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Received on April 15, 2004
Accepted on August 17, 2004
Proteomics and Protein Markers |
1 Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis, MN.
2 Biostatistical Consulting, Minot, ND.
3 Department of Medicine, Minneapolis, MN.
* To whom correspondence should be addressed. E-mail: fred.apple{at}co.hennepin.mn.us.
Background: In patients with end-stage renal disease (ESRD), the ability of single and multiple biomarker monitoring to predict adverse outcomes has not been well established. This study determined the prognostic value of multiple biomarkers for all-cause death over 2 years in 399 ESRD patients.
Methods: The risk of all-cause death was determined by use of multiple biomarkers based on concentrations for a reference population (normal) and cutoffs based on tertile distributions in the ESRD group. Biomarkers studied included N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP; Dade Behring and Roche assays), and cardiac troponin T (cTnT; Roche) and I (cTnI; Dade Behring and Beckman Coulter assays). Relative risks of death were estimated and survival curves computed.
Results: A total of 101 deaths occurred during 594 patient-years of follow-up. Increased NT-proBNP concentrations were not predictive of death on the basis of the normal cutoffs. However, tertile analysis of NT-proBNP was significantly predictive of death and had an ROC area under the curve equivalent to or better than any of the other biomarkers. Biomarkers independently predictive of survival were hsCRP (P <0.001, either assay), cTnT (P <0.05), and cTnI (Dade, P <0.05). Two-year mortality rates were 6% (n = 45) with normal hsCRP, cTnI, and cTnT concentrations; 19% (n = 173) with increased hsCRP or cTnT and normal cTnI 44% (n = 160) with both hsCRP and cTnT increased and normal cTnI; 61% (n = 21) with increased cTnI (Dade) or 47% (n = 74) with increased cTnI (Beckman) regardless of hsCRP or cTnT concentrations. Defined by the normal cutoffs, increased concentrations of biomarkers were present in various proportions of the 399 patients with ESRD: NT-proBNP, 99%; hsCRP, 46% (both Roche and Dade assays); cTnT, 85%; cTnI, 19% (Beckman assay) and 5% (Dade assay).
Conclusions: Although mechanisms likely vary for causation, increased plasma hsCRP, cTnT, and cTnI above the cutoffs for our reference (normal) population were all independently predictive of subsequent death in ESRD patients. Tertile analysis for NT-proBNP also demonstrated prognostic value.
The following articles in journals at HighWire Press have cited this article:
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  V. HAJJAR and M. J. SCHREIBER JR. Q: Does measuring natriuretic peptides have a role in patients with chronic kidney disease? Cleveland Clinic Journal of Medicine, August 1, 2009; 76(8): 476 - 478. [Full Text] [PDF]
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 B.C. Astor, S. Yi, L. Hiremath, T. Corbin, V. Pogue, B. Wilkening, G. Peterson, J. Lewis, J.P. Lash, F. Van Lente, et al. N-Terminal Prohormone Brain Natriuretic Peptide as a Predictor of Cardiovascular Disease and Mortality in Blacks With Hypertensive Kidney Disease: The African American Study of Kidney Disease and Hypertension (AASK) Circulation, April 1, 2008; 117(13): 1685 - 1692. [Abstract] [Full Text] [PDF]
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F. S. Apple, A. S. Jaffe, and C. A. Herzog Letter Regarding Article by Khan et al, "Prognostic Value of Troponin T and I Among Asymptomatic Patients With End-Stage Renal Disease: A Meta-Analysis" Circulation, May 23, 2006; 113(20): e775 - e775. [Full Text] [PDF]
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