Background: New filtration markers, including β-trace protein (BTP) and β2-microglobulin (B2M), may, similar to cystatin C, enable a stronger prediction of mortality compared to serum creatinine-based estimated glomerular filtration rate (eGFRcr). We sought to evaluate these mortality associations in a representative sample of US adults. Study Design: Prospective cohort study. Setting & Participants: 6,445 adults 20 years or older from the Third National Health and Nutrition Examination Survey (1988-1994) with mortality linkage through December 31, 2006. Predictors: Serum cystatin C, BTP, and B2M levels and eGFRcr categorized into quintiles, with the highest quintile (lowest for eGFRcr) split into tertiles (subquintiles Q5a-Q5c). Outcomes: All-cause, cardiovascular disease, and coronary heart disease mortality. Measurements: Demographic- and multivariable-adjusted Cox proportional hazard models. Results: During follow-up, 2,392 deaths (cardiovascular, 1,079; coronary heart disease, 605) occurred. Levels of all 4 filtration markers were associated with mortality risk after adjusting for demographics (P trend < 0.02). Adjusted for mortality risk factors, compared to the middle quintile, the highest subquintiles for cystatin C (Q5c: HR, 1.94; 95% CI, 1.43-2.62), BTP (Q5c: HR, 2.14; 95% CI, 1.56-2.94), and B2M (Q5c: HR, 2.58; 95% CI, 1.96-3.41) were associated with increased all-cause mortality risk, whereas the association was weaker for eGFRcr (Q5c: HR, 1.31; 95% CI, 0.84-2.04). Associations persisted for the novel markers and not for eGFRcr at eGFRcr ≥60 mL/min/1.73 m2. Trends were similar for cardiovascular disease and coronary heart disease mortality. Limitations: Single measurements of markers from long-term stored samples. Conclusions: The strong association of cystatin C level with mortality compared with serum creatinine estimates is shared by BTP and B2M. This supports the utility of alternative filtration markers beyond creatinine when improved risk prediction related to decreased GFR is needed.
Bibliographical noteFunding Information:
Support: The study was partially supported by National Institutes of Health (NIH) grants 5U01DK067651 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]; Drs Inker, Levey, Selvin, Eckfeldt, and Coresh) and 1U01DK085689 (CKD Biomarkers Consortium; Drs Foster, Inker, Levey, Eckfeldt, and Coresh). Dr Foster and Mr Juraschek are supported in part by NIH/National Heart, Lung and Blood Institute Cardiovascular Epidemiology training grant T32HL007024 . Siemens Healthcare Diagnostics provided a grant to the University of Minnesota for labor and reagents to conduct the B2M and BTP and some cystatin C assays.
- Cystatin C
- Third National Health and Nutrition Examination Survey
- estimated glomerular filtration rate
- β-trace protein