Inflammation, oxidative stress, and obesity are important features associated with pathogenesis of cardiovascular disease, a major contributor to the mortality of hemodialysis (HD) patients. Apelin is an adipokine involved in a variety of physiological functions; however, little is known about apelin in chronic kidney disease (CKD). Thus, the purpose of this study was to analyze apelin plasma levels in HD patients and verify whether there is any relationship with inflammation, oxidative markers, and obesity. Twenty-four HD patients [53.6 ± 14.4 years, 14 men, and body mass index (BMI) of 25.0 ± 4.2 kg/m 2] were studied and compared with 15 healthy subjects (51.3 ± 13.5 years, 7 men, and BMI of 26.3 ± 3.7 kg/m 2). Plasma apelin-12 and -36 were measured using the enzyme immunometric assay method. Plasma electronegative low-density lipoprotein [LDL(-)] levels were measured using ELISA method, and tumor necrosis factor-α, interleukin-6, leptin, and plasminogen activator inhibitor-1 levels were measured by a multiplex assay kit. C-Reactive protein (CRP) was determined by immunoturbidimetry. Anthropometric data were also evaluated. There was no difference between apelin-36 levels in HD patients (0.82 ± 0.60 ng/mL) and healthy subjects (0.83 ± 0.23 ng/mL). In contrast, apelin-12 levels were significantly higher in patients (0.34 ± 0.15 ng/mL vs. 0.24 ± 0.13 ng/mL in healthy subjects). TNF-α, CRP, and LDL(-) levels were higher in patients; however, there was no correlation among apelin-12 or -36 and inflammatory or oxidative markers. The adiposity parameters were also not associated with apelin-12 or -36. In conclusion, plasma apelin seems to be not associated with cardiovascular risk in HD patients. Copyright © Informa Healthcare USA, Inc.345577581Tatemoto, K., Hosoya, M., Habata, Y., Fujii, R., Kakegawa, T., Zou, M.-X., Kawamata, Y., Fujino, M., Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor (1998) Biochemical and Biophysical Research Communications, 251 (2), pp. 471-476. , DOI 10.1006/bbrc.1998.9489O'Dowd, B.F., Heiber, M., Chan, A., Heng, H.H.Q., Tsui, L.-C., Kennedy, J.L., Shi, X., Nguyen, T., A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11 (1993) Gene, 136 (1-2), pp. 355-360. , DOI 10.1016/0378-1119(93)90495-OMedhurst, A.D., Jennings, C.A., Robbins, M.J., Davis, R.P., Ellis, C., Winborn, K.Y., Lawrie, K.W.M., Darker, J.G., Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin (2003) Journal of Neurochemistry, 84 (5), pp. 1162-1172. , DOI 10.1046/j.1471-4159.2003.01587.xO'Carroll, A.-M., Selby, T.L., Palkovits, M., Lolait, S.J., Distribution of mRNA encoding B78/apj, the rat homologue of the human APJ receptor, and its endogenous ligand apelin in brain and peripheral tissues (2000) Biochimica et Biophysica Acta - Gene Structure and Expression, 1492 (1), pp. 72-80. , DOI 10.1016/S0167-4781(00)00072-5, PII S0167478100000725Soltani Hekmat, A., Najafipour, H., Nekooian, A.A., Esmaeli- Mahani, S., Javanmardi, K., Cardiovascular responses to apelin in two-kidney-one-clip hypertensive rats and its receptor expression in ischemic and non-ischemic kidneys (2011) Regul Pept., 172, pp. 62-68Siddiquee, K., Hampton, J., Khan, S., Apelin protects against angiotensin II-induced cardiovascular fibrosis and decreases plasminogen activator inhibitor type-1 production (2011) J. Hypertens., 29, pp. 724-731Dray, C., Knauf, C., Daviaud, D., Apelin stimulates glucose utilization in normal and obese insulin-resistant mice (2008) Cell Metab., 8, pp. 437-445Yue, P., Jin, H., Aillaud, M., Apelin is necessary for the maintenance of insulin sensitivity (2010) Am. J. Physiol. Endocrinol. Metab., 298, pp. E59-E67Higuchi, K., Masaki, T., Gotoh, K., Chiba, S., Katsuragi, I., Tanaka, K., Kakuma, T., Yoshimatsu, H., Apelin, an