Endothelial dysfunction is associated with visfatin and oxidative stress in hemodialysis patients

Endothelial dysfunction is associated with visfatin and oxidative stress in hemodialysis patients

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Title: Endothelial dysfunction is associated with visfatin and oxidative stress in hemodialysis patients
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Article_Title: Endothelial dysfunction is associated with visfatin and oxidative stress in hemodialysis patients
Authors: Remus Aurel Orasan, Simona Racasan, Raza Awon, Ioan Mihai Patiu, Ina Kacso, Diana Moldovan, Gabriel Samasca, Doina Daicoviciu, Adriana Muresan, Mirela Gherman Caprioara
Affiliation: Nefromed Dialysis Centers Cluj
“Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Nephrology Department
“Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Pediatrics Department
“Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Physiology Department
Abstract: Background: Endothelial dysfunction (ED) is marker of atherosclerosis in chronic renal failure. In uremia, visfatin was associated with inflammation and endothelial dysfunction. Materials and methods: We evaluated 32 chronic hemodialysis patients (group 1), divided in 2 subgroups (with and without diabetes mellitus) and 20 volunteers-control group (group 2). Plasma visfatin, endothelial-dependent flow-mediated vasodilatation and nitroglycerin-induced endothelium independent vasodilatation (NMD) were assessed for all groups. Malondialdehyde (MDA), hemoglobin, Kt/V, parathormone, C-reactive protein (CRP), albumin, ferritin, transferin saturation, cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, calcium, phosphorus and body mass index (BMI) were determined in group 1. Results: FMD (p=0.02) and NMD (p=0.01) were significantly higher in group 2 than in group 1. In group 1, FMD negatively correlated with visfatin (p=0.007) and MDA (=0.03) and positively correlated with LDL-cholesterol (p=0.0007). BMI, CRP and HDL-cholesterol were significantly higher (p=0.009, =0.001, =0.01 respectively) in diabetes patients compared to patients with no diabetes, while NMD, albumin and calcium were significantly lower (p=0.04, =0.003, =0.04 respectively). Conclusions: Endothelial dysfunction, measured by FMD, is increased in HD patients compared to controls and is associated with visfatin and oxidative stress. Diabetes mellitus is associated with NMD, but it does not influence FMD and visfatin, even if inflammation is enhanced in these patients.
Keywords: endothelial dysfunction, flow mediated dilatation, visfatin, hemodialysis, diabetes mellitus
References: Axelsson J, Stevinkel P, Role of fat mass and adipokines inchronic kideny disease. Curr Oppin Nephrol Hypertens,17, 25-31, 2008
Axelsson J, Witasp A, Carrero JJ, Qureshi AR, Suliman ME, Heimburger O, Barany P, Lindholm P, Alvestrand A, Schalling M, Nordfors L, Stevinkel P, Circulating levels of visfatin/Pre-B-cell colony-enhancing factor 1 in relation to genotype, GFR, body composition, and survival in patients with CKD. Am J Kidney Dis,49, 237-244, 2007
Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE, Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet, 340,1111-1115, 1992
Chen MP, Chung FM, Chang DM, Tsal JC, Huang HF, Shin SJ, Lee YJ, Elevated plasma level of visfatin – pre-B cell colony enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrin Metab, 91, 295-299, 2007
