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

• DOI: 10.1053/j.ajkd.2016.01.015
• Publication Date: 2016-03-03T13:29:26Z
• Authors: Meredith C. Foster; Josef Coresh; Chi-yuan Hsu; Dawei Xie; Andrew S. Levey; Robert G. Nelson; John H. Eckfeldt; Ramachandran S. V...; Paul L. Kimmel; Jeffrey Schelling; Michael Simonson; James H. Sondheimer; Amanda Hyre Anderson; Sanjeev Akkina; Harold I. Feldman; John W. Kusek; Akinlolu O. Ojo; Lesley A. Inker; Lawrence J. Appel; Alan S. Go; Jiang He; James P. Lash; Mahboob Rahman; Raymond R. Townsend
• Keywords: Male; Kidney Disease; estimated glomerular filtration rate; Clinical Sciences; Renal and urogenital; CKD Biomarkers Consortium; Clinical sciences; Cardiovascular; Kidney Failure; Cohort Studies; cardiovascular events; β(2)-microglobulin; 03 medical and health sciences; 0302 clinical medicine; Clinical Research; Predictive Value of Tests; Humans; beta(2)-microglobulin; Renal Insufficiency; Prospective Studies; Chronic; Renal Insufficiency, Chronic; CKD Biomarker Consortium and the CRIC Study Investigators; end-stage renal disease; Biomedical and Clinical Sciences; Beta-trace protein; Prevention; renal function; Urology & Nephrology; Middle Aged; filtration markers; mortality; Lipocalins; 3. Good health; Intramolecular Oxidoreductases; Good Health and Well Being; Cardiovascular Diseases; Public Health and Health Services; Kidney Failure, Chronic; Female; Chronic Renal Insufficiency Cohort; beta 2-Microglobulin; chronic kidney disease; Biomarkers

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.Prospective cohort study.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).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.ESRD, all-cause mortality, and new-onset cardiovascular disease.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.Filtration markers measured at one time point; measured GFR available in subset of cohort.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.