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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.
Am J Kidney Dis 2016; 68(1):68-76AJ

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.

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.

Authors+Show Affiliations

Tufts Medical Center, Boston, MA.Johns Hopkins University, Baltimore, MD.University of California, San Francisco, San Francisco, CA.University of Pennsylvania, Philadelphia, PA.Tufts Medical Center, Boston, MA.National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ.University of Minnesota, Minneapolis, MN.Boston University, Boston, MA.National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.MetroHealth Medical Center, Cleveland, OH.Case Western Reserve University, Cleveland, OH.Wayne State University School of Medicine, Detroit, MI.University of Pennsylvania, Philadelphia, PA.University of Illinois, Chicago, IL.University of Pennsylvania, Philadelphia, PA.National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.University of Michigan School of Medicine, Ann Arbor, MI.Tufts Medical Center, Boston, MA. Electronic address: linker@tuftsmedicalcenter.org.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Observational Study

Language

eng

PubMed ID

26948990

Citation

Foster, Meredith C., et al. "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." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 68, no. 1, 2016, pp. 68-76.
Foster MC, Coresh J, Hsu CY, et al. 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. Am J Kidney Dis. 2016;68(1):68-76.
Foster, M. C., Coresh, J., Hsu, C. Y., Xie, D., Levey, A. S., Nelson, R. G., ... Inker, L. A. (2016). 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. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 68(1), pp. 68-76. doi:10.1053/j.ajkd.2016.01.015.
Foster MC, et al. 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. Am J Kidney Dis. 2016;68(1):68-76. PubMed PMID: 26948990.
* Article titles in AMA citation format should be in sentence-case
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 - 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 - ,, Y1 - 2016/03/03/ PY - 2015/08/27/received PY - 2016/01/05/accepted PY - 2016/3/8/entrez PY - 2016/3/8/pubmed PY - 2017/6/1/medline 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(2)-microglobulin (B2M) SP - 68 EP - 76 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am. J. Kidney Dis. VL - 68 IS - 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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/26948990/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(16)00131-1 DB - PRIME DP - Unbound Medicine ER -