Costa-Hong V, Bortolotto LA, Jorgetti V, Consolim- Colombo F, Krieger EM, Lima JJ, Oxidative stress and endothelial dysfunction in chronic kidney disease. Arg Bras Cardiol, 92(5), 381-866, 398-403, 413-418, 2009
Del Vecchio L, Locatelli F, Carini M, What we know about oxidative stress in patients with chronic kidney disease on dialysis-clinical effects, potential treatment and prevention. Semin Dial, 24(1), 56-64, 2011
Fleming I, Annisuddin Mohamed, Jan Galle, Ljudmila Turchowa, Brandes RP, Fisslhaller B, Busse R, Oxidized low-density lipoprotein increases superoxide production by endothelial nitric oxide synthase by inhibiting PKCalfa. Cardiovascular Research, 65(4), 897-906, 2005
Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I, Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science, 307, 426-430, 2005
Haider DG, Schaller G, Kapiotis S, Maier C, Luger A, Woltz M, The release of the adipocytokine visfatin is regulated by glucose and insulin. Diabetologia, 49, 1909-1914, 2006
Kari JA, Donald AE, Vallance DT, Bruckdorfer KR, Leone A, Mullen MJ, Bunce T, Dorado B, Deanfield JE, Rees L, Physiology and biochemistry of endothelial function in children with chronic renal failure. Kidney Int, 52(2), 468-472, 1992
Kendrick J, Chonchol MB, Nontraditional risk factors for cardiovascular disease in patients with chronic kidney disease. Nature Reviews Nephrology, 4, 672-681, 2008
Lindner A, Charra B, Sherrad DJ, Scribner BH, Accelerated atherosclerosis in prolonged maintenance hemodialysis. N. Engl. J. Med, 290, 697-701, 1974
Malyszko J., Mechanism of endothelial dysfunction in chronic kidney disease. Clin Chim Acta 411(19-20), 1414-1420, 2010
Malyszko J, Malyszko JS, Mysliwiec M, Visfatin and endothelial dysfunction in dialyzed patients. Nephrology, 15, 190-196, 2010
Malyszko J, Malyszko JS, Wolczynski S, Brzosko S, Mysliwiec M, 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, 89, 4620-4627, 2004
Pagano C, Pilon C, Olivieri M, Mason P, Fabris R, Serra R, Milan G, Rossato M, Federspell G, Vettor R, Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans. J Clin Endocrinol Metab, 91(8), 3165-3170, 2006
Prasad N, Kumar S, Singh A, Sinha A, Chawla K, Gupta A, Sharma RK, Sinha N, Kapoor A, Carotid intimal thickness and flow-mediated dilatation in diabetic and nondiabetic continuous ambulatory peritoneal dialysis patients. Perit Dial Int, 29(Suppl 2), S96-S101, 2009
Recio-Mayoral A, Baneriee D, Streather C, Kaski JC, Endothelial dysfunction, inflammation and atherosclerosis in chronic kidney disease – a cross-sectional study of predialysis, dialysis and kidney-transplantation patients. Atherosclerosis Feb 18, 2011 [Epub ahead of print]
Rus R, Buturovic-Ponikvar J, Intima media thickness and endothelial function in chronic hemodialysis patients. Ther Apher Dial, 13(4), 294-299, 2009
Takami R, Takeda N, Hayashi M, Sasaki A, Kawachi S, Yoshino K, Yakami K, Nakashima K, Akai A, Yamakita K, Body fatness and fat distribution as predictors of metabolic abnormalities and early carotid atherosclerosis. Diabetes Care, 24, 1248-1252, 2001
Wang TD, Chen WJ, Cheng WC, Lin JW, Chen MF, Lee YT, Relation of improvement in endothelium- dependent flow-mediated vasodilation after rosiglitazone to changes in asymetric dimethylarginine, endothelin-1, and C-reactive protein in nondiabetic patients with the metabolic syndrome. Am J Cardiology, 98, 1057-1062, 2006
Yang H, Yang T, Baur JA, Perez E, Matsui T, Carmona JJ, lamming DW, Souza-Pinto NC, Bohr VA, Rosenzweig A, de Cabo R, Sauve AA, Sinclair DA, Nutrient-sensitive mitocondrial NAD+ levels dictate cell survival. Cell, 130(6), 1095-1107, 2007.
