Authors' Disclosures of Potential Con

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sensitive cardiac troponin I assay results for early diagnosis ... diac troponin I (hs-cTnI) assay in an emergency department .... analytes, with longer half-life and.

Letters to the Editor Peter A. Kavsak2,3* Dennis T. Ko4 Xuesong Wang4 Andrew R. MacRae5 Allan S. Jaffe6

ious acute and nonacute populations to assess both the diagnostic and prognostic value of these new tests. Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

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Department of Pathology and Molecular Medicine, McMaster University Hamilton, ON, Canada 3 Discipline of Clinical Chemistry/Immunology Hamilton Regional Laboratory Medicine Program Henderson General Hospital (Core Lab Section) Hamilton, ON, Canada 4 Institute for Clinical Evaluative Sciences University of Toronto Toronto, ON, Canada 5 Department of Biochemistry and Medical Genetics, University of Manitoba Winnipeg, MB, Canada 6 Cardiovascular Division and Division of Laboratory Medicine Mayo Clinic, Rochester, MN

Authors’ Disclosures of Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest: Employment or Leadership: None declared. Consultant or Advisory Role: P.A. Kavsak, Ortho Clinical Diagnostics; A.R. MacRae, Beckman Coulter; A.S. Jaffe, Beckman Coulter, Siemens, Ortho Diagnostics, Singulex, Nanosphere, Inverness, Critical Diagnostics, GSK, Merck, and Hoffman-LaRoche. Stock Ownership: None declared. Honoraria: P.A. Kavsak, Beckman Coulter. Research Funding: Canadian Institutes of Health Research with reagents provided as an unrestricted grant by Beckman Coulter. P.A. Kavsak, Beckman Coulter. Expert Testimony: None declared. Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.

*Address correspondence to this author at: Hamilton Regional Laboratory Medicine Program Henderson General Hospital (Core Lab Section), 711 Concession St. Hamilton, ON Canada L8V 1C3 Fax 905-575-2581 E-mail [email protected]

References 1. Thygesen K, Alpert JS, White HD, on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the redefinition of myocardial infarction. Universal definition of myocardial infarction. J Am Coll Cardiol 2007;50:2173–95. 2. Apple FS, Pearce LA, Smith SW, Kaczmarek JM, Murakami MM. Role of monitoring changes in sensitive cardiac troponin I assay results for early diagnosis of myocardial infarction and prediction of risk of adverse events. Clin Chem 2009;55:930 –7. 3. Apple FS. A new season for cardiac troponin assays: it’s time to keep a scorecard. Clin Chem 2009;55:1303– 6. 4. Kavsak PA, MacRae AR, Yerna MJ, Jaffe AS. Analytic and clinical utility of a next-generation, highly sensitive cardiac troponin I assay for early detection of myocardial injury. Clin Chem 2009; 55:573–7. 5. Kavsak PA, Wang X, Ko D, MacRae AR, Jaffe AS. Short- and long-term risk stratification using a next-generation, high-sensitivity research cardiac troponin I (hs-cTnI) assay in an emergency department chest pain population. Clin Chem 2009;55:1809 –15.

Previously published online at DOI: 10.1373/clinchem.2009.136689

Influence of Blood Sampling Site on Intact Parathyroid Hormone Concentrations in Hemodialysis Patients To the Editor: Parathyroid hormone (PTH)1 concentrations must be deter-

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Nonstandard abbreviations: PTH, parathyroid hormone; HD, hemodialysis; SHPT, secondary hyperparathyroidism; iPTH, intact PTH; iPTH-c, iPTH measured from central blood sample; iPTH-p, iPTH measured from peripheral blood sample; CVC, central venous catheter; PHPT, primary hyperparathyroidism.

mined repeatedly in hemodialysis (HD) patients to evaluate secondary hyperparathyroidism (SHPT) and adjust the dosage of PTHlowering compounds (vitamin D or cinacalcet). Available PTH assays provide variable PTH results (1, 2 ) and may create uncertainty in therapeutic decision-making. Thus, there is a need to standardize PTH measurements as well as preanalytical conditions. To the best of our knowledge, the impact of the blood-sampling site on PTH determination for HD patients has not been investigated. We compared intact parathyroid hormone (iPTH) concentrations simultaneously measured in central (iPTH-c) and peripheral (iPTH-p) blood samples from CVC-bearing HD patients. We enrolled 30 HD patients [14 women, mean age 64 (SD 14) years, 16 men, mean age 77 (6) years] after receipt of informed consent. The local ethics committee approved the study. All patients had a central venous catheter (CVC), and none had an arteriovenous fistula. All CVCs were maintained open with 3.8% sodium citrate. Approximately 10 mL blood was simultaneously collected by 2 different nurses in Vacuette Serum Tubes with separator gel, the first from a tunneled CVC placed in the superior vena cava passing through the jugular vein, and the second from a peripheral (forearm) vein, before being connected to the extracorporeal circuit for HD. All samples were left to clot, transported on ice to the central laboratory, centrifuged at 2500g, and analyzed within 30 min. We measured baseline urea, creatinine, phosphorus, calcium, magnesium, and alkaline phosphatase activity using an Olympus AU2700 analyzer. We measured serum iPTH concentrations (10 – 65 pg/mL) using an immunochemiluminometric assay on a Roche Modular E 170 analyzer. Clinical Chemistry 56:3 (2010) 489

