Abstract
Purpose
Vascular access is vital for hemodialysis patients. A major factor that facilitates arteriovenous (AV) fistula failure is stenosis and thrombosis due to intimal hyperplasia developing in the venous segment of AV fistula. It has been reported that VEGF accelerated re-endothelialization, reduction in intimal thickening, and/or mural thrombus formed in the injured vascular structures. In this study, we aimed to identify the effect of the VEGF 936 gene polymorphism and vascular endothelial growth factor-A (VEGF-A) levels in the late period of AV fistula loss in hemodialysis patients.
Methods
The study was carried out with a patient group of 42 individuals who experienced two or more fistula thrombosis in the late period after the AV fistula operation and also a control group of 38 patients who have not had any AV fistula thrombosis history for 3 years or more. All participants were assessed for VEGF-936C/T gene polymorphism and VEGF-A levels.
Results
VEGF-936C/T genotypes were determined in the large proportion in the control group (31.6 %), while VEGF-936C/C genotypes were determined in a large proportion in the patient group (90.5 %). Individuals carrying the VEGF-936C/C genotype had an increased risk of 5.54 for getting AV fistula thrombosis. The VEGF-A levels of patient group (27.3 ± 43.5 pg/ml) were significantly lower than those of the control group (70.7 ± 53.1 pg/ml).
Conclusion
There is an increased risk of AV fistula thrombosis in individuals carrying the VEGF-936C/C genotype. The other renal replacement modalities should be considered in patients with this genotype. As a result, it will be possible to prevent the morbidity and mortality due to fistula failure.
Similar content being viewed by others
References
Brescia MJ, Cimino JE, Appel K, Hurwich BJ (1966) Chronic hemodialysis using venipuncture and a surgically created arteriovenosus fistula. N Engl J Med 275:1080–1092
Ravani P, Spergel LM, Asif A, Roy-Chaudhury P, Besarab A (2007) Clinical epidemiology of arteriovenous fistula in 2007. J Nephrol 20(2):141–149
Mendelssohn DC, Ethier J, Elder SJ, Saran R, Port FK, Pisoni RL (2006) Haemodialysis vascular access problems in Canada: result from the Dialysis Outcomes and Practice Patterns Study (DOPPS II). Nephrol Dial Transplant 21(3):721–728
Sajgure A, Choudhury A, Ahmed Z, Choudhury D (2007) Angiotensin converting enzyme inhibitors maintain polytetrafluroethylene graft patency. Nephrol Dial Transplant 22(5):1390–1398
Kats M, Hawxby AM, Barker J, Allon M (2007) Impact of obesity on arteriovenous fistula outcomes in dialysis patients. Kidney Int 71(1):39–43
Hayasi R, Huang E, Nissenson AR (2006) Vascular access for hemodialysis. Nat Clin Pract Nephrol 2(9):504–513
Roy-Chaudhury P, Lee TC (2007) Vascular stenosis and interventions. Curr Opin Nephrol Hypertens 16:516–522
Rotmans JI, Pasterkamp G, Verhagen HJM, Pattynama PMT, Blankestijn PJ, Stroes ESG (2005) Hemodialysis access graft failure: time to revisit an unmet clinical need? J Nephrol 18:9–20
Misra S, Fu AA, Puggioni A, Karimi KM, Mandrekar JN, Glockner JF et al (2008) Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts. Am J Physiol Heart Circ Physiol 294:2219–2230
Stracke S, Konner K, Köstlin I, Friedi R, Jehle PM, Hombach V et al (2002) Increased expression of TGF-beta1 and IGF-I in inflammatory stenotic lesions of hemodialysis fistulas. Kidney Int 61:1011–1029
Misra S, Fu AA, Rajan DK, Juncos LA, Mckusick MA, Bjarnason H et al (2008) The rat femoral arteriovenous fistula model: increased expression of matrix metalloproteinase-2 and -9 at the venous stenosis. Vasc Interven Radiol 19(4):587–594
