Features of the Functional State of the L-arginine / NO-synthase / Arginase System and Oxidative Processes in Patients with end-stage Renal Disease due to Chronic Glomerulonephritis Before and After a Hemodialysis Session

Abstract

Introduction. Recently, much attention has been paid to the study of the relationship between chronic kidney disease (CKD) and the occurrence of various complications, which are accompanied by changes in the L-arginine / NO-synthase / arginase system and oxidative stress. In chronic renal failure (CRF), activation of lipid peroxidation (LPO) and disorders in the L-arginine / NO-synthase / arginase system are integrated into the mechanisms of endothelial dysfunction, hypertension, increased circulating cytokine content in the blood, dysfunction. The aim of the study. To find out the features of the functional state of the L-arginine / NO-synthase / arginase system and oxidative processes in patients with end-stage renal disease due to chronic glomerulonephritis before and after a hemodialysis session. Materials and methods. After obtaining written consent the survey agreed by the Ethics Commission of Danylo Halytsky Lviv National Medical University (LNMU) in accordance with the principles of the Helsinki Declaration of Human Rights, the Council of Europe Convention on Human Rights and Biomedicine, relevant laws of Ukraine and international acts was conducted in the Municipal Non-Profit Enterprise (MCP) of the Lviv Regional Council (ENT) “Lviv Regional Clinical Hospital”. In a randomized manner with preliminary stratification by the presence of CKD (chronic glomerulonephritis) with terminal CRF diagnosed according to the Order of the Ministry of Health of Ukraine. 280/44 of 11.05.2011 (On approval of the standard and unified clinical protocols for medical care in the specialty “Nephrology”) and Recommendations for improving the quality of diagnosis and treatment of kidney disease (2002) – Kidney Disease Outcomes Quality Initiative (KDOQI) and 2012 – Kidney Disease: Improving Global Out comes (KDIGO), treated with hemodialysis (HD) (3 times a week for four hours using synthetic dialyzers and bicarbonate buffer), 42 patients (22 women (52.38 %), 20 men), 62,00 %), whose average age was 56 years) were involved to the study. The control group (CG) consisted of 20 relatively healthy, comparable in gender and age volunteers. Results. The content of L-arginine in the patients with terminal CRF, was reduced (by 33.0 % (p less than 0.01) and 31.0 % (p less than 0.01), respectively) compared with the reference values of CG. After the HD session, the content of L-arginine in blood plasma decreased by 20.0 %, in lymphocyte lysate – by 30.0 % (p less than 0.05) compared with patients before the HD session. Before the HD session, the content of H2S in blood plasma decreased by 23.0 % (p less than 0.01), the content of H2S in lysate did not differ significantly from that in CG of donors and its content in blood plasma. After the HD session, its content in blood plasma decreased by 12.0 % (p less than 0.05), in lymphocyte lysate – by 23.0 % (p less than 0.05). The plasma concentration of asymmetric dimethylarginine (ADMA) was 2.3 times higher (p less than 0.01), and the concentration of symmetric dimethylarginine (SDMA) was 3.4 times (p less than 0.01) than in the blood of donors. After the HD session, plasma ADMA and SDMA concentrations decreased by 49.0 % (p less than 0.05) and 48.0 % (p less than 0.05), respectively. The activity of iNOS increased 15-fold (p less than 0.01), and eNOS activity decreased by 70.0 % (p less than 0.05). After the HD session, iNOS activity increased (14 times, p less than 0.01) as well as eNOS activity (8 times, p less than 0.01). Plasma arginase activity was 33.0 % higher than in the CG. The arginase activity in lymphocytes was incredibly lower (by 14.0 %, p more than 0.05) before the HD session, compared with the CG, arginase activity after the HD session tended to increase. The content of thiobarbituric acid (TBA)-active products in plasma prior to the HD session, was higher by 34.0 % (p less than 0.05), oxidized low-density lipoprotein (oxLDL) content and myeloperoxidase activity did not change. After the HD session, the content of TBA-active products in blood plasma decreased by 14.0 % (p less than 0.05), myeloperoxidase activity was below the normal values. The activity of superoxide dismutase (SOD), catalase and glutathione peroxidase prior to the HD session, did not differ significantly compared with the CG. After the HD session, catalase activity was significantly reduced (p less than 0.05) compared with controls. Vitamin C, its total and oxidized forms, decreased by 45.0 % (p less than 0.05) and 19.0 % (p less than 0.05), respectively, compared with the CG. After the HD session, the concentration of vitamin C in total decreased by 27.0 % (p less than 0.05), oxidized form – by 25.0 % (p less than 0.05), compared with the indicators before the HD session. The content of TBA-active products in the lysate of lymphocytes in patients with CRF, increased by 23.0 % (p less than 0.05). Comparing the changes of the TBA-active products content in blood plasma and lymphocyte lysate in patients with CRF, it should be noted that the content of TBA-active products in lymphocytes increased slightly (by 23.0 %), while in blood plasma by 33.0 % (p less than 0.05), however, the content of TBA-active products in the blood plasma was 3.4 times higher than in lymphocytes. The content of TBA-active products after HD in lymphocytes decreased by 22.0 % (p less than 0.05) and in blood plasma – by 15.0 % (p less than 0.05). The activity of SOD and catalase in the lymphocyte lysate in patients with CRF was lower (by 19.0 and 44.0 %, p less than 0.05, respectively) compared with the control group, the activity of glutathione peroxidase did not change significantly. It should be noted that the activity of SOD and catalase before HD in blood plasma was higher than in lymphocytes (p less than 0.05). The activity of SOD and glutathione peroxidase in the lymphocyte lysate after the HD session, did not change significantly in comparison with the indicators before the HD session, the catalase activity tended to decrease. Conclusions. A hemodialysis session in patients with chronic renal failure causes sharp decrease of the iNOS and eNOS activity, decrease of the content of thiobarbituric acid-active products, L-arginine and nitrite anion in the lymphocyte lysate.