Cardiovascular Features of Chronic Inflammation and Endothelial Dysfunction in Patients with Diabetic Nephropathy on Programmed Hemodialysis
DOI:
https://doi.org/10.12775/JEHS.2020.10.10.013Keywords
programmed hemodialysis, diabetic nephropathy, cardiovascular risk, proinflammatory mediators, endothelial damage, pathogenesisAbstract
Introduction and purpose: It is important today to determine the factors that form a very high cardiovascular risk in patients with type 2 diabetes mellitus (DM) with kidney damage on programmed hemodialysis (HD). The aim of the study has been to determine the cardiovascular features of chronic inflammation and endothelial dysfunction (ED) in HD patients with diabetic nephropathy (DN). Material and methods: The study has included 136 patients treated with HD (men, 78; age, 53.9±1.0 year, duration of HD, 47.6±4.2 months). Depending on the presence/absence of type 2 diabetes, they have been divided into two groups: the first – without DN (n=88); the second – with DN (n=48). The intensity of inflammation has been assessed by the serum content of tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), fibrinogen (FG) and albumin. Vasomotor function of the brachial artery (BA) has been determined using a test with reactive hyperemia (endothelium-dependent vasodilation, (EDVD)). The content of nitrite anions (NO2-) and the number of circulating endothelial cells (CECs) in blood plasma have been measured. Results: In patients with DN, TNF-α (p=0.002), CRP (p<0.001) and FG (p=0.008) significantly exceeded those in non-diabetics. The average value of EDVD BA (p=0.001), NO2- (p=0.008) in patients of the second group has been lower, and the number of CECs – higher (p<0.001) compared with the first group. Vasoconstriction (EDVD<0%) and undilatation (EDVD=0%) reactions in the case of DN have been registered more often (52.1 vs. 19.1%, p<0.001). In patients with DN for the first time have been established correlations between CECs and TNF-α (Rs=0.73, p<0.001), CRP (Rs=0.53, p<0.001), FG (Rs=0.53, p<0.001), albumin (Rs=-0.43, p=0.002). Conclusions: Chronic inflammation in the constellation with endothelial damage in patients with DN in the case of HD is obviously an important factor in cardiovascular remodeling, a predictor of progression of cardiovascular complications.
References
Zaoui P. Cardiovascular protection of diabetic patient with chronic renal disease and particular case of end-stage renal disease in elderly patients. Nephrol Ther, 2017;13(6S):6S16-6S24. doi: 10.1016 / S1769-7255 (18) 30036-1
Nardi E, Palermo A, Mulè G, Cusimano P, Cottone S, Cerasola G. Impact of type 2 diabetes on left ventricular geometry and diastolic function in hypertensive patients with chronic kidney disease. J Hum Hypertens, 2011;25(3):144-151. doi: 10.1038/jhh.2010.96
Susla OB, LitovkinaZI, Bushtynska OV. Strukturno-funktsionalni zminy sertsia u khvorykh na diabetychnu nefropatiiu, yaki perebuvaiut na khronichnomu hemodializi [Structural and functional changes of the heart in patients with diabetic nephropathy undergoing hemodialysis]. Ukr J Nephr Dial, 2019;4(64):39-48. doi: https://doi.org/10.31450/ukrjnd.4(64).2019.06 in Ukrainian
