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J Am Soc Nephrol 13:134-141, 2002
© 2002 American Society of Nephrology

Adiponectin, Metabolic Risk Factors, and Cardiovascular Events among Patients with End-Stage Renal Disease

Carmine Zoccali*, Francesca Mallamaci*, Giovanni Tripepi*, Francesco A. Benedetto{dagger}, Sebastiano Cutrupi*, Saverio Parlongo*, Lorenzo S. Malatino{ddagger}, Graziella Bonanno{ddagger}, Giuseppe Seminara§, Francesco Rapisarda{ddagger}, Pasquale Fatuzzo{ddagger}, Michele Buemi||, Giacomo Nicocia||, Sachiyo Tanaka, Noriyuki Ouchi, Shinji Kihara, Tohru Funahashi and Yuji Matsuzawa

*National Research Council Center of Clinical Physiology, Reggio Calabria, Italy; {dagger}Cardiology Division, Ospedale Morelli, Reggio Calabria, Italy; {ddagger}Departments of Internal Medicine and Nephrosurgery and §Institute of Internal Medicine and Geriatry, Catania University, Catania, Italy; ||Clinical Pathology and Nephrology Units, University of Messina, Messina, Italy; and Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan.

Correspondence to Dr. Carmine Zoccali, CNR Centro Fisiologia Clinica and Divisione di Nefrologia, Via Sbarre Inferiori 39, 89100, Reggio Calabria, Italy. Phone: 0039-965-397010; Fax: 0039-965-56005; E-mail: carmine.zoccali{at}diel.it

ABSTRACT. Adiponectin (ADPN), which is a secretory protein of adipose tissue, attenuates endothelial inflammatory responses in vitro. Among human subjects, plasma ADPN concentrations are reduced among patients with atherosclerotic complications but are substantially increased among patients with advanced renal failure. The clinical and biochemical correlates of plasma ADPN levels were investigated and the predictive power of ADPN levels with respect to survival rates and cardiovascular events was prospectively tested in a cohort of 227 hemodialysis patients, who were monitored for 31 ± 13 mo. Plasma ADPN levels were 2.5 times higher (P < 0.0001) among dialysis patients (15.0 ± 7.7 µg/ml) than among healthy subjects (6.3 ± 2.0 µg/ml), were independent of age, and were higher (P = 0.03) among women (15.2 ± 7.9 µg/ml) than among men (14.0 ± 7.4 µg/ml). For both genders, plasma ADPN levels were inversely related to body mass index values, plasma leptin levels, insulin levels, serum triglyceride levels, and homeostatic model assessment index values. Furthermore, plasma ADPN levels were directly related to HDL cholesterol levels and inversely related to von Willebrand factor levels. Plasma ADPN levels were lower (P < 0.05) among patients who experienced new cardiovascular events (13.7 ± 7.3 µg/ml) than among event-free patients (15.8 ± 7.8 µg/ml). There was a 3% risk reduction for each 1 µg/ml increase in plasma ADPN levels, and the relative risk of adverse cardiovascular events was 1.56 times (95% confidence interval, 1.12 to 1.99 times) higher among patients in the first ADPN tertile, compared with those in the third tertile. Plasma ADPN levels are an inverse predictor of cardiovascular outcomes among patients with end-stage renal disease. Furthermore, ADPN is related to several metabolic risk factors in a manner consistent with the hypothesis that this protein acts as a protective factor for the cardiovascular system.




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B. Bayes, M. C. Pastor, J. Bonal, A. Foraster, and R. Romero
Oxidative stress, inflammation and cardiovascular mortality in haemodialysis--role of seniority and intravenous ferrotherapy: analysis at 4 years of follow-up
Nephrol. Dial. Transplant., April 1, 2006; 21(4): 984 - 990.
[Abstract] [Full Text] [PDF]

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 Nephrol Dial TransplantHome page
R. Furuya, M. Odamaki, H. Kumagai, and A. Hishida
Beneficial effects of icodextrin on plasma level of adipocytokines in peritoneal dialysis patients
Nephrol. Dial. Transplant., February 1, 2006; 21(2): 494 - 498.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
F. Haugen, T. Ranheim, N. K. Harsem, E. Lips, A. C. Staff, and C. A. Drevon
Increased plasma levels of adipokines in preeclampsia: relationship to placenta and adipose tissue gene expression
Am J Physiol Endocrinol Metab, February 1, 2006; 290(2): E326 - E333.
[Abstract] [Full Text] [PDF]

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J. Malyszko, J. Malyszko, S. Wolczynski, and M. Mysliwiec
Adiponectin, leptin and thyroid hormones in patients with chronic renal failure and on renal replacement therapy: are they related?
Nephrol. Dial. Transplant., January 1, 2006; 21(1): 145 - 152.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
C. G. Schalkwijk, N. Chaturvedi, M. T. Schram, J. H. Fuller, C. D. A. Stehouwer, and the EURODIAB Prospective Complications Study Group
Adiponectin Is Inversely Associated with Renal Function in Type 1 Diabetic Patients
J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 129 - 135.
[Abstract] [Full Text] [PDF]

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 Arterioscler. Thromb. Vasc. Bio.Home page
H. Kato, H. Kashiwagi, M. Shiraga, S. Tadokoro, T. Kamae, H. Ujiie, S. Honda, S. Miyata, Y. Ijiri, J. Yamamoto, et al.
Adiponectin Acts as an Endogenous Antithrombotic Factor
Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 224 - 230.
[Abstract] [Full Text] [PDF]

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 Eur J EndocrinolHome page
P. W Peake, A. D Kriketos, L. V Campbell, Y. Shen, and J. A Charlesworth
The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals
Eur. J. Endocrinol., September 1, 2005; 153(3): 409 - 417.
[Abstract] [Full Text] [PDF]

