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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:147.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Low Circulating Endogenous Secretory Receptor for AGEs Predicts Cardiovascular Mortality in Patients With End-Stage Renal Disease

Hidenori Koyama; Tetsuo Shoji; Shinya Fukumoto; Kayo Shinohara; Takuhito Shoji; Masanori Emoto; Katsuhito Mori; Hideki Tahara; Eiji Ishimura; Ryusuke Kakiya; Tsutomu Tabata; Hiroshi Yamamoto; Yoshiki Nishizawa

From Department of Metabolism, Endocrinology, and Molecular Medicine (H.K., T.S., S.F., K.S., T.S., M.E., K.M., H.T., Y.N.), Department of Nephrology (E.I.), Osaka City University Graduate School of Medicine, Osaka, Japan; Division of Internal Medicine (R.K., T.T.), Inoue Hospital, Suita, Japan; Department of Biochemistry and Molecular Vascular Biology (H.Y.), Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

Correspondence to Hidenori Koyama, Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. E-mail hidekoyama{at}med.osaka-cu.ac.jp

Objective— Receptor for advanced glycation end-products (RAGE) is involved in diabetic vascular complications. We have recently shown that plasma endogenously secretory RAGE (esRAGE), an alternatively spliced form of RAGE, is closely associated with metabolic syndrome and atherosclerosis. Here, we evaluated if plasma esRAGE is a predictor of cardiovascular mortality in a cohort of 206 (171 nondiabetic) patients with end-stage renal diseases (ESRD).

Methods and Results— The cohort was followed for a median of 111 months, and 74 deaths including 34 cardiovascular deaths were recorded. Plasma esRAGE was measured at baseline. Cumulative incidence of cardiovascular death by Kaplan-Meier estimation was significantly higher in subjects in the lowest tertile of plasma esRAGE than those in the middle or the highest tertile both in all and nondiabetic subjects alone. In all subjects, as compared with the lowest tertile of plasma esRAGE, the hazards ratios for the highest and middle tertile were 0.40 (95% CI, 0.18 to 0.89) and 0.26 (0.10 to 0.66), respectively. The higher risk for lower esRAGE was still significant even after adjusted either with body mass index, hypertension, dyslipidemia and vascular complications, but was confounded by age and diabetes.

Conclusions— Low circulating esRAGE is a predictor for cardiovascular mortality in ESRD patients.

Plasma endogenously secretory receptor for AGEs (esRAGE), an alternatively spliced form of RAGE, is closely associated with metabolic syndrome and atherosclerosis. We showed here that low circulating plasma esRAGE is a predictor of cardiovascular mortality in a cohort of 206 patients with end-stage renal diseases.

Key Words: atherosclerosis • cardiovascular mortality • end stage renal diseases • epidemiology • receptor for AGEs • risk factors

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