Avci E, Çakir E, Cevher S, Yaman H, Agilli M, Bilgi C. Determination of oxidative stress and cellular inflammation in patients with diabetic nephropathy and non-diabetic nephropathy being administered hemodialysis treatment due to chronic renal failure. Ren Fail, 2014;36(5):767-73. doi: 10.3109/0886022X.2014.890841
Hsu HJ, Yen ChH, Wu IW, Hsu KH, Chen ChK, Sun ChY, et al. The association of uremic toxins and inflammation in hemodialysis patients. PLoS One, 2014;9(7):1-14. doi: 10.1371/journal.pone.0102691
Susla OB, Litovkina ZI. Metabolichni faktory sertsevo-sudynnoho ryzyku u khvorykh iz diabetychnoiu nefropatiieiu na prohramnomu hemodializi [Metabolic factors of cardiovascular risk in patients with diabetic nephropathy who undergo programmed hemodyalisis]. Visnyk naukovykh doslidzhen, 2018;4(93):55-60. doi 10.11603/2415-8798.2018.4.9813 in Ukrainian
Mikhaylova NA, Tishkina SV, Ermolenko VM, Kertsev AM, Pushkina AV, Tishkina AV. Particularities of nutritional status in patients with diabetes mellitus on maintenance hemodialysis. Nephrology and Dialysis, 2020;22(2). doi: 10.28996 / 2618-9801-2020-2-189-197 [in Russian]
Jakuszewski P, Czerwieńska B, Chudek J, Wiecek A. Which components of malnutrition-inflammation-atherosclerosis syndrome are more common in haemodialysis patients with diabetic nephropathy? Nephrology (Carlton), 2009;14(7):643-649. doi: 10.1111/j.1440-1797.2009.01096.x
Susla OB Aktyvnist khronichnoho zapalennia i poshkodzhennia endoteliiu u khvorykh iz kaltsyfikatsiieiu klapaniv sertsia pry dializ-zalezhnii khronichnii khvorobi nyrok [Activity of chronic inflammation and endothelial damage in patients with cardiac valve calcification in dialysis-dependent chronic kidney disease]. Ukr J Nephr Dial, 2014;4(44):59-64. http://nbuv.gov.ua/UJRN/Uzhn_2014_4_8 [in Ukrainian]
Paulus W, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. Am Coll Cardiol, 2013;62(4):263-71. doi: 10.1016/j.jacc.2013.02.092
Daugirdas J. Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. JASN, 1993;4(5):1205-1213. https://jasn.asnjournals.org/ content/jnephrol/4/5/1205.full.pdf?with-ds=yes
Hladovec J, Prerovsky I, Stanek V, Fabian J. Circulating endothelial cells in acute myocardial infarction and angina pectoris. Klin Wochenshr, 1978;56(20):1033-1036. doi: 10.1007/bf01476669
Green L, Wagner D, Glogowski J, Skipper P, Wishnok J, Tannenbaum S. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem, 1982;126(1):131-138. doi: 10.1016/0003-2697(82)90118-x
Celermajer D, Sorensen K, Gooch V, Spiegelhalter D, Miller O, Sullivan I, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk atherosclerosis. Lancet, 1992;340(7):1111-1115. doi: 10.1016/0140-6736(92)93147-f
Taslipinar A, Yaman H, Yilmaz M, Demirbas S, Saglam M, Taslipinar M, et al. The relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy. Scand J Clin Lab Invest, 2011;71(7):606-612. doi: 10.3109/00365513.2011.598944
Zhuravlyova LV, Pylov DI. Znachennia spivvidnoshennia faktoru nekrozu pukhlyn-α ta vaspinu v rozvytku insulinorezystentnosti [The value of the tumor necrosis factor-alpha and vaspin ratio in the development of insulin resistance]. Problemy endokrynnoi patolohii, 2019;3:113-120. https://jpep.endocrinology.org.ua/uploads/pdf/19/11/13/c5f4e2b0.pdf [in Ukrainian]