Yilmaz MI, Saglam M, Carrero JJ, Qureshi AR, Caglar K, Eyileten T, Sonmez A, Cakir E, Yenicesu M, Lindholm B, Stevinkel P, Axelsson J, Serum visfatin concentration and endothelial dysfunction in
chronic kidney disease. Nephrol Dial Transplant, 23, 959-965, 2008
Yilmaz MI, Saglam M, Qureshi AR, Carrero JJ, Caglar K, Eyileten T, Sonmez A, Cakir E, Oguz Y, Vural A, Yenicesu M, Stevinkel P, Lindholm B, Axelsson J, Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin. Nephrol Dial Transplant, 23(5), 1621-1627, 2008
Ziegelmeier M, bachmann A, Seeger J, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M, Adipokimes influencing metabolic and cardiovascular disease are differentially regulated in maintenance hemodialysis. Metabolism, 57(10), 1414-1421, 2008
Read_full_article: pdf/22-2012/22-2-2012/SU22-2-2012-Orasan.pdf
Correspondence: ORASAN REMUS AUREL, CENTRUL DE DIALIZA NEFROMED CLUJNAPOCA, STR. ANA ASLAN NR 40, COD POSTAL 400528, CLUJ-NAPOCA, Tel. 0744646831, Email: remusorasan@yahoo.com

Read full article
Article Title: Endothelial dysfunction is associated with visfatin and oxidative stress in hemodialysis patients
Authors: Remus Aurel Orasan, Simona Racasan, Raza Awon, Ioan Mihai Patiu, Ina Kacso, Diana Moldovan, Gabriel Samasca, Doina Daicoviciu, Adriana Muresan, Mirela Gherman Caprioara
Affiliation: Nefromed Dialysis Centers Cluj
“Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Nephrology Department
“Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Pediatrics Department
“Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Physiology Department
Abstract: Background: Endothelial dysfunction (ED) is marker of atherosclerosis in chronic renal failure. In uremia, visfatin was associated with inflammation and endothelial dysfunction. Materials and methods: We evaluated 32 chronic hemodialysis patients (group 1), divided in 2 subgroups (with and without diabetes mellitus) and 20 volunteers-control group (group 2). Plasma visfatin, endothelial-dependent flow-mediated vasodilatation and nitroglycerin-induced endothelium independent vasodilatation (NMD) were assessed for all groups. Malondialdehyde (MDA), hemoglobin, Kt/V, parathormone, C-reactive protein (CRP), albumin, ferritin, transferin saturation, cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, calcium, phosphorus and body mass index (BMI) were determined in group 1. Results: FMD (p=0.02) and NMD (p=0.01) were significantly higher in group 2 than in group 1. In group 1, FMD negatively correlated with visfatin (p=0.007) and MDA (=0.03) and positively correlated with LDL-cholesterol (p=0.0007). BMI, CRP and HDL-cholesterol were significantly higher (p=0.009, =0.001, =0.01 respectively) in diabetes patients compared to patients with no diabetes, while NMD, albumin and calcium were significantly lower (p=0.04, =0.003, =0.04 respectively). Conclusions: Endothelial dysfunction, measured by FMD, is increased in HD patients compared to controls and is associated with visfatin and oxidative stress. Diabetes mellitus is associated with NMD, but it does not influence FMD and visfatin, even if inflammation is enhanced in these patients.
Keywords: endothelial dysfunction, flow mediated dilatation, visfatin, hemodialysis, diabetes mellitus
References: Axelsson J, Stevinkel P, Role of fat mass and adipokines inchronic kideny disease. Curr Oppin Nephrol Hypertens,17, 25-31, 2008
Axelsson J, Witasp A, Carrero JJ, Qureshi AR, Suliman ME, Heimburger O, Barany P, Lindholm P,
Alvestrand A, Schalling M, Nordfors L, Stevinkel P, Circulating levels of visfatin/Pre-B-cell colony-enhancing factor 1 in relation to genotype, GFR, body composition, and survival in patients with CKD. Am J Kidney Dis,49, 237-244, 2007
Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE, Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet, 340,1111-1115, 1992
Chen MP, Chung FM, Chang DM, Tsal JC, Huang HF, Shin SJ, Lee YJ, Elevated plasma level of visfatin – pre-B cell colony enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrin Metab, 91, 295-299, 2007
Costa-Hong V, Bortolotto LA, Jorgetti V, Consolim- Colombo F, Krieger EM, Lima JJ, Oxidative stress and endothelial dysfunction in chronic kidney disease. Arg Bras Cardiol, 92(5), 381-866, 398-403, 413-418, 2009
