Lalvani A, Pathan AA, Durkan H, Wilkinson KA, Whelan A, Deeks JJ,. Reece WH, Latif M, Pasvol G, Hill AV. Enhanced contact tracing and spatial tracking of ...
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References 1. Lalvani A, Pathan AA, Durkan H, Wilkinson KA, Whelan A, Deeks JJ, Reece WH, Latif M, Pasvol G, Hill AV. Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Lancet 2001;357:2017–2021. 2. Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med 2008;149:177–184. 3. Kik SV, Franken WPJ, Mensen M, Cobelens FGJ, Kamphorst M, Arend SM, Erkens C, Gebhard A, Borgdorff MW, Verver S. Predictive value for progression to tuberculosis by IGRA and TST in immigrant contacts. Eur Respir J 2010;35:1346–1353. 4. Diel R, Loddenkemper R, Niemann S, Meywald-Walter K, Nienhaus A. Negative and positive predictive value of a whole-blood IGRA for developing active TB: an update. Am J Respir Crit Care Med 2010;183:88–95. 5. Leung CC, Yam WC, Yew WW, Ho PL, Tam CM, Law WS, Au KF, Tsui PW. T-Spot.TB outperforms tuberculin skin test in predicting tuberculosis disease. Am J Respir Crit Care Med 2010;182:834–840.
Biomarkers in Community-acquired Pneumonia: Does Chronic Kidney Disease Matter? To the Editor:
We have read the interesting article by Kruger and coworkers (1) showing that select new biomarkers, such as midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), proarginin-vasopressin (copeptin), proendothelin-1 (CT-proET-1), and procalcitonin (PCT) are good predictors of either short- or long-term survival (superior to traditional inflammatory markers, and at least comparable to the CRB-65 score) in patients with community-acquired pneumonia (CAP). The authors acknowledged that the measurement of study biomarkers are potentially influenced by renal function, but it seems they failed to address this issue in their analysis. Recent evidence suggests that sex and eGFR are important confounding factors in the interpretation of copeptin levels in healthy subjects (2). In addition, copeptin is associated with accelerated renal function decline in renal transplant recipients (3). Higher levels of midregional proatrial natriuretic peptide were significantly associated with and greater urinary albumin-creatinine ratio in hypertensive patients (4). Finally, glomerular filtration rate (eGFR) was considered as a potential confounder when the prognostic significance of new biomarkers in patients with heart failure was investigated (5). In the light of the above findings, we have been surprised to see that eGFR was not estimated in the study by Kruger and colleagues. Furthermore, the authors do not report how the presence of chronic kidney disease was ascertained. In addition, it is not clear why the authors decided to adjust their multivariable models for comorbidity defined as the presence of one or more of selected disease, while only congestive heart failure, but not chronic kidney disease, was separately considered as a potential confounder. On the basis of this observation, we think that the authors might gain insight into the clinical meaning of individual biomarkers by entering eGFR into the multivariable model. Author Disclosure: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
ANDREA CORSONELLO, M.D. Italian National Research Center on Aging (INRCA) Cosenza, Italy FILIPPO LUCIANI, M.D. ‘‘Annunziata’’ Hospital Cosenza, Italy
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RAFFAELE ANTONELLI INCALZI, M.D. University Campus BioMedico Rome, Italy and San Raffaele Foundation, Cittadella della Carita Taranto, Italy References 1. Kruger S, Ewig S, Giersdorf S, Hartmann O, Suttorp N, Welte T. Cardiovascular and inflammatory biomarkers to predict short- and long-term survival in community-acquired pneumonia: results from the German Competence Network, CAPNETZ. Am J Respir Crit Care Med 2010;182:1426–1434. 2. Bhandari SS, Loke I, Davies JE, Squire IB, Struck J, Ng LL. Gender and renal function influence plasma levels of copeptin in healthy individuals. Clin Sci (Lond) 2009;116:257–263. 3. Meijer E, Bakker SJ, de Jong PE, Homan van der Heide JJ, van Son WJ, Struck J, Lems SP, Gansevoort RT. Copeptin, a surrogate marker of vasopressin, is associated with accelerated renal function decline in renal transplant recipients. Transplantation 2009;88:561–567. 4. Khaleghi M, Al-Omari MA, Kondragunta V, Morgenthaler NG, Struck J, Bergmann A, Mosley TH, Kullo IJ. Relation of plasma midregional proatrial natriuretic peptide to target organ damage in adults with systemic hypertension. Am J Cardiol 2009;103:1255–1260. 5. Neuhold S, Huelsmann M, Strunk G, Struck J, Adlbrecht C, Gouya G, Elhenicky M, Pacher R. Prognostic value of emerging neurohormones in chronic heart failure during optimization of heart failure-specific therapy. Clin Chem 2010;56:121–126.