Carlsson A, Östgren C, Nystrom F, Länne T, Jennersjö P, Larsson A, et al. Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes. Cardiovasc Diabetol, 2016;29(2):15-40. doi: 10.1186/s12933-016-0359-8
Bashir H, Bhat S, Majid S, Hamid R, Koul R, Rehman M, et al. Role of inflammatory mediators (TNF-α, IL-6, CRP), biochemical and hematological parameters in type 2 diabetes mellitus patients of Kashmir, India. Med J Islam Repub Iran, 2020;34:5. doi: 10.34171/mjiri.34.5
Yen TH, Lin JaL, Lin-Tan DT, Hsu KH. Cardiothoracic ratio, inflammation, malnutrition, and mortality in diabetes patients on maintenance hemodialysis. Am J Med Sci, 2009;337(6):421-428. doi: 10.1097/MAJ.0b013e31819bbec1
Chang Ch, Chien M, Yang K, Yu Ch, Hsu J, Wang I, et al. Nitric oxide production and blood pressure reduction during haemodialysis. Nephrology (Carlton), 2014;19(9):562-567. doi: 10.1111/nep.12280
Ramseyer V, Garvin J. Tumor necrosis factor-α: regulation of renal function and blood pressure. Am J Physiol Renal Physiol., 2013;304(10):F1231–F1242. doi.org/10.1152/ajprenal.00557.2012
Almeida A, Lourenço O, Fonseca A. Haemodialysis in diabetic patients modulates inflammatory cytokine profile and T cell activation status. Scand J Immunol, 2015;82(2):135-141. doi: 10.1111/sji.12309
Dudar IО. Cystemne khronichne zapalennia u khvorykh na khronichnu khvorobu nyrokta mozhlyvi likuvalni pidkhody [Systemic chronic inflammation in end-stage renal disease patients and possible treatment approaches]. Ukr J Nephr Dial, 2020;2(66):52-61. doi: https://doi.org/10.31450/ukrjnd.2(66).2020.08 [in Ukrainian]
Joussen A, Doehmen S, Le M, Koizumi K, Radetzky S, Krohne T, et al. TNF-α mediated apoptosis plays an important role in the development of early diabetic retinopathy and long-term histopathological alterations. Mol Vis, 2009;15:1418–1428. http://www.molvis.org/molvis/v15/a15
Neumann Р, Gertzberg N, Johnson A. TNF-alpha induces a decrease in eNOS promoter activity. Am J Physiol Lung Cell Mol Physiol, 2004;286(2):L452-L459. doi: 10.1152/ajplung.00378.2002
Hadi A, Suwaidi J. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag, 2007;3(6):853–876. PMC2350146
Malyszko J. Mechanism of endothelial dysfunction in chronic kidney disease. Clin Chim Acta, 2010;411(19-20):1412-1420. doi: 10.1016/j.cca.2010.06.019
Topchij II, Kirienko AN, Shhenjavskaja EN, Efimova NV, Bondar TN, Lesovaja AV. Soderzhanie cirkulirujushhih kletok jendotelija, VE-kadgerina i stabil'nyh metabolitov oksida azota u bol'nyh hronicheskoj bolezn'ju pochek i gipertonicheskoj bolezn'ju v dinamike lechenija s primeneniem L-arginina. Sіmejna medicina, 2010;3:35-39. https://www.uf.ua/wp-content/ uploads/2017/03/99d1f0b3a4fc227cd31203187370ce78.pdf [in Russian]
Chen HY , Chiu YL, Hsu SP, Pai MF, Lai CF, Yang JY, et al. Elevated C-reactive protein level in hemodialysis patients with moderate/severe uremic pruritus: a potential mediator of high overall mortality. QJM, 2010;103(11):837-846. doi: 10.1093/qjmed/hcq036
Susla OB, Hozhenko AI, Berhier Y, Mysula IR, Shved MI, Lykhodid OM. Kaltsyfikatsiia sertsia i sudyn pry khronichnii khvorobi nyrok: problemni pytannia etiolohii i patohenezu [Calcification of heart and vessels in chronic kidney disease: Problems of etiology and pathogenesis]. Fiziol zhurn, 2017;63(5):80-93. https://fz.kiev.ua/journals/2017_V.63/2017_5/5-80-93.pdf [in Ukrainian]