Letters to the Editor The intraassay CV of the iPTH assay was ⬍3%. We found no statistically significant difference between central and peripheral concentrations of urea, creatinine, phosphorus, calcium, magnesium, and alkaline phosphatase activity, biochemical markers of kidney and bone function (Wilcoxon test). Conversely, the concentrations of iPTH-c (median 229 ng/L, interquartile range 87–360 ng/L) and iPTH-p (median 144 ng/L, interquartile range 59 – 273 ng/L) differed significantly (Wilcoxon test, P ⬍ 0.001). Although there was a good correlation between each pair of values (P ⬍ 0.001), a significant difference (P ⫽ 0.001) in the absolute concentration was observed, with iPTH-c approximately 30% higher than iPTH-p. The mean difference (i.e., iPTH-c – iPTH-p) obtained by Bland–Altman analysis was 113 (155) ng/L. The PTH ratio (iPTHp/iPTH-c) was 0.72 (range 0.27– 1.04). No correlation between iPTH concentration and iPTH-p/ iPTH-c was found. The observed higher concentration of iPTH-c could be because CVC blood samples taken from the central catheter placed in the vein/cava immediately below the thyroid veins directly collect hormone just released by parathyroid cells. On the other hand, the lower iPTH-p concentrations could be caused by hormone degradation and hemodilution in the systemic circulation. Nevertheless, the concentration of the other measured analytes, with longer half-life and produced by the systemic metabolism instead of a topic pulsatile secretion, were not different between central and peripheral blood samples. Our study compared the influence of blood sampling site on iPTH concentrations in HD patients. Two studies reported intraoperative iPTH concentrations in 490 Clinical Chemistry 56:3 (2010)

peripheral or jugular veins in patients undergoing to parathyroidectomy for primary hyperparathyroidism (3, 4 ). Woodrum et al. (3 ) studied 201 patients with primary hyperparathyroidism (PHPT) who underwent single-gland parathyroidectomy. Blood samples were obtained peripherally in 114 patients and centrally from 87 patients. Subjects with central venous sampling had significantly higher PTH concentrations at baseline and at all collection times, before and after gland excision. However, the study was limited because compared patients who had either peripheral venous or central venous intraoperative PTH samples drawn. Beyer et al. (4 ), comparing simultaneous peripheral and central PTH concentrations in PHPT patients undergoing cervical exploration, showed higher absolute PTH concentrations in central venous samples. Our data are consistent with the data from these 2 studies. It should also be noted that, in HD patients, there can be substantial interference in PTH determinations by PTH fragments, normally cleared by the kidney, which represent up to 50% of the hormone concentration (5 ). Nephrologists should be aware of the difference in PTH concentrations between blood samples collected from central or peripheral sites. Clinical monitoring and therapy should be based on the same blood sample type.

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article. Authors’ Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts of interest.

Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.

References 1. Cantor T, Yang Z, Caraini N, Ilamathi E. Lack of comparability of intact parathyroid hormone measurements among commercial assays for end-stage renal disease patients: implication for treatment decisions. Clin Chem 2006;52: 1711– 6. 2. Joly D, Drueke TB, Alberti C, Houillier P, LawsonBody E, Martin KJ, Massart C, et al. Variation in serum and plasma PTH levels in secondgeneration assays in hemodialysis patients: a cross-sectional study. Am J Kidney Dis 2008;5: 987–95. 3. Woodrum DT, Saunders BD, England BG, Burney RE, Doherty GM, Gauger PG. The influence of sample site on intraoperative PTH monitoring during parathyroidectomy. Surgery 2004;136: 1169 –75. 4. Beyer TD, Chen E, Ata A, DeCresce R, Prinz RA, Solorzano CC. A prospective evaluation of the effect of sample collection site on intraoperative parathormone monitoring during parathyroidectomy. Surgery 2008;14:504 –9. 5. D’Amour P, Rakel A, Brossard JH, Rousseau L, Albert C, Cantor T. Acute regulation of circulating parathyroid hormone (PTH) molecular forms by calcium: utility of PTH fragments/PTH(1– 84) ratios derived from three generations of PTH assays. J Clin Endocrinol Metab 2006;91:283–9.

Carlo Vulpio2* Maurizio Bossola2 Dorina Speranza3 Cecilia Zuppi3 Giovanna Luciani2 Enrico Di Stasio3 1

Department of Surgery and 2 Istituto di Biochimica e Biochimica Clinica Catholic University of the Sacred Heart Rome, Italy

* Address correspondence to this author at: Istituto Clinica Chirurgica Universita` Cattolica S. Cuore L.go Gemelli 8 00168 Roma Italy Fax 039-06-30155491 E-mail [email protected] Previously published online at DOI: 10.1373/clinchem.2009.136754