From the Authors:
We thank Corsonello and coworkers for their comments. They raise the point that renal function might significantly impact biomarker levels, especially copeptin and atrial natriuretic peptide (ANP) (1). In our first study evaluating proANP and copeptin, we provided evidence that proANP and copeptin levels correlated with serum urea levels and calculated serum osmolarity, but not with serum sodium (2). We argued that the observed elevations in proANP and copeptin might be in part a result of renal failure related to severe CAP. However, in univariate and multivariate analysis, proANP and copeptin were much stronger and independent predictors of mortality compared with serum urea levels and history of renal disease. Corsonello and colleagues offer the criticism that eGFR was not estimated in our study. Unfortunately, creatinine—which is necessary to calculate eGFR—was not systematically collected in the CAPNETZ database. This decision was guided by the fact that the PSI score included serum urea nitrogen and history of renal disease, but not serum creatinine, because serum urea nitrogen and history of renal disease were independently associated with mortality in CAP (3). In our study, the presence of chronic renal disease was taken from patients’ history. Another concern raised by the authors is the failure to adjust our multivariable model for chronic renal disease. However, congestive heart failure was the only comorbidity found to be independently associated with mortality. To conclude, in future studies of patients with CAP renal function measurements, including serum creatinine and urea, should be included in the database because they may allow a more sophisticated interpretation of biomarkers for prognosis or therapeutic management. Author Disclosure: T.W. and S.E. have received research grants and lecture fees from Brahms. S.G. has received research grants and lecture fees from Brahms and is employed by ThermoFisher Brahms. O.H. is employed by Brahms GmbH; he holds stock in Thermo Fisher Scientific. None of the other authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
Correspondence Acknowledgment: This study was supported by the German Federal Ministry of Education and Research (Bundesministerium fu¨r Bildung und Forschung5BMBF), Grants 01KI0103-105, Competence Network CAPNETZ. The authors are grateful to the CAPNETZ study group1.
STEFAN KRU¨GER, M.D. RWTH University Aachen, Germany SANTIAGO EWIG, M.D. Ev. Krankenhaus Herne und Augusta Kranken-Anstalt Bochum, Germany SVEN GIERSDORF, PH.D. OLIVER HARTMANN BRAHMS AG Hennigsdorf, Germany NORBERT SUTTORP, M.D. Charite–University Medicine Berlin, Germany
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TOBIAS WELTE, M.D. Hannover Medical School, University Clinic Hannover, Germany AND THE CAPNETZ STUDY GROUP
References 1. Kru¨ger S, Ewig S, Giersdorf S, Hartmann O, Suttorp N, Welte T and The CAPNETZ Study group. Cardiovascular and inflammatory biomarkers to predict short- and long-term survival in communityacquired pneumonia: results from the German competence network CAPNETZ. Am J Respir Crit Care Med 2010;182:1426–1434. 2. Kru¨ger S, Papassotiriou J, Marre R, Richter K, Schumann C, von Baum H, Morgenthaler NG, Suttorp N, Welte T. Pro-atrial natriuretic peptide and pro-vasopressin to predict severity and prognosis in community-acquired pneumonia. Int Care Med 2007;33:2069–2078. 3. Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN. A prediction rule to identify lowrisk patients with community-acquired pneumonia. N Engl J Med 1997;336:243–250.
