Background: Soluble suppression of tumorigenicity 2 (sST2) is a novel cardiovascular biomarker. This study aimed to evaluate the prognostic value of sST2 in hemodialysis patients. Methods: Four hundred and fourteen maintenance hemodialysis (MHD) patients were enrolled and followed up prospectively. Serum sST2 levels were measured. The endpoint was all-cause and cardiovascular mortality. Results: During a median follow-up of 22.3 months, 58 patients died, including 31 cardiovascular deaths. sST2 was an independent predictor of all-cause mortality with a relative risk (RR) of 1.31 (95% CI 1.000-1.717, p = 0.050) and cardiovascular mortality with an RR of 2.10 (95% CI 1.507-2.927, p < 0.001). The prognostic value of sST2 was additive to N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT), as the combined use of sST2 and NT-proBNP or hs-cTnT better identified higher-risk patients. Conclusion: Elevated sST2 is an independent predictor of all-cause and cardiovascular mortality in MHD patients. A combined use of sST2 and NT-proBNP or hs-cTnT helps identify individuals of higher risk.

1.
Saran R, Li Y, Robinson B, Abbott KC, Agodoa LY, Ayanian J, Bragg-Gresham J, Balkrishnan R, Chen JL, Cope E, Eggers PW, Gillen D, Gipson D, Hailpern SM, Hall YN, He K, Herman W, Heung M, Hirth RA, Hutton D, Jacobsen SJ, Kalantar-Zadeh K, Kovesdy CP, Lu Y, Molnar MZ, Morgenstern H, Nallamothu B, Nguyen DV, O'Hare AM, Plattner B, Pisoni R, Port FK, Rao P, Rhee CM, Sakhuja A, Schaubel DE, Selewski DT, Shahinian V, Sim JJ, Song P, Streja E, Kurella Tamura M, Tentori F, White S, Woodside K, Hirth RA: US renal data system 2015 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis 2016;67(3 suppl 1):Svii, S1-S305.
2.
McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A: ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European society of cardiology. Developed in collaboration with the heart failure association (HFA) of the ESC. Eur Heart J 2012;33:1787-1847.
3.
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL: 2013 ACCF/AHA guideline for the management of heart failure: a report of the American college of cardiology foundation/American heart association task force on practice guidelines. J Am Coll Cardiol 2013;62:e147-e239.
4.
de Lemos JA: Increasingly sensitive assays for cardiac troponins: a review. JAMA 2013;309:2262-2269.
5.
Austin WJ, Bhalla V, Hernandez-Arce I, Isakson SR, Beede J, Clopton P, Maisel AS, Fitzgerald RL: Correlation and prognostic utility of B-type natriuretic peptide and its amino-terminal fragment in patients with chronic kidney disease. Am J Clin Pathol 2006;126:506-512.
6.
Pascual-Figal DA, Januzzi JL: The biology of ST2: the international ST2 consensus panel. Am J Cardiol 2015;115(7 suppl):3B-7B.
7.
Sanada S, Hakuno D, Higgins LJ, Schreiter ER, McKenzie AN, Lee RT: IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest 2007;117:1538-1549.
8.
Seki K, Sanada S, Kudinova AY, Steinhauser ML, Handa V, Gannon J, Lee RT: Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ Heart Fail 2009;2:684-691.
9.
Mueller T, Dieplinger B, Gegenhuber A, Poelz W, Pacher R, Haltmayer M: Increased plasma concentrations of soluble ST2 are predictive for 1-year mortality in patients with acute destabilized heart failure. Clin Chem 2008;54:752-756.
10.
Rehman SU, Mueller T, Januzzi JL Jr: Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure. J Am Coll Cardiol 2008;52:1458-1465.
11.
Ky B, French B, McCloskey K, Rame JE, McIntosh E, Shahi P, Dries DL, Tang WH, Wu AH, Fang JC, Boxer R, Sweitzer NK, Levy WC, Goldberg LR, Jessup M, Cappola TP: High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circ Heart Fail 2011;4:180-187.
12.
Bayes-Genis A, de Antonio M, Galán A, Sanz H, Urrutia A, Cabanes R, Cano L, González B, Díez C, Pascual T, Elosúa R, Lupón J: Combined use of high-sensitivity ST2 and NTproBNP to improve the prediction of death in heart failure. Eur J Heart Fail 2012;14:32-38.
13.
Kohli P, Bonaca MP, Kakkar R, Kudinova AY, Scirica BM, Sabatine MS, Murphy SA, Braunwald E, Lee RT, Morrow DA: Role of ST2 in non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 trial. Clin Chem 2012;58:257-266.
14.
Sabatine MS, Morrow DA, Higgins LJ, MacGillivray C, Guo W, Bode C, Rifai N, Cannon CP, Gerszten RE, Lee RT: Complementary roles for biomarkers of biomechanical strain ST2 and N-terminal prohormone B-type natriuretic peptide in patients with ST-elevation myocardial infarction. Circulation 2008;117:1936-1944.
15.
Dieplinger B, Egger M, Haltmayer M, Kleber ME, Scharnagl H, Silbernagel G, de Boer RA, Maerz W, Mueller T: Increased soluble ST2 predicts long-term mortality in patients with stable coronary artery disease: results from the Ludwigshafen risk and cardiovascular health study. Clin Chem 2014;60:530-540.
16.