APJ receptor ligand, regulates body adiposity and favors the messenger ribonucleic acid expression of uncoupling proteins in mice (2007) Endocrinology, 148 (6), pp. 2690-2697. , http://endo.endojournals.org/cgi/reprint/148/6/2690, DOI 10.1210/en.2006-1270Yue, P., Jin, H., Xu, S., Apelin decreases lipolysis via G(q), G(i), and AMPK-dependent mechanisms (2011) Endocrinology, 152, pp. 59-68Daviaud, D., Boucher, J., Gesta, S., TNFα up-regulates apelin expression in human and mouse adipose tissue (2006) FASEB Journal, 20 (9), pp. E796-E802. , http://www.fasebj.org/cgi/reprint/20/9/1528, DOI 10.1096/fj.05-5243fjeGarcia-Diaz, D., Campion, J., Milagro, F.I., Martinez, J.A., Adiposity dependent apelin gene expression: Relationships with oxidative and inflammation markers (2007) Molecular and Cellular Biochemistry, 305 (1-2), pp. 87-94. , DOI 10.1007/s11010-007-9531-5Hashimoto, T., Kihara, M., Imai, N., Yoshida, S.-I., Shimoyamada, H., Yasuzaki, H., Ishida, J., Umemura, S., Requirement of apelin-apelin receptor system for oxidative stress-linked atherosclerosis (2007) American Journal of Pathology, 171 (5), pp. 1705-1712. , DOI 10.2353/ajpath.2007.070471Melgar-Lesmes, P., Pauta, M., Reichenbach, V., Hypoxia and proinflammatory factors upregulate apelin receptor expression in human stellate cells and hepatocytes (2011) Gut., 60, pp. 1404-1411Stenvinkel, P., Inflammation in end-stage renal disease - A fire that burns within (2005) Contributions to Nephrology, 149, pp. 185-199. , DOI 10.1159/000085525, Cardiovascular Disorders in HemodialysisShastri, S., Sarnak, M.J., Cardiovascular disease and CKD: Core curriculum 2010 (2010) Am. J. Kidney Dis., 56, pp. 399-417Wratten, M.L., Galaris, D., Tetta, C., Sevanian, A., Evolution of oxidative stress and inflammation during hemodialysis and their contribution to cardiovascular disease (2002) Antioxidants and Redox Signaling, 4 (6), pp. 935-944Fouque, D., Kalantar-Zadeh, K., Kopple, J., Cano, N., Chauveau, P., Cuppari, L., Franch, H., Wanner, C., A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease (2008) Kidney International, 73 (4), pp. 391-398. , DOI 10.1038/sj.ki.5002585, PII 5002585Lohman, T.G., Roche, A.F., Martorell, R., (1991) Anthropometric Standardization Reference Manual, , Champaign, IL: Human Kinetics;Heymsfield, S.B., McManus, C., Smith, J., Anthropometric measurement of muscle mass: Revised equations for calculating bone-free arm muscle area (1982) American Journal of Clinical Nutrition, 36 (4), pp. 680-690Frisancho, A.R., (1990) Anthropometric Standards for the Assessments of Growth and Nutritional Status, p. 189. , Ann Arbor MI: University of Michigan;Executive summary of the expert panel on detection, evaluation, and treatment of high blood cholesterol in adults adult treatment panel III (2001) J. Am. Med. Assoc., 285, pp. 2486-2497. , NCEP (National Cholesterol Education ProgramValdez, R., A simple model-based index of abdominal adiposity (1991) J. Clin. Epidemiol., 44, pp. 955-956Lobo, J., Santos, F., Grosso, D., Electronegative LDL and lipid abnormalities in patients undergoing hemodialysis and peritoneal dialysis (2008) Nephron. Clin. Pract., 108, pp. 298-304Sargent, J., Gotch, F., Principles and biophysics of dialysis (1985) Replacement of Renal Function by Dialysis, 53. , Drukker W, Parsons F, Maher J, eds. 2nd ed. The Hague: Martinues Nijhoff;Castan-Laurell, I., Dray, C., Attané, C., Dupare, T., Knauf, C., Valet, P., Apelin, diabetes, and obesity (2011) Endocrine., 40, pp. 1-9Malyszko, J., Kozminski, P., Malszko, J., Mysliwiec, M., Type of arteriovenous fistula NYHA class and apelin in hemodialyzed patients (2011) Int. Urol. Nephrol., 43, pp. 