Yla-Herttuala S, Rissansen TT, Vajanto I, Hartikainen J (2007) Vascular endothelial growth factors. Biology and current status of clinical applications in cardiovascular medicine. J Am Coll Cardiol 49:1015–1026
Clauss M (2000) Molecular biology of the VEGF and the receptor family. Semin Thromb Hemost 26:561–569
Ohtani K, Egashira K, Hiasa K, Kitamota S, Zhao Q, Ishibashi M et al (2004) Blockade of vascular endothelial growth factor suppresses experimental restenosis after intraluminal injury by inhibiting recruitment of monocyte lineage cells. Circulation 110:2444–2452
Zachary I, Mathur A, Yla-Herttuala S, Martin J (2000) Vascular protection a novel nonangiogenic cardiovascular role for vascular endothelial growth factor. Arterioscler Thromb Vasc Biol 20:1512–1520
Zohny SF, Abd el-Fattah M (2008) Evaluation of circulating vascular endothelial growth factor and soluble adhesion molecules as reliable predictors of native arteriovenous fistula thrombosis in chronic hemodialysis patients. Clin Biochem 41:1175–1180
Steffensen KD, Waldstrom M, Brandslund I, Jacobsen A (2010) The relationship of VEGF polymorphism with serum VEGF levels and progression-free survival in patients with epithelial ovarian cancer. Gynecol Oncol 117:109–116
Cosín R, Gilabert-Estellés J, Ramón LA, España F, Gilabert J, Romeu A, Estellés A (2009) Vascular endothelial growth factor polymorphisms(-460C/T, +405G/G, and 936C/T) and endometriosis: their influence on vascular endothelial growth factor expression. Fertil 92(4):1214–1220
Hayashi R, Huang E, Nissenson AR (2006) Vascular access for hemodialysis. Nat Clin Pract Nephrol 2(9):504–513
Güngör Y, Kayatas M, Yildiz G, Özdemir Ö, Candan F (2011) The presence of PAI-1 4G/5G and ACE DD genotypes increases the risk of early-stage AVF thrombosis in hemodialysis patients PAI-1 4G/5G and ACE DD genotypes and risk of early-stage AVF thrombosis. Ren Fail 33(2):169–175
Knoll GA, Wells PS, Young D, Perkins SL, Pilkey RM, Clinch JJ et al (2005) Thrombophilia and the risk for hemodialysis vascular access thrombosis. J Am Soc Nephrol 16(4):1108–1114
Lazo-Langner A, Knoll GA, Wells PS, Carson N, Rodger MA (2006) The risk of dialysis access thrombosis is related to the transforming growth factor-beta1 production haplotype and is modified by polymorphisms in the plasminogen activator inhibitor-type 1 gene. Blood 108(13):4052–4058
Moon JY, Jeong KH, Paik SS, Han JJ, Lee SH, Lee TW et al (2009) Arteriovenous fistula patency associated with angiotensin-converting enzyme I/D Arteriovenous fistula patency associated with angiotensin-converting enzyme I/D. Nephron Clin Pract 111:110–116
Windus DW (1993) Permanent vascular access: a nephrologist’s view. Am J Kidney Dis 21(5):457–471
Moist LM, Churchill DN, House AA, Millward SF, Elliot JE, Kribs SW et al (2003) Regular monitoring of access flow compared with monitoring of venous pressure fails to improve graft survival. J Am Soc Nephrol 14:2645–2653
Ferrara N (1999) Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int 56(3):794–814
Baumgartner I, İsner JM (2001) Somatic gene therapy in the cardiovascular system. Annu Rev Physiol 63:427–450
Roy H, Bhardwaj S, Ylä-Herttuala S (2006) Biology of vascular endothelial growth factors. FEBS Lett 580(12):2879–2887
Waltham M, Burnand K, Fenske C, Modarai B, Humphries J, Smith A (2005) Vascular endothelial growth factor naked DNA gene transfer enhances thrombus recanalization and resolution. J Vasc Surg 42(6):1183–1189
