DEVELOPMENT DEGREE AND THE ROLE OF ENDOTHELIAL DYSFUNCTION IN THE DEVELOPMENT AND PROGRESSION OF NON-ALCOHOL FATTY LIVER DISEASE AND CHRONIC KIDNEY DISEASE IN PATIENTS WITH OBESITY

O. S. Khukhlina; A. A. Antoniv; Z. Ya. Kotsiubiichuk; V. S. Gaidychuk; O. V. Andrusyak

O. S. Khukhlina Higher Educational Establishment of Ukraine “Bukovinian State Medical University”, 10 Teatralna Square, Chernivtsi, 58002 Ukraine
A. A. Antoniv Higher Educational Establishment of Ukraine “Bukovinian State Medical University”, 10 Teatralna Square, Chernivtsi, 58002 Ukraine
Z. Ya. Kotsiubiichuk Higher Educational Establishment of Ukraine “Bukovinian State Medical University”, 10 Teatralna Square, Chernivtsi, 58002 Ukraine
V. S. Gaidychuk Higher Educational Establishment of Ukraine “Bukovinian State Medical University”, 10 Teatralna Square, Chernivtsi, 58002 Ukraine
O. V. Andrusyak Higher Educational Establishment of Ukraine “Bukovinian State Medical University”, 10 Teatralna Square, Chernivtsi, 58002 Ukraine

Keywords: chronic kidney disease, non-alcoholic fatty liver disease, obesity, endothelial dysfunction

Abstract

Introduction. The increase in the frequency of non-alcoholic fatty liver disease (NAFLD) on the background of obesity and chronic kidney disease (CKD) cases in people of working age in Ukraine and in the world necessitates the research on mechanisms of mutual burden and finding new factors for the progression pathogenesis of this comorbidity.

The aim of the study. Determine the degree of development and the role of endothelial dysfunction in the development and progression of non-alcohol fatty liver disease and chronic kidney disease in patients with obesity.

Material and methods of research. 354 patients with NAFLD were examined: 84 of them had NAFLD with obesity stage I (1-st group), which contained 2 subgroups: 32 patients with NAS and 52 patients with NASH; 270 patients with NAFLD with comorbid obesity stage II and CKD stage І-ІІІ (2-nd group), including 110 patients with NAS and 160 patients with NASH, who were having inpatient treatment in 2014-2018 at the therapeutic departments 1 and 2, gastroenterology departments of Chernivtsi Regional Municipal Establishment "Hospital of Emergency Medical Aid - University Hospital", which is the clinical base of the Department of Internal Medicine, Clinical Pharmacology and Occupational Diseases. The control group consisted of 90 patients with CKD of stage І-ІІІ with normal body mass (3-rd group) and 30 practically healthy persons (PHPs).

Research results. As a result of the study related to the features of the functional endothelium for the comorbidity of chronic kidney disease (CKD): chronic pyelonephritis with obesity and non-alcoholic fatty liver disease (NAFLD) depending on its form and the stage of CKD increased endothelium dysfunction which occurs as a result of metabolic intoxication ( hyperlipidemia, postprandial hyperglycemia, increase in the degree of IP, hyperleptinemia, deficiency of adiponectin, increase of oxidative and nitrositive ( hyperactivation іNOS ) stress, and reduces the endothelium-dependent vasodilatation of the branchial artery, deficiency and synthesis of liberation of nitrogen monoxide (endothelium-relaxant factor) due to the shortage of endothelial NO-synthase.

Conclusions: The established endothelium dysfunction is an essential pathogenetic factor and inducer of NAFLD and CKD progression on the background of obesity. Endothelium dysfunction progresses due to the transformation of nonalcoholic steatosis into steatohepatitis, with combining NAFLD with CKD, progressing with CKD stage, degree of insulin resistance, leptin resistance, intensity of oxidative and nitrositive stress, lipid distress syndrome.

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References

1 Athyros V, Tziomalos K, Katsiki N et al. [Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease; an update.]. World J. Gastroenterol. 2015. 21: 6820–6834

2 Chang Y, Ryu S, Sung E, et al. [Nonalcoholic fatty liver disease predicts chronic kidney disease in nonhypertensive and nondiabetic Korean men.] Metabolism. 2008. 57: 569–576.

3 Iх JH, Sharma К. [Mechanisms Linking Obesity, Chronic Kidney Disease, and Fatty Liver Disease: The Roles of Fetuin-A, Adiponectin, and AMPK.] J. Am. Soc. Nephrol. 2010. Mar; 21(3): 406–412.

4 Franchini S, Savino A, Marcovecchio ML. et al. [The effect of obesity and type 1 diabetes on renal function in children and adolescents.] Pediatr. Diabetes. 2015, 16: 427–433.

5 KDIGO 2012[Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease.] Kidney International Supplement 2013;3:1–150.

6 Levey AS, Stevens LA, Schmid CH, et al. [A new equation to estimate glomerular filtration rate.] Ann Intern Med. 2009;150(9):604-12.

7 Machado MV, Gonçalves S, Carepa F, et al. [Impaired renal function in morbid obese patients with nonalcoholic fatty liver disease.] Liver Int. 2012. Feb; 32(2): 241-248.

8 Marcuccilli M, Choncho M. [NAFLD and Chronic Kidney Disease]. Int. J. Mol. Sci. 2016. Apr; 17(4): 562.

9 Musso G, Cassader M, Cohney S, et al. [Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities.] Diabetes Care. 2016. Oct; 39(10): 1830-1845.

10 Papademetriou M, Athyros VG, Geladari E, et al. [The Co-Existence of NASH and Chronic Kidney Disease Boosts Cardiovascular Risk: Are there any Common Therapeutic Options?] Current Vascular Pharmacology, 2017;15:1-15.