TY - JOUR
T1 - 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
AU - on behalf of the CKD Biomarker Consortium and the CRIC Study Investigators
AU - Foster, Meredith C.
AU - Coresh, Josef
AU - Hsu, Chi Yuan
AU - Xie, Dawei
AU - Levey, Andrew S.
AU - Nelson, Robert G.
AU - Eckfeldt, John H.
AU - Vasan, Ramachandran S.
AU - Kimmel, Paul L.
AU - Schelling, Jeffrey
AU - Simonson, Michael
AU - Sondheimer, James H.
AU - Anderson, Amanda Hyre
AU - Akkina, Sanjeev
AU - Feldman, Harold I.
AU - Kusek, John W.
AU - Ojo, Akinlolu O.
AU - Inker, Lesley A.
AU - Appel, Lawrence J.
AU - Go, Alan S.
AU - He, Jiang
AU - Lash, James P.
AU - Rahman, Mahboob
AU - Townsend, Raymond R.
N1 - Funding Information:
Support: The CKD Biomarkers Consortium is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; U01DK85649 , U01DK085673 , U01DK085660 , U01DK085688 , U01DK085651 , and U01DK085689 ) and the Intramural Research Program of the NIDDK. Dr Foster was supported in part by National Heart, Lung and Blood Institute grant T32 HL007024 . Funding for the CRIC Study was obtained under a cooperative agreement from the NIDDK ( U01DK060990 , U01DK060984 , U01DK061022 , U01DK061021 , U01DK061028 , U01DK060980 , U01DK060963 , and U01DK060902 ). In addition, this work was supported in part by the following: the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award (CTSA) National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) UL1TR000003 , Johns Hopkins University UL1 TR-000424 , University of Maryland GCRC M01 RR-16500 , Clinical and Translational Science Collaborative of Cleveland , UL1TR000439 from the NCATS component of the NIH and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research UL1TR000433 , University of Illinois at Chicago CTSA UL1RR029879 , Tulane University Translational Research in Hypertension and Renal Biology P30GM103337 , and Kaiser Permanente NIH/National Center for Research Resources University of California San Francisco−Clinical and Translational Science Institute UL1 RR-024131 . Institutional review board approval numbers for the CRIC Study include University of Pennsylvania ( 707819 and 807882 ), Johns Hopkins University ( NA_00044034 ), University of Maryland ( HCR-HP-00041233-6 ), University Hospitals of Cleveland ( 02-03-04 ), MetroHealth Medical Center ( IRB03-00052 ), Cleveland Clinic Foundation ( 5969 ), University of Michigan ( HUM00073515 ), St. John Health System ( SJ 0403-04 ), Wayne State University ( 071803MP2F ), University of Illinois ( 2003-0149 ), Tulane University ( H0340 ), and Kaiser Permanente/UCSF ( CN-01AGo-02-H ). The funders of this study did not have a role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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. Study Design: Prospective cohort study. Setting & Participants: 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). Predictors 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. Outcomes: 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. Limitations: 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.
AB - 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. Study Design: Prospective cohort study. Setting & Participants: 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). Predictors 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. Outcomes: 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. Limitations: 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.
KW - Beta-trace protein (BTP)
KW - CKD Biomarkers Consortium
KW - Chronic Renal Insufficiency Cohort (CRIC)
KW - cardiovascular events
KW - chronic kidney disease (CKD)
KW - end-stage renal disease (ESRD)
KW - estimated glomerular filtration rate (EGFR)
KW - filtration markers
KW - mortality
KW - renal function
KW - β-microglobulin (B2M)
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U2 - 10.1053/j.ajkd.2016.01.015
DO - 10.1053/j.ajkd.2016.01.015
M3 - Article
C2 - 26948990
AN - SCOPUS:84959278151
VL - 68
SP - 68
EP - 76
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
SN - 0272-6386
IS - 1
ER -