Novel Filtration Markers as Predictors of All-Cause and Cardiovascular Mortality in US Adults

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.

http://www.ajkd.org/article/S0272-6386(13)00107-8/abstract