Meredith C Foster1, Josef Coresh2, Chi-Yuan Hsu3, Dawei Xie4, Andrew S Levey1, Robert G Nelson5, John H Eckfeldt6, Ramachandran S Vasan7, Paul L Kimmel8, Jeffrey Schelling9, Michael Simonson10, James H Sondheimer11, Amanda Hyre Anderson4, Sanjeev Akkina12, Harold I Feldman4, John W Kusek8, Akinlolu O Ojo13, Lesley A Inker14. 1. Tufts Medical Center, Boston, MA. 2. Johns Hopkins University, Baltimore, MD. 3. University of California, San Francisco, San Francisco, CA. 4. University of Pennsylvania, Philadelphia, PA. 5. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ. 6. University of Minnesota, Minneapolis, MN. 7. Boston University, Boston, MA. 8. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. 9. MetroHealth Medical Center, Cleveland, OH. 10. Case Western Reserve University, Cleveland, OH. 11. Wayne State University School of Medicine, Detroit, MI. 12. University of Illinois, Chicago, IL. 13. University of Michigan School of Medicine, Ann Arbor, MI. 14. Tufts Medical Center, Boston, MA. Electronic address: linker@tuftsmedicalcenter.org.
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.
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.
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