Background/Aims: S100A12 induces vascular inflammation contributing to the development of atherosclerosis. Serum S100A12 concentration is shown to be elevated in patients with chronic kidney disease (CKD), however the reason remains unclear. Methods: Transcriptional levels of S100A12 and RAGE (receptor for advanced glycation end products) were measured in peripheral leukocytes by quantitative real-time RT-PCR. Subjects were 40 patients with CKD stage 4-5, 20 of whom were affected with cardiovascular disease (CVD), and 20 healthy subjects. Serum concentrations of S100A12 and soluble RAGE were measured using enzyme-linked immunosorbent assay. Results: The serum concentration of S100A12 was significantly higher in CKD patients than in healthy subjects (78.5 ± 70.5 vs. 23.7 ± 19.2 ng/ml, p = 0.0035), but that of soluble RAGE was not. The relative quantity of S100A12 mRNA was significantly greater in leukocytes from CKD patients than in those from healthy subjects [mean (95% confidence interval of the mean): 3.1 (2.2-3.9) vs. 1.2 (0.8-1.7), p = 0.0001], however that of RAGE mRNA was not. The serum concentration of S100A12 was significantly correlated with the relative quantity of S100A12 mRNA among uremic CKD patients (r2 = 0.656, p < 0.0001). Both the serum concentration and gene expression of S100A12 were significantly higher in patients who had CVD than in those who did not. Conclusion: Excessive expression of the S100A12 gene in uremic leukocytes is relevant to its increased serum concentration, particularly in those affected with CVD.

Donato R: S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 2001;33:637-668.
Hofmann MA, Drury S, Fu C, et al: RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 1999;97:889-901.
Burke AP, Kolodgie FD, Zieske A, et al: Morphologic findings of coronary atheroscrelotic plaques in diabetics: a postmortem study. Arterioscler Thromb Vasc Biol 2004;24:1266-1271.
Hofmann M, Wilk J, Heydemann A, et al: S100A12 mediates aortic wall remodeling and aortic aneurysm. Cir Res 2010;106:145-154.
Kosaki A, Hasegawa T, Kimura T, et al: Increased plasma S100A12 (EN-RAGE) levels in patients with type 2 diabetes. J Clin Endocrinol Metab 2004;89:5423-5428.
Shiotsu Y, Mori Y, Nishimura M, et al: Plasma S100A12 level is associated with cardiovascular disease in hemodialysis patients. Clin J Am Soc Nephrol 2011;6:718-723.
Mori Y, Kosaki A, Kishimoto N, et al: Increased plasma S100A12 (EN-RAGE) levels in hemodialysis patients with atherosclerosis. Am J Nephrol 2009;29:18-24.
Nakashima A, Carrero JJ, Qureshi AR, et al: Effect of circulating soluble receptor for advanced glycation end products (sRAGE) and the proinflammatory RAGE ligand (EN-RAGE, S100A12) on mortality in hemodialysis patients. Clin J Am Soc Nephrol 2010;5:2213-2219.
Uchiyama-Tanaka Y, Mori Y, Kosaki A, et al: Plasma S100A12 concentrations in peritoneal dialysis patients and subclinical chronic inflammatory disease. Ther Apher Dial 2008;12:28-32.
Kim JK, Park B, Lee MJ, et al: Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and proinflammatory ligand for RAGE (EN-RAGE) are associated with carotid atherosclerosis in patients with peritoneal dialysis. Atherosclerosis 2012;220:208-214.
Matsuo S, Imai E, Horio M, et al: Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009;53:982-992.
National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(suppl 1):S1-S26.
Rainen L, Oelmueller S, Jurgensen R, et al: Stabilization of mRNA expression in whole blood samples. Clin Chem 2002;48:1883-1890.
Espitia CM, Zhao W, Saldarriaga O, et al: Duplex real-time reverse transcriptase PCR to determine cytokine mRNA expression in a hamster model of New World cutaneous leishmaniasis. BMC Immunol 2010;11:31.
Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt Method. Methods 2001;25:402-408.
Schmittgen TD, Livak KJ: Analyzing real-time PCR data by the comparative CT method. Nat Proc 2008;3:1101-1108.
Hanford LE, Enghild JJ, Valnickova Z, et al: Purification and characterization of mouse soluble receptor for advanced glycation end products (sRAGE). J Biol Chem 2004;279:50019-50024.
Hasegawa T, Kosaki A, Kimura T, et al: The regulation of EN-RAGE (S100A12) gene expression in human THP-1 macrophages. Atherosclerosis 2003;171:211-218.
Goyette J, Yan WX, Yaman E, et al: Pleiotropic roles of S100A12 in coronary atherosclerotic plaque formation and rupture. J Immunol 2009;183:593-603.
Matsuoka E, Mori Y, Shiots Y, Kosaki A: THPO-127, 139A (accessed April, 2012).
Fink HA, Ishani A, Taylor BC, et al: Screening for monitoring and treatment of chronic kidney disease stages 1 to 3: a systematic review for the US Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline. Ann Intern Med 2012;156:570-581.
Ruggenenti P, Cravedi P, Remuzzi G: The RAAS in the pathogenesis and treatment of diabetic nephropathy. Nat Rev Nephrol 2010;6:319-330.
Raizada V, Hillerson D, Amaram JS, Skipper B: Angiotensin II-mediated left ventricular abnormalities in chronic kidney disease. J Investig Med 2012;60:785-791.
Kalousova M, Hodkova M, Kazderova M, et al: Soluble receptor for advanced glycation end products in patients with decreased renal function. Am J Kidney Dis 2006;47:406-411.
Basta G, Leonardis D, Mallamaci F, et al: Circulating soluble receptor of advanced glycation end product inversely correlates with atherosclerosis in patients with chronic kidney disease. Kidney Int 2010;77:225-231.
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.