Novel markers of kidney function as predictors of ESRD, cardiovascular disease, and mortality in the general population

Abstract

Background: Cystatin C level predicts mortality more strongly than serum creatinine level. It is unknown whether this advantage extends to other outcomes, such as kidney failure, or whether other novel renal filtration markers share this advantage in predicting outcomes.

Study design: Observational cohort study.

Setting & participants: 9,988 participants in the Atherosclerosis Risk in Communities (ARIC) Study, a population-based study in 4 US communities, followed for approximately 10 years.

Predictors: Serum creatinine-based estimated glomerular filtration rate calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (eGFR(CKD-EPI)) and cystatin C, β-trace protein (BTP), and β(2)-microglobulin (B2M) levels.

Outcomes: Mortality, coronary heart disease, heart failure, and kidney failure.

Results: Higher cystatin C and B2M concentrations were associated more strongly with mortality (n = 1,425) than BTP level and all were associated more strongly than eGFR(CKD-EPI) (adjusted HR for the upper 6.7 percentile compared with the lowest quintile: 1.6 [95% CI, 1.3-1.9] for eGFR(CKD-EPI), 2.9 [95% CI, 2.3-3.6] for cystatin C level, 1.9 [95% CI, 1.5-2.4] for BTP level, and 3.0 [95% CI, 2.4-3.8] for B2M level). Similar patterns were observed for coronary heart disease (n = 1,279), heart failure (n = 803), and kidney failure (n = 130). The addition of cystatin C, BTP, and B2M levels to models including eGFR(CKD-EPI) and all covariates, including urinary albumin-creatinine ratio, significantly improved risk prediction for all outcomes (P < 0.001).

Limitations: No direct measurement of GFR.

Conclusions: B2M and, to a lesser extent, BTP levels share cystatin C's advantage over eGFR(CKD-EPI) in predicting outcomes, including kidney failure. These additional markers may be helpful in improving estimation of risk associated with decreased kidney function beyond current estimates based on eGFR(CKD-EPI).

Figure 1

Adjusted relative hazard by marker quantile, adjusted for age, sex, race and field center. (A) death (1425 events in 9988 participants), (B) coronary heart disease (1279 events in 9988 participants), (C) heart failure (803 events in 9414 participants), (D) end-stage renal disease (130 events in 9936 participants). * p<0.05 for higher than Quantile 1. † p<0.05 for lower than Quantile 1.