Weinberg EO, Shimpo M, De Keulenaer GW, MacGillivray C, Tominaga S, Solomon SD, Rouleau JL, Lee RT: Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation 2002;106:2961-2966.
17.
Kakkar R, Lee RT: The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov 2008;7:827-840.
18.
Bartunek J, Delrue L, Van Durme F, Muller O, Casselman F, De Wiest B, Croes R, Verstreken S, Goethals M, de Raedt H, Sarma J, Joseph L, Vanderheyden M, Weinberg EO: Nonmyocardial production of ST2 protein in human hypertrophy and failure is related to diastolic load. J Am Coll Cardiol 2008;52:2166-2174.
19.
Demyanets S, Kaun C, Pentz R, Krychtiuk KA, Rauscher S, Pfaffenberger S, Zuckermann A, Aliabadi A, Gröger M, Maurer G, Huber K, Wojta J: Components of the interleukin-33/ST2 system are differentially expressed and regulated in human cardiac cells and in cells of the cardiac vasculature. J Mol Cell Cardiol 2013;60:16-26.
20.
Bao YS, Na SP, Zhang P, Jia XB, Liu RC, Yu CY, Mu SH, Xie RJ: Characterization of interleukin-33 and soluble ST2 in serum and their association with disease severity in patients with chronic kidney disease. J Clin Immunol 2012;32:587-594.
21.
Bayes-Genis A, Zamora E, de Antonio M, Galán A, Vila J, Urrutia A, Díez C, Coll R, Altimir S, Lupón J: Soluble ST2 serum concentration and renal function in heart failure. J Card Fail 2013;19:768-775.
22.
Mueller T, Gegenhuber A, Kronabethleitner G, Leitner I, Haltmayer M, Dieplinger B: Plasma concentrations of novel cardiac biomarkers before and after hemodialysis session. Clin Biochem 2015;48:1163-1166.
23.
Apple FS, Murakami MM, Pearce LA, Herzog CA: Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation 2002;106:2941-2945.
24.
Breidthardt T, Burton JO, Odudu A, Eldehni MT, Jefferies HJ, McIntyre CW: Troponin T for the detection of dialysis-induced myocardial stunning in hemodialysis patients. Clin J Am Soc Nephrol 2012;7:1285-1292.
25.
McIntyre CW, Burton JO, Selby NM, Leccisotti L, Korsheed S, Baker CS, Camici PG: Hemodialysis-induced cardiac dysfunction is associated with an acute reduction in global and segmental myocardial blood flow. Clin J Am Soc Nephrol 2008;3:19-26.
26.
Miller AM, Xu D, Asquith DL, Denby L, Li Y, Sattar N, Baker AH, McInnes IB, Liew FY: IL-33 reduces the development of atherosclerosis. J Exp Med 2008;205:339-346.
27.
Shen J, Shang Q, Wong CK, Li EK, Wang S, Li RJ, Lee KL, Leung YY, Ying KY, Yim CW, Kun EW, Leung MH, Li M, Li TK, Zhu TY, Yu SL, Kuan WP, Yu CM, Tam LS: IL-33 and soluble ST2 levels as novel predictors for remission and progression of carotid plaque in early rheumatoid arthritis: a prospective study. Semin Arthritis Rheum 2015;45:18-27.
28.
Li R, Yang G, Yang R, Peng X, Li J: Interleukin-33 and receptor ST2 as indicators in patients with asthma: a meta-analysis. Int J Clin Exp Med 2015;8:14935-14943.
29.
Yu XX, Hu Z, Shen X, Dong LY, Zhou WZ, Hu WH: IL-33 promotes gastric cancer cell invasion and migration via ST2-ERK1/2 pathway. Dig Dis Sci 2015;60:1265-1272.
30.
Lu DP, Zhou XY, Yao LT, Liu CG, Ma W, Jin F, Wu YF: Serum soluble ST2 is associated with ER-positive breast cancer. BMC Cancer 2014;14:198.
31.
Hladinova Z, Hruskova Z, Svobodova B, Malickova K, Lanska V, Konopásek P, Jancova E, Rysava R, Edelstein CL, Tesar V: Increased levels of soluble ST2 in patients with active newly diagnosed ANCA-associated vasculitis. Mediators Inflamm 2015;2015:603750.
32.
Gaggin HK, Szymonifka J, Bhardwaj A, Belcher A, De Berardinis B, Motiwala S, Wang TJ, Januzzi JL Jr: Head-to-head comparison of serial soluble ST2, growth differentiation factor-15, and highly-sensitive troponin T measurements in patients with chronic heart failure. JACC Heart Fail 2014;2:65-72.
33.
Manzano-Fernández S, Januzzi JL, Pastor-Pérez FJ, Bonaque-González JC, Boronat-Garcia M, Pascual-Figal DA, Montalban-Larrea S, Navarro-Peñalver M, Andreu-Cayuelas JM, Valdés M: Serial monitoring of soluble interleukin family member ST2 in patients with acutely decompensated heart failure. Cardiology 2012;122:158-166.
34.
Piper SE, Sherwood RA, Amin-Youssef GF, Shah AM, McDonagh TA: Serial soluble ST2 for the monitoring of pharmacologically optimised chronic stable heart failure. Int J Cardiol 2015;178:284-291.
35.
Maisel AS, Richards AM, Pascual-Figal D, Mueller C: Serial ST2 testing in hospitalized patients with acute heart failure. Am J Cardiol 2015;115(7 suppl):32B-37B.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.