration markers are associated with mortality and end-stage renal disease (ESRD) in adults. Whether β-trace protein (BTP) and β2-microglobulin (B2M) are associated with these outcomes in adults with type 2 diabetes is not known.
  
  
  METHODS
  Longitudinal cohort study.
  
  
  METHODS
  250 Pima Indians with type 2 diabetes (69% women; mean age, 42 years; mean diabetes duration, 11 years).
  
  
  METHODS
  Serum BTP, B2M, and glomerular filtration rate measured by iothalamate clearance (mGFR) or estimated using creatinine (eGFRcr) or cystatin C level (eGFRcys).
  
  
  METHODS
  Incident ESRD and all-cause mortality through December 2013. HRs were reported per interquartile range decrease of the inverse of BTP and B2M (1/BTP and 1/B2M) using Cox regression. Improvement in risk prediction with the addition of BTP or B2M level to established markers (eGFRcys with mGFR or eGFRcr) was evaluated using C statistics, continuous net reclassification improvement, and relative integrated discrimination improvement (RIDI).
  
  
  RESULTS
  During a median follow-up of 14 years, 69 participants developed ESRD and 95 died. Both novel markers were associated with ESRD in multivariable models. BTP level remained statistically significant after further adjustment for mGFR (1/BTP, 1.53 [95% CI, 1.01-2.30]; 1/B2M, 1.54 [95% CI, 0.98-2.42]). B2M level was associated with mortality in multivariable models and after further adjustment for mGFR (HR, 2.12; 95% CI, 1.38-3.26). The addition of B2M level to established markers increased the C statistic for mortality but only weakly when assessed by either continuous net reclassification improvement or RIDI; none was improved for ESRD by the addition of these markers.
  
  
  CONCLUSIONS
  Small sample size, single measurements of markers.
  
  
  CONCLUSIONS
  In Pima Indians with type 2 diabetes, BTP and, to a lesser extent, B2M levels were associated with ESRD. B2M level was associated with mortality after adjustment for traditional risk factors and established filtration markers. Further studies are warranted to confirm whether inclusion of B2M level in a multimarker approach leads to improved risk prediction for mortality in this population.
authors.affiliation: Tufts Medical Center, Boston, MA.
authors.forename: Meredith C
authors.initials: MC
authors.lastname: Foster
authors.affiliation: Tufts Medical Center, Boston, MA.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Inker
authors.affiliation: University of California, San Francisco, San Francisco, CA.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: University of Minnesota, Minneapolis, MN.
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
authors.affiliation: Tufts Medical Center, Boston, MA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA.
authors.forename: Meda E
authors.initials: ME
authors.lastname: Pavkov
authors.affiliation: Stanford University, Stanford, CA.
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Myers
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Bennett
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: Boston University, Boston, MA.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ. Electronic address: rnelson@nih.gov.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nelson
mesh_terms: D000328:Adult; D001130:Arizona / Q000453:epidemiology; D015415:Biomarkers; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology* / Q000401:mortality / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000208:ethnology* / Q000401:mortality / Q000503:physiopathology; D018450:Disease Progression; D004198:Disease Susceptibility; D005006:Ethnicity; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D006949:Hyperlipidemias / Q000208:ethnology; D006973:Hypertension / Q000208:ethnology; D007198:Indians, North American; D019746:Intramolecular Oxidoreductases / Q000097:blood*; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood / Q000208:ethnology* / Q000401:mortality / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000503:physiopathology*; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D001613:beta 2-Microglobulin / Q000032:analysis*
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; Pima Indians; beta-2 microglobulin (B2M); diabetic kidney failure; end-stage renal disease (ESRD); filtration markers; glomerular filtration rate (GFR); kidney function; mortality; type 2 diabetes mellitus