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

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 (eGFR_cr), 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 eGFR_cr (P vs eGFR_cr ≤ 0.02). The 4-marker composite score led to improvements in C statistic and 2.5-year risk reclassification beyond eGFR_cr 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 eGFR_cr, and the use of multiple markers may improve risk prediction beyond this well-established marker of kidney function among persons with moderate CKD.