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

• Published in: American journal of kidney diseases Vol. 68; no. 1; pp. 68 - 76
• Main Authors: Foster, Meredith C., ScD, MPH, Coresh, Josef, MD, PhD, Hsu, Chi-yuan, MD, MSc, Xie, Dawei, PhD, Levey, Andrew S., MD, Nelson, Robert G., MD, PhD, Eckfeldt, John H., MD, PhD, Vasan, Ramachandran S., MD, Kimmel, Paul L., MD, Schelling, Jeffrey, MD, Simonson, Michael, PhD, Sondheimer, James H., MD, Anderson, Amanda Hyre, PhD, MPH, Akkina, Sanjeev, MD, Feldman, Harold I., MD, Kusek, John W., PhD, Ojo, Akinlolu O., MD, PhD, Inker, Lesley A., MD, MS
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2016
• Subjects: beta 2-Microglobulin - blood; Beta-trace protein (BTP); Biomarkers; Cardiovascular Diseases - etiology; cardiovascular events; chronic kidney disease (CKD); Chronic Renal Insufficiency Cohort (CRIC); CKD Biomarkers Consortium; Cohort Studies; end-stage renal disease (ESRD); estimated glomerular filtration rate (eGFR); Female; filtration markers; Humans; Intramolecular Oxidoreductases - blood; Kidney Failure, Chronic - etiology; Lipocalins - blood; Male; Middle Aged; mortality; Nephrology; Predictive Value of Tests; Prospective Studies; renal function; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - mortality; β2-microglobulin (B2M); cardiovascular events; Chronic Renal Insufficiency Cohort (CRIC); CKD Biomarkers Consortium; filtration markers; end-stage renal disease (ESRD); Beta-trace protein (BTP); estimated glomerular filtration rate (eGFR); mortality; renal function; β 2-microglobulin (B2M); chronic kidney disease (CKD); β2-microglobulin (B2M); β-microglobulin (B2M)
• ISSN: 0272-6386; 1523-6838
• DOI: 10.1053/j.ajkd.2016.01.015

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.