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 British Journal of Diabetes & Vascular DiseaseHome page
B. Mukhopadhyay, N. Sattar, and M. Fisher
Review: Diabetes and cardiac disease in South Asians
The British Journal of Diabetes & Vascular Disease, September 1, 2005; 5(5): 253 - 259.
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 Diabetes CareHome page
R. Kahn, J. Buse, E. Ferrannini, and M. Stern
The Metabolic Syndrome: Time for a Critical Appraisal: Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes
Diabetes Care, September 1, 2005; 28(9): 2289 - 2304.
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 StrokeHome page
S. P. Efstathiou, D. I. Tsioulos, A. G. Tsiakou, Y. E. Gratsias, A. V. Pefanis, and T. D. Mountokalakis
Plasma Adiponectin Levels and Five-Year Survival After First-Ever Ischemic Stroke
Stroke, September 1, 2005; 36(9): 1915 - 1919.
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 Eur J EndocrinolHome page
T. Isobe, S. Saitoh, S. Takagi, H. Takeuchi, Y. Chiba, N. Katoh, and K. Shimamoto
Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study
Eur. J. Endocrinol., July 1, 2005; 153(1): 91 - 98.
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 Diabetes CareHome page
M. Saraheimo, C. Forsblom, J. Fagerudd, A.-M. Teppo, K. Pettersson-Fernholm, J. Frystyk, A. Flyvbjerg, P.-H. Groop, and on behalf of the FinnDiane Study Group
Serum Adiponectin Is Increased in Type 1 Diabetic Patients With Nephropathy
Diabetes Care, June 1, 2005; 28(6): 1410 - 1414.
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 J. Am. Soc. Nephrol.Home page
M. Saemann, T Weichhart, M Zeyda, G Staffler, M Schunn, K. Stuhlmeier, Y Sobanov, T. Stulnig, S Akira, A von Gabain, et al.
Immunoregulation in Urinary Tract Inflammation--A Role of Tamm-Horsfall Glycoprotein: Tamm-Horsfall Glycoprotein Links Innate Immune Cell Activation with Adaptive Immunity via a Toll-Like Receptor-4-Dependent Mechanism. J Clin Invest 115: 468-475, 2005
J. Am. Soc. Nephrol., April 1, 2005; 16(4): 829 - 836.
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 J. Am. Soc. Nephrol.Home page
B. Becker, F. Kronenberg, J. T. Kielstein, H. Haller, C. Morath, E. Ritz, D. Fliser, and for the MMKD Study Group
Renal Insulin Resistance Syndrome, Adiponectin and Cardiovascular Events in Patients with Kidney Disease: The Mild and Moderate Kidney Disease Study
J. Am. Soc. Nephrol., April 1, 2005; 16(4): 1091 - 1098.
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 Nephrol Dial TransplantHome page
E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw
Biochemical risk markers: a novel area for better prediction of renal risk?
Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508.
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 Arterioscler. Thromb. Vasc. Bio.Home page
R. S. Lindsay, H. E. Resnick, J. Zhu, M. L. Tun, B. V. Howard, Y. Zhang, J. Yeh, and L. G. Best
Adiponectin and Coronary Heart Disease: The Strong Heart Study
Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): e15 - e16.
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 CirculationHome page
D. M. Maahs, L. G. Ogden, G. L. Kinney, P. Wadwa, J. K. Snell-Bergeon, D. Dabelea, J. E. Hokanson, J. Ehrlich, R. H. Eckel, and M. Rewers
Low Plasma Adiponectin Levels Predict Progression of Coronary Artery Calcification
Circulation, February 15, 2005; 111(6): 747 - 753.
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 Eur J EndocrinolHome page
M. I. Yilmaz, A. Sonmez, S. Kilic, T. Celik, N. Bingol, M. Pinar, T. Mumcuoglu, and M. Ozata
The association of plasma adiponectin levels with hypertensive retinopathy
Eur. J. Endocrinol., February 1, 2005; 152(2): 233 - 240.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
M. B. Schulze, I. Shai, E. B. Rimm, T. Li, N. Rifai, and F. B. Hu
Adiponectin and Future Coronary Heart Disease Events Among Men With Type 2 Diabetes
Diabetes, February 1, 2005; 54(2): 534 - 539.
[Abstract] [Full Text] [PDF]

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 Nephrol Dial TransplantHome page
F. Guebre-Egziabher, J. Bernhard, T. Funahashi, A. Hadj-Aissa, and D. Fouque
Adiponectin in chronic kidney disease is related more to metabolic disturbances than to decline in renal function
Nephrol. Dial. Transplant., January 1, 2005; 20(1): 129 - 134.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
K. S.-L. Lam, A. Xu, K. C.-B. Tan, L.-C. Wong, S.-C. Tiu, and S. Tam
Serum Adiponectin Is Reduced in Acromegaly and Normalized after Correction of Growth Hormone Excess
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5448 - 5453.
[Abstract] [Full Text] [PDF]

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 Diabetes CareHome page
S. Wakabayashi and Y. Aso
Adiponectin Concentrations in Sera From Patients With Type 2 Diabetes Are Negatively Associated With Sympathovagal Balance as Evaluated by Power Spectral Analysis of Heart Rate Variation
Diabetes Care, October 1, 2004; 27(10): 2392 - 2397.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. Malyszko, J. S. Malyszko, S. Brzosko, S. Wolczynski, and M. Mysliwiec
Adiponectin Is Related to CD146, a Novel Marker of Endothelial Cell Activation/Injury in Chronic Renal Failure and Peritoneally Dialyzed Patients
J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4620 - 4627.
[Abstract] [Full Text] [PDF]


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