asymmetric dimethylarginine Table 1 CKD / 2 GFR 60 GFR(ml/min/1.73 m 2 )= age Cr Stage Definition GFR(ml/min/1.73

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1 Online publication January 14, 2011 総説第 50 回総会シンポジウム 2 循環器内科系 : 内皮と脈管疾患血管 - 腎連関と asymmetric dimethylarginine 要旨 : CKD: chronic kidney disease CKD Asymmeteric dimethylarginen ADMA ADMA ADMA ADMA CKD ADMA J Jpn Coll Angiol, 2010, 50: Key words: chronic kidney disease, endothelium, nitric oxide, nitric oxide synthase はじめに腎疾患と心血管疾患 2002 CKD: chronic kidney disease 1 CKD CKD CKD CKD NO CKD NO NO NOS asymmetric dimethylarginine ADMA CKD とは CKD GFR 60 ml/ /1.73 m 2 3 Table 1 6 CKD CKD THE JOURNAL of JAPANESE COLLEGE of ANGIOLOGY Vol. 50 No

asymmetric dimethylarginine Table 1 CKD 3 1 1 2 / 2 GFR 60 GFR(ml/min/1.73 m 2 )=0.741 175 age -0.203 Cr -1.154 0.742 Stage Definition GFR(ml/min/1.

2 asymmetric dimethylarginine Table 1 CKD / 2 GFR 60 GFR(ml/min/1.73 m 2 )= age Cr Stage Definition GFR(ml/min/1.73 m 2 ) <15 6 Figure 1 Clinical stages of chronic kidney disease. 6) Figure 2 Impact of chronic kidney disease on cardiovascular and renal death. modified from Ref [7] Fig. 1 GFR 60 ml/ /1.73 m 2 Fig. 2 7 CKD Fig. 3 8 CKD でなぜ心血管疾患が進展するのか CKD Fig. 6 4 Na Ca 660 脈管学 Vol. 50 No. 6

3 2 Figure 3 Impact of chronic kidney disease on 12-year cumulative cardiovascular event incidence (Hishayama study). modified from Ref [8] Figure 4 Possible mechanism of vasculo-renal syndrome. modified from Ref [6] CKD CKD CKD December 25,

4 asymmetric dimethylarginine Figure 5 Serum ADMA level was associated with carotid intima-media thickness in 116 healthy subjects (Tanushimaru study). modified from Ref [11] Figure 6 Serum ADMA level was an independent predictor for the progression of carotid atherosclerosis during 6-year follow-up study (Tanushimaru study). Adjusted for hypertension, hypercholesterolemia, diabetes mellitus, and smoking. modified from Ref [12] ADMA とは ADMA NOS 9 ADMA N G -monomethyl-l-arginine L-NMMA symmetric N G, N G -dimethyl-l-arginine SDMA protein arginine N-methyltransferase PRMT S-adenosylmethionine SAM ADMA L-NMMA NOS NOS enos inos nnos NO L-arginine NOS ADMA L-NMMA NOS NO L-arginine SDMA ADMA L-NMMA dimethylarginine dimethylaminohydrolase DDAH L- citrulline methylamine dimethylamine 9 DDAH 2 DDAH1 nnos DDAH2 enos DDAH NOS ADMA NOS ADMA と内皮障害 LDL ADMA ADMA 10 ADMA 11 Fig. 5 ADMA 6 Fig ADMA ADMA と CKD ADMA 13 ADMA 662 脈管学 Vol. 50 No. 6

5 ADMA ADMA ADMA CKD ADMA ADMA は血管 - 腎連関の分子機序に関与するのか ADMA ADMA DDAH ADMA NO ADMA NOS NOS ADMA NOS ADMA ADMA 5 CKD ADMA CKD ADMA さいごに CKD CKD CKD CKD ADMA CKD NOS CKD ADMA CKD ADMA 文献 1 K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Am J Kidney Dis, 2002, 39 (2 Suppl 1): S CKD Medical Practice Sarnak MJ, Levey AS, Schoolwerth AC et al: Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation, 2003, 108: Cheung AK, Sarnak MJ, Yan G et al: Cardiac diseases in maintenance hemodialysis patients: results of the HEMO Study. Kidney Int, 2004, 65: pdf2009/p017.pdf Keith DS, Nichols GA, Gullion CM et al: Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med, 2004, 164: Cooke JP: Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol, 2000, 20: Boger RH, Bode-Boger SM, Szuba A et al: Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation, 1998, 98: Miyazaki H, Matsuoka H, Cooke JP et al: Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation, 1999, 99: Furuki K, Adachi H, Enomoto M et al: Plasma level of asymmetric dimethylarginine (ADMA) as a predictor of carotid intima-media thickness progression: six-year prospective study using carotid ultrasonography. Hypertens Res, 2008, 31: Zoccali C, Bode-Boger S, Mallamaci F et al: Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet, 2001, 358: Zoccali C, Benedetto FA, Maas R et al: Asymmetric dime- December 25,

6 asymmetric dimethylarginine thylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease. J Am Soc Nephrol, 2002, 13: Zoccali C, Mallamaci F, Maas R et al: Left ventricular hypertrophy, cardiac remodeling and asymmetric dimethylarginine (ADMA) in hemodialysis patients. Kidney Int, 2002, 62: Yilmaz MI, Saglam M, Caglar K et al: Endothelial functions improve with decrease in asymmetric dimethylarginine (ADMA) levels after renal transplantation. Transplantation, 2005, 80: Role of Asymmetric Dimethylarginine in Vasculo-Renal Syndrome Hisashi Kai, 1 Hidemi Kajimoto, 2 and Tsutomu Imaizumi 1 1 Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University, Fukuoka, Japan 2 Department of Cardiovascular Research Institute, Kurume University, Fukuoka, Japan Key words: chronic kidney disease, endothelium, nitric oxide, nitric oxide synthase Chronic kidney disease (CKD) includes the wide disease spectrum from mild proteinuria and/or slightly reduced glomerular filtration rate to end-stage renal failure. CKD is not only a preliminary step for the progression of the kidney disease itself but also an independent risk factor for future cardiovascular events. However, the mechanism whereby CKD induces vascular and cardiac damages, leading to cardiovascular events, remains unknown at present. Nitric oxide (NO) is an established molecule that protect endothelial function and maintain the homeostasis of the cardiovascular system. Recently, asymmetric dimethylarginine (ADMA) has been highlighted as an endogenous inhibitor of NO synthases (NOSs). We review here the possible role of ADMA in the mechanism of the CKD-induced vascular damage known as vasculo-renal syndrome. (J Jpn Coll Angiol, 2010, 50: ) Online publication January 14, 脈管学 Vol. 50 No. 6

Table 1 Isolated venous thrombi in soleal muscle by ultrasonography US finding Acute Chronic Total No. Early stage non-retracted slightl

Table 1 Isolated venous thrombi in soleal muscle by ultrasonography US finding Acute Chronic Total No. Early stage non-retracted slightl Online publication October 8, 2010 原著第 50 回総会座長推薦論文孤立性ひらめ筋内静脈血栓と抗核抗体との関連 1 2 要旨 : 89 116 D 3 30 70 63 26 100 J Jpn Coll Angiol, 2010, 50: 417 422 Key words: isolated soleal venous thrombi, recurrent