Modarai B, Humphries J, Burnand KG, Gossage JA, Waltham M, Wadoodi A et al (2006) Adenovirus-mediated VEGF gene therapy enhances venous thrombus recanalization and resolution. Arterioscler Thromb Vasc Biol 28(10):1753–1759
Awata T, Inoue K, Kurihara S, Ohkubo T, Watanabe M, Inukai K et al (2002) A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 51(5):1635–1639
Kim HW, Ko GJ, Kang YS, Lee MH, Song HK, Kim HK (2009) Role of the VEGF 936 C/T polymorphism in diabetic microvascular complications in type 2 diabetic patients. Nephrology 14:681–688
Renner W, Kotschan S, Hoffmann C, Obermayer-Pietsch B, Pilger E (2000) A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels. J Vasc Res 37(6):443–448
Eroglu A, Gulec S, Akar N (2007) Vascular endothelial growth factor C936T polymorphism in cancer patients with thrombosis. Am J Hematol 82(2):174
Kendall RL, Wang G, Thomas KA (1996) Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its hetero-dimerization with KDR. Biochem Biophys Res Commun 226(2):324–328
Prabir RC, Burnett SK, Ashwath N, Pankaj D, Murad M, Rino M et al (2002) Hemodialysis vascular access dysfunction from basic biology to clinical intervention. Adv Ren Replace Ther 9:74–84
Ku YM, Kim YO, Kim JI, Choi YJ, Yoon SA, Kim YS et al (2006) Ultrasonographic measurement of intima-media thickness of radial artery in pre-dialysis uraemic patients: comparison with histological examination. Nephrol Dial Transplant 21(3):715–720
Guo Q, Carrero JJ, Yu X, Bárány P, Qureshi AR, Eriksson M et al (2009) Associations of VEGF and its receptors sVEGFR-1 and -2 with cardiovascular disease and survival in prevalent haemodialysis patients. Nephrol Dial Transplant 24(11):3468–3473
Biuckians A, Scott EC, Meier GH, Panneton JM, Glickman MH (2008) The natural history of autologous fistulas as first-time dialysis access in the KDOQI era. J Vasc Surg 47(2):415–421
Mandus Ş, Katrancıoğlu N, Karahan O, Sapmaz İ, Doğan K (2008) Outcomes of arteriovenous fistula operations for hemodialysis performed by Cardiovascular Surgery Department of Cumhuriyet University. Cumhur Med J 30(1):28–32
Mallamaci F, Benedetto FA, Tripepi G, Cutrupi S, Pizzini P, Stancanelli B et al (2008) Vascular endothelial growth factor, left ventricular dysfunction and mortality in hemodialysis patients. J Hypertens 26(9):1875–1882
Felmeden DC, Spencer CG, Chung NA, Belgore FM, Blann AD, Beevers DG et al (2003) Relation of thrombogenesis in systemic hypertension to angiogenesis and endothelial damage/dysfunction (a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT]). Am J Hypertens 92:400–405
Stumpf C, Jukic J, Yilmaz A, Raaz D, Schmieder RE, Daniel WG et al (2009) Elevated VEGF-plasma levels in young patients with mild essential hypertension. Eur J Clin Invest 39(1):31–36
Gunsilius E, Petzer A, Stockhammer G, Nussbaumer W, Schumacher P, Clausen J et al (2000) Thrombocytes are the major source for soluble vascular endothelial growth factor in peripheral blood. Oncology 58(2):169–174
Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH (2003) Platelets and granulocytes, in particular neutrophils, from important compartments for circulating vascular endothelial growth factor. Angiogenesis 6:283–287
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Candan, F., Yildiz, G. & Kayataş, M. Role of the VEGF 936 gene polymorphism and VEGF-A levels in the late-term arteriovenous fistula thrombosis in patients undergoing hemodialysis. Int Urol Nephrol 46, 1815–1823 (2014). https://doi.org/10.1007/s11255-014-0711-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11255-014-0711-4