Del Vecchio L, Locatelli F, Carini M, What we know about oxidative stress in patients with chronic kidney disease on dialysis-clinical effects, potential treatment and prevention. Semin Dial, 24(1), 56-64, 2011
Fleming I, Annisuddin Mohamed, Jan Galle, Ljudmila Turchowa, Brandes RP, Fisslhaller B, Busse R, Oxidized low-density lipoprotein increases superoxide production by endothelial nitric oxide synthase by inhibiting PKCalfa. Cardiovascular Research, 65(4), 897-906, 2005
Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S,
Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I, Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science, 307, 426-430, 2005
Haider DG, Schaller G, Kapiotis S, Maier C, Luger A, Woltz M, The release of the adipocytokine visfatin is regulated by glucose and insulin. Diabetologia, 49, 1909-1914, 2006
Kari JA, Donald AE, Vallance DT, Bruckdorfer KR, Leone A, Mullen MJ, Bunce T, Dorado B, Deanfield JE, Rees L, Physiology and biochemistry of endothelial function in children with chronic renal failure. Kidney Int, 52(2), 468-472, 1992
Kendrick J, Chonchol MB, Nontraditional risk factors for cardiovascular disease in patients with chronic kidney disease. Nature Reviews Nephrology, 4, 672-681, 2008
Lindner A, Charra B, Sherrad DJ, Scribner BH, Accelerated atherosclerosis in prolonged maintenance hemodialysis. N. Engl. J. Med, 290, 697-701, 1974
Malyszko J., Mechanism of endothelial dysfunction in chronic kidney disease. Clin Chim Acta 411(19-20), 1414-1420, 2010
Malyszko J, Malyszko JS, Mysliwiec M, Visfatin and endothelial dysfunction in dialyzed patients. Nephrology, 15, 190-196, 2010
Malyszko J, Malyszko JS, Wolczynski S, Brzosko S, Mysliwiec M, 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, 89, 4620-4627, 2004
Pagano C, Pilon C, Olivieri M, Mason P, Fabris R, Serra R, Milan G, Rossato M, Federspell G, Vettor R, Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans. J Clin Endocrinol Metab, 91(8), 3165-3170, 2006
Prasad N, Kumar S, Singh A, Sinha A, Chawla K, Gupta A, Sharma RK, Sinha N, Kapoor A, Carotid intimal thickness and flow-mediated dilatation in diabetic and nondiabetic continuous ambulatory peritoneal dialysis patients. Perit Dial Int, 29(Suppl 2), S96-S101, 2009
Recio-Mayoral A, Baneriee D, Streather C, Kaski JC, Endothelial dysfunction, inflammation and atherosclerosis in chronic kidney disease – a cross-sectional study of predialysis, dialysis and kidney-transplantation patients. Atherosclerosis Feb 18, 2011 [Epub ahead of print]
Rus R, Buturovic-Ponikvar J, Intima media thickness and endothelial function in chronic hemodialysis patients. Ther Apher Dial, 13(4), 294-299, 2009
Takami R, Takeda N, Hayashi M, Sasaki A, Kawachi S, Yoshino K, Yakami K, Nakashima K, Akai A, Yamakita K, Body fatness and fat distribution as predictors of metabolic abnormalities and early carotid atherosclerosis. Diabetes Care, 24, 1248-1252, 2001
Wang TD, Chen WJ, Cheng WC, Lin JW, Chen MF, Lee YT, Relation of improvement in endothelium- dependent flow-mediated vasodilation after rosiglitazone to changes in asymetric dimethylarginine, endothelin-1, and C-reactive protein in nondiabetic patients with the metabolic syndrome. Am J Cardiology, 98, 1057-1062, 2006
Yang H, Yang T, Baur JA, Perez E, Matsui T, Carmona JJ, lamming DW, Souza-Pinto NC, Bohr VA, Rosenzweig A, de Cabo R, Sauve AA, Sinclair DA, Nutrient-sensitive mitocondrial NAD+ levels dictate cell survival. Cell, 130(6), 1095-1107, 2007.
Yilmaz MI, Saglam M, Carrero JJ, Qureshi AR, Caglar K, Eyileten T, Sonmez A, Cakir E, Yenicesu M, Lindholm B, Stevinkel P, Axelsson J, Serum visfatin concentration and endothelial dysfunction in
chronic kidney disease. Nephrol Dial Transplant, 23, 959-965, 2008
Yilmaz MI, Saglam M, Qureshi AR, Carrero JJ, Caglar K, Eyileten T, Sonmez A, Cakir E, Oguz Y, Vural A, Yenicesu M, Stevinkel P, Lindholm B, Axelsson J, Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin. Nephrol Dial Transplant, 23(5), 1621-1627, 2008
Ziegelmeier M, bachmann A, Seeger J, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M, Adipokimes influencing metabolic and cardiovascular disease are differentially regulated in maintenance hemodialysis. Metabolism, 57(10), 1414-1421, 2008
*Correspondence: ORASAN REMUS AUREL, CENTRUL DE DIALIZA NEFROMED CLUJNAPOCA, STR. ANA ASLAN NR 40, COD POSTAL 400528, CLUJ-NAPOCA, Tel. 0744646831, Email: remusorasan@yahoo.com