Evaluation of Atherosclerosis and Arterial Stiffness with Angiogenic Growth Factors in Chronic Kidney Disease Patients

Yıl 2025, Cilt: 7 Sayı: 2, 314 - 321, 09.05.2025

Musa İlker Durak , Melahat Coban

https://doi.org/10.37990/medr.1603856

Öz

Aim: Cardiovascular (CV) complications are the most common cause of mortality in patients with chronic kidney disease (CKD).The study aimed to determine the relationship between angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) and atherosclerosis as determined by carotid artery intima-media thickness (CAT) and arterial stiffness (AS) as determined by brachial-ankle pulse wave velocity (bPWV) in pre-dialysis CKD patients.
Material and Method: The study included 126 (47.2%) male and 141 (52.8%) female pre-dialysis CKD patients. Presence of atherosclerosis was determined by CAT and presence of AS by bPWV. VEGF and Ang-2 serum levels were determined by enzyme-linked immunosorbent assays (ELISA).
Results: CAT, bPWV, and log10 Ang-2 values were significantly higher in patients compared to the healthy control group. Estimated glomerular filtration rate (eGFR), C-reactive protein (CRP), total cholesterol, triglycerides, CAT, and bPWV were higher and spot urine protein creatinine ratio was lower in patients with high mean log10 Ang-2 compared to the patients with low mean log10 Ang-2. There was a significant correlation between log10 Ang-2 and bPWV and CAT, and an inverse relationship with log10 VEGF.
Conclusion: Patients with CKD had increased development of atherosclerosis and AS, increased serum Ang-2 levels compared to healthy individuals. Ang-2 was significantly correlated with renal function and inversely correlated with proteinuria. Ang-2 was found to be correlated with inflammation and hyperlipidemia. A significant correlation was observed between Ang-2 and atherosclerosis and AS, and an inverse relationship was found with VEGF.

Anahtar Kelimeler

Atherosclerosis , arterial stiffness , chronic kidney disease , angiopoietin-2 , vascular endothelial growth factor

Etik Beyan

This study ethics committee numbered TABED 1-24-226 from Ankara City Hospital (date: 17/07/2024).

Teşekkür

tüm çalışma arkadaşlarımıza

Kaynakça

• Bots ML, Hofman A, De Jong PT, Grobbee DE. Common carotid intima-media thickness as an indicator of atherosclerosis at other sites of the carotid artery. The Rotterdam Study. Ann Epidemiol. 1996;6:147-53.
• Townsend RR, Wimmer NJ, Chirinos JA, et al. Aortic PWV in chronic kidney disease: a CRIC ancillary study. Am J Hypertens. 2010;23:282-9.
• Yamashina A, Tomiyama H, Takeda K, et al. Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. Hypertens Res. 2002;25:359-64.
• Matsunaga T, Warltier DC, Tessmer J, et al. Expression of VEGF and angiopoietins-1 and -2 during ischemia-induced coronary angiogenesis. Am J Physiol Heart Circ Physiol. 2003;285:H352-8.
• Lee KW, Lip GY, Blann AD. Plasma angiopoietin-1, angiopoietin-2, angiopoietin receptor tie-2, and vascular endothelial growth factor levels in acute coronary syndromes. Circulation. 2004;110:2355-60.
• Lorbeer R, Baumeister SE, Dörr M, et al. Circulating angiopoietin-2, its soluble receptor Tie-2, and mortality in the general population. Eur J Heart Fail. 2013;15:1327-34.
• Chang FC, Lai TS, Chiang CK, et al. Angiopoietin-2 is associated with albuminuria and microinflammation in chronic kidney disease. PLoS One. 2013;8:e54668.
• Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461-70.
• Yokoyama H, Shoji T, Kimoto E, et al. Pulse wave velocity in lower-limb arteries among diabetic patients with peripheral arterial disease. J Atheroscler Thromb. 2003;10:253-8.
• Homma S, Hirose N, Ishida H, et al. Carotid plaque and intima-media thickness assessed by b-mode ultrasonography in subjects ranging from young adults to centenarians. Stroke. 2001;32:830-5.
• Hara A, Wada T, Furuichi K, et al. Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in rat crescentic glomerulonephritis. Kidney Int. 2006;69:1986-95. Erratum in: Kidney Int. 2006;70:1666.
• Agyekum JA, Yeboah K. Angiopoietin-2 is associated with aortic stiffness in diabetes patients in Ghana: a case-control study. Int J Vasc Med. 2023;2023:3155982.
• Nadar SK, Blann A, Beevers DG, Lip GY. Abnormal angiopoietins 1&2, angiopoietin receptor Tie-2 and vascular endothelial growth factor levels in hypertension: relationship to target organ damage (a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)). J Intern Med. 2005;258:336-43.
• Futrakul N, Butthep P, Futrakul P. Altered vascular homeostasis in chronic kidney disease. Clin Hemorheol Microcirc. 2008;38:201-7.
• David S, Kümpers P, Hellpap J, et al. Angiopoietin 2 and cardiovascular disease in dialysis and kidney transplantation. Am J Kidney Dis. 2009;53:770-8.
• David S, Kümpers P, Lukasz A, et al. Circulating angiopoietin-2 levels increase with progress of chronic kidney disease. Nephrol Dial Transplant. 2010;25:2571-6.
• Fiedler U, Scharpfenecker M, Koidl S, et al. The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood. 2004;103:4150-6.
• Tsai YC, Chiu YW, Tsai JC, et al. Association of angiopoietin-2 with renal outcome in chronic kidney disease. PLoS One. 2014;9:e108862.
• Chong AY, Caine GJ, Freestone B, et al. Plasma angiopoietin-1, angiopoietin-2, and angiopoietin receptor tie-2 levels in congestive heart failure. J Am Coll Cardiol. 2004;43:423-8.
• Molnar MZ, Kümpers P, Kielstein JT, et al. Circulating Angiopoietin-2 levels predict mortality in kidney transplant recipients: a 4-year prospective case-cohort study. Transpl Int. 2014;27:541-52.
• Tsai YC, Lee CS, Chiu YW, et al. Angiopoietin-2 as a prognostic biomarker of major adverse cardiovascular events and all-cause mortality in chronic kidney disease. PLoS One. 2015;10:e0135181.
• Poredos P. Intima-media thickness: indicator of cardiovascular risk and measure of the extent of atherosclerosis. Vasc Med. 2004;9:46-54.
• Mayer G. Capillary rarefaction, hypoxia, VEGF and angiogenesis in chronic renal disease. Nephrol Dial Transplant. 2011;26:1132-7.
• Fiedler U, Reiss Y, Scharpfenecker M, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006;12:235-9.
• Upadhyay A, Hwang SJ, Mitchell GF, et al. Arterial stiffness in mild-to-moderate CKD. J Am Soc Nephrol. 2009;29:2044-53.
• Morimoto S, Yurugi T, Aota Y, et al. Prognostic significance of ankle-brachial index, brachial-ankle pulse wave velocity, flow-mediated dilation, and nitroglycerin-mediated dilation in end-stage renal disease. Am J Nephrol. 2009;30:55-63.
• David S, John SG, Jefferies HJ, et al. Angiopoietin-2 levels predict mortality in CKD patients. Nephrol Dial Transplant. 2012;27:1867-72.
• Chang FC, Chiang WC, Tsai MH, et al. Angiopoietin-2-induced arterial stiffness in CKD. J Am Soc Nephrol. 2014;25:1198-209.