Serum -Trace Protein and Risk of Mortality in Incident Hemodialysis Patients

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
Clinical Journal of the American Society of Nephrology (Impact Factor: 4.61). 06/2012; 7(9):1435-45. DOI: 10.2215/CJN.02240312
Source: PubMed


Residual kidney function in dialysis patients is associated with better survival, but there are no simple methods for its assessment. β-Trace protein is a novel endogenous filtration marker of kidney function that is not removed during hemodialysis and may serve as a marker for residual kidney function similar to serum creatinine in patients not on dialysis. The objective of this study was to determine the association of serum β-trace protein with mortality in incident hemodialysis patients.
Serum β-trace protein was measured in baseline samples from 503 participants of a national prospective cohort study of incident dialysis patients with enrollment during 1995-1998 and follow-up until 2004. Outcomes were all-cause and cardiovascular disease mortality analyzed using Cox regression adjusted for demographic, clinical, and treatment factors.
Serum β-trace protein levels were higher in individuals with no urine output compared with individuals with urine output (9.0±3.5 versus 7.6±3.1 mg/L; P<0.001). There were 321 deaths (159 deaths from cardiovascular disease) during follow-up (median=3.3 years). Higher β-trace protein levels were associated with higher risk of mortality. The adjusted hazard ratio and 95% confidence interval for all-cause mortality per doubling of serum β-trace protein was 1.36 (1.09-1.69). The adjusted hazard ratios (95% confidence intervals) for all-cause mortality in the middle and highest tertiles compared with the lowest tertile were 0.95 (0.69-1.32) and 1.72 (1.25-2.37). Similar results were noted for cardiovascular disease mortality.
The serum level of β-trace protein is an independent predictor of death and cardiovascular disease mortality in incident hemodialysis patients.

Download full-text


Available from: Bernard G Jaar, May 11, 2014
  • Source
    • "Inhibits inducible nitric oxide synthase Negoro et al. 2002 43 J Hypertens Suppresses expression of proinflammatory mediator PAI-1 Negoro et al. 2005 46 Life Sci Suppresses expression of vascular cell adhesion molecule 1 Rossi et al. 2000 48 Nature Activation of the nuclear receptor PPARg and inhibition of NF-kB activity Endothelial injury Taba et al. 2000 42 Circ Res Steady laminar shear stress stimulates BTP expression in endothelial cells, thereby inhibiting endothelial cell apoptosis Hypertension Hirawa et al. 2002 14 Hypertension BTP overexpression protects against cardiac overload Hypertensive CKD Bhavsar et al. 2011 26 Am J Kidney Dis Plasma BTP may be useful in evaluating risk of progression of kidney disease Vasospastic angina Matsumoto et al. 2011 16 Circ J BTP elevation is associated with the degree of coronary vasoconstriction (higher arterial shear stress) Acute decompensated heart failure Manzano-Fernández et al. 2011 15 J Am Coll Cardiol BTP predicts mortality, heart failure, hospitalization, and adverse cardiovascular events (These findings also apply to the next three studies.) Hemodialysis patients Shafi et al. 2012 30 CJASN General population Astor et al. 2012 27 Am J Kidney Dis Acute coronary syndromes Manzano-Fernández et al. 2012 17 Am J Cardiol ΑP, apoptosis protein; BTP, b-trace protein; PAI-1, plasminogen activator inhibitor-1; PPARg. peroxisome proliferator-activate receptor-g. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: To determine the relationship between maternal and neonatal cystatin C (CysC) and β-trace protein (BTP), markers of glomerular filtration rate (GFR) on day 1 of life. Methods: Blood levels of CysC, BTP, and creatinine (Cr) were analyzed from 128 healthy term and preterm neonates admitted to the neonatal intensive care unit (NICU) (36% female) to determine the relationship between gestational age and maternal levels on day 1 of life. Results: Maternal Cr correlated positively and significantly with neonatal Cr (r = 0.677, p < 0.0001) and CysC (r = 0.246, p < 0.012) on day 1 of life. Maternal BTP did not correlate with neonatal BTP. Gestational age correlated positively and significantly with neonatal Cr (0.427, p < 0.0001), CysC (r = 0.321, p = 0.001); and with maternal Cr (r = 0.452, p < 0.0001), CysC (r = 0.613, p < 0.0001), and BTP (r = 0.442, p < 0.0001). No correlation was found between gestational age and neonatal BTP. Upon considering the following age groups; 24 - 32, 33 - 36, and ≥ 37 weeks, maternal Cr continued to correlate with neonatal Cr, across all age groups, while no correlation was found with BTP, and CysC correlations were no longer significant. Throughout, neonatal values for CysC and BTP were higher, suggesting that low neonatal GFR was the main determinant for the variance. There was no difference in the median neonatal BTP across all age groups. Conclusion: Maternal Cr and CysC may both cross the placenta while BTP may not. Placental crossing of Cr seems to be independent of gestational age. The reasons for the different placental handling of BTP and CysC remain unknown.
    Clinical nephrology 02/2014; 81(4). DOI:10.5414/CN108089 · 1.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: β-trace protein, also known as Lipocalin type prostaglandin D synthase, is a low-molecular mass glycoprotein (between 23,000 and 29,000 Da depending on the degree of glycosylation) that converts prostaglandin H2 into prostaglandin D2. β-trace protein was initially isolated from cerebrospinal fluid and served as a marker of cerebrospinal fluid leakage; however, its cDNA and gene have been isolated in numerous human body tissues, including central nervous system, retina, melanocytes, heart, and male genital organs. In recent years, β-trace protein has emerged as a promising novel endogenous marker of GFR, representing a more sensitive marker for mild kidney dysfunction than serum creatinine. In this regard, β-trace protein has been proposed as an alternative marker to Cystatin C for measuring kidney function. Beyond its role for estimating renal function, β-trace protein is also emerging as a novel biomarker in cardiovascular risk. It has been associated with several cardiovascular disorders, playing a potential role for prognostic stratification in patients with acutely decompensated heart failure and acute coronary syndromes and being advocated as a novel marker for cardiovascular risk prediction.
    Clinical Journal of the American Society of Nephrology 01/2013; 8(5). DOI:10.2215/CJN.08870812 · 4.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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 m(2). 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.
    American Journal of Kidney Diseases 03/2013; 62(1). DOI:10.1053/j.ajkd.2013.01.016 · 5.90 Impact Factor
Show more