185-190Malyszko, J., Malyszko, J.S., Kozminski, P., Mysliwiec, M., Apelin and cardiac function in hemodialyzed patients: Possible relations? (2006) American Journal of Nephrology, 26 (2), pp. 121-126. , DOI 10.1159/000092122El-Shehaby, A.M., El-Kathib, M.M., Battah, A.A., Roshdy, A.R., Apelin: A potential link between inflammation and cardiovascular disease in end stage renal disease patients (2010) Scand. J. Clin. Lab. Invest., 70, pp. 421-427Codognotto, M., Piccoli, A., Zaninotto, M., Mion, M., Vertolli, U., Tona, F., Boffa, G.M., Evidence for decreased circulating apelin beyond heart involvement in uremic cardiomyopathy (2007) American Journal of Nephrology, 27 (1), pp. 1-6. , DOI 10.1159/000098430Zhang, D.L., Liao, H., Wei, Y.Y., Zhang, Y., Zhang, Q.D., Wang, Z.G., Elevation of serum apelin-13 is positively correlated withADMA in patients on maintenance hemodialysis (2009) Clin. Nephrol., 71, pp. 405-412Malyszko, J., Malyszko, J.S., Mysliwiec, M., Visfatin and endothelial function in dialyzed patients (2010) Nephrology, 15, pp. 190-196O'Shea, M., Hansen, M.J., Tatemoto, K., Morris, M.J., Inhibitory effect of apelin-12 on nocturnal food intake in the rat (2003) Nutritional Neuroscience, 6 (3), pp. 163-167. , DOI 10.1080/1028415031000111273Boucher, J., Masri, B., Daviaud, D., Gesta, S., Guigne, C., Mazzucotelli, A., Castan-Laurell, I., Valet, P., Apelin, a newly identified adipokine up-regulated by insulin and obesity (2005) Endocrinology, 146 (4), pp. 1764-1771. , DOI 10.1210/en.2004-1427Tiani, C., Garcia-Pras, E., Mejias, M., Apelin signaling modulates splanchnic angiogenesis and portosystemic collateral vessel formation in rats (2009) J. Hepatol., 50, pp. 296-305Han, S., Wang, G., Qi, X., Lee, H.M., Englander, E.W., Greeley Jr., G.H., A possible role for hypoxia-induced apelin expression in enteric cell proliferation (2008) Am. J. Physiol. Regul. Integr. Comp. Physiol., 294, pp. R1832-R1839Geiger, K., Muendlein, A., Stark, N., Hypoxia induces apelin expression in human adipocytes (2011) Horm. Metab. Res., 43, pp. 380-385Glassford, A.J., Yue, P., Sheikh, A.Y., Chun, H.J., Zarafshar, S., Chan, D.A., Reaven, G.M., Tsao, P.S., HIF-1 regulates hypoxia- and insulin-induced expression of apelin in adipocytes (2007) American Journal of Physiology - Endocrinology and Metabolism, 293 (6), pp. E1590-E1596. , http://ajpendo.physiology.org/cgi/reprint/293/6/E1590, DOI 10.1152/ajpendo.00490.2007Valle, A., Hoggard, N., Adams, A.C., Roca, P., Speakman, J.R., Chronic central administration of apelin-13 over 10 days increases food intake, body weight, locomotor activity and body temperature in C57BL/6 mice (2008) Journal of Neuroendocrinology, 20 (1), pp. 79-84. , DOI 10.1111/j.1365-2826.2007.01617.xClarke, K.J., Whitaker, K.W., Reyes, T.M., Diminished metabolic responses to centrally-administered apelin-13 in diet-induced obese rats fed a high-fat diet (2009) J. Neuroendocrinol., 21, pp. 83-89Hung, W.W., Hsieh, T.J., Lin, T., Blockade of the reninangiotensin system ameliorates apelin production in 3T3-L1 adipocytes (2011) Cardiovasc. Drugs Ther., 25, pp. 3-12Foussal, C., Lairez, O., Calise, D., Activation of catalase by apelin prevents oxidative stress-linked cardiac hypertrophy (2010) FEBS Lett., 584, pp. 2363-2370Koken, T., Serteser, M., Kahraman, A., Gokce, C., Demir, S., Changes in serum markers of oxidative stress with varying periods of haemodialysis (2004) Nephrology, 9 (2), pp. 77-82. , DOI 10.1111/j.1440-1797.2004.00240.xVickers, C., Hales, P., Kaushik, V., Dick, L., Gavin, J., Tang, J., Godbout, K., Tummino, P., Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase (2002) Journal of Biological Chemistry, 277 (17), pp. 14838-14843. , DOI 10.1074/jbc.M200581200