Radajkina O, Vlasov A, Myshkina N. Rol' jendotelial'noj disfunkcii v patologii serdechno-sosudistoj sistemy [Role of endothelial dysfunction in cardiovascular system pathology]. Ul'janovskij mediko-biologicheskij zhurnal, 2018;4:8-17. doi 10.23648/UMBJ.2018.32.22685 [in Russian]
Lapchinskaja II, Kishko RM, Semenec EL. Hronicheskoe vospalenie u pacientov na gemodialize [The chronic inflammation in hemodialysis patients]. Ukr J Nephr Dil., 2009;1(21):52-59. http://nbuv.gov.ua/UJRN/Uzhn_2009_1_11 [in Russian]
Talari HR, Zakizade M, Soleimani A, Bahmani F, Ghaderi A, Mirhosseini N, et al. Effects of magnesium supplementation on carotid intima-media thickness and metabolic profiles in diabetic haemodialysis patients: a randomised, double-blind, placebo-controlled trial. Br J Nutr, 2019;121(7):809-817. doi: 10.1017/S0007114519000163
Maier J, Malpuech-Brugere C, Zimowska W, Rayssiguier Y, Mazur A. Low magnesium promotes endothelial cell dysfunction: implications for atherosclerosis, inflammation and thrombosis. Biochim Biophys Acta, 2004;1689(1):13-21. doi: 10.1016/j.bbadis.2004.01.002
Susla O, Litovkina Z, Gozhenko A, Shved M, Danyliv S. Hypomagnesemia as important component of atherosclerosis progression in type 2 diabetic patients with end-stage renal disease. Cardionephrology 2019; March 12-14, Rome, Italy; 2019. https://fenicia-events.eu/ cardionefro/en/abstract-2/
Hwang HS, Cho JS, Hong YA, Chang YK, Kim SY, Shin SJ, et al. Vascular calcification and left ventricular hypertrophy in hemodialysis patients: interrelationship and clinical impacts. Int J Med Sci., 2018;15(6):557-563. doi: 10.7150/ijms.23700
Carmona A, Agüera M, Luna-Ruiz C, Buendía P, Calleros L, García-Jerez A, et al. Markers of endothelial damage in patients with chronic kidney disease on hemodialysis. Am J Physiol Renal Physiol, 2017;312(4):F673-F681. doi: 10.1152/ajprenal.00013.2016
Hassan M, Duarte R, Dix-Peek T, Vachiat A, Naidoo S, Dickens C, et al. Correlation between volume overload, chronic inflammation, and left ventricular dysfunction in chronic kidney disease patients. Clin Nephrol, 2016;86(13):131-135. doi: 10.5414/CNP86S127
Erten Y, Tulmac M, Derici U, Pasaoglu H, Altok Reis K, Bali M, et al. An association between inflammatory state and left ventricular hypertrophy in hemodialysis patients. Ren Fail, 2005;27(5):581-589. doi:10.1080/08860220500200072
Mostovaya I, Bots M, van den Dorpel M, Goldschmeding R, den Hoed C, Kamp O, et al. Left ventricular mass in dialysis patients, determinants and relation with outcome. results from the COnvective TRansport STudy (CONTRAST). PLoS One, 2014;9(2). doi: 10.1371/journal.pone.0084587
Driianska VYe, Korol LV, Dudar IO, Myhal LYa, Honchar YuI, Shifris IM, et al. Prozapalni tsytokiny (IL-1β, FNP-α) ta oksydantnoantyoksydantnyi balans krovi khvorykh na khronichnu khvorobu nyrok v d stadii z riznym stanom komorbidnosti [Pro-inflammatory cytokines (IL-1β, TNF-α) and oxidant-antioxidant balance in blood patients with renal v d stage chronic disease on the value of comorbidity index]. Imunolohiia ta alerholohiia: Nauka i praktyka, 2014;1:26-30. https://scholar.google.com.ua/citations?user=y0Me1tIAAAAJ&hl=ru
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