Vasylchenko V. S. Protein factors of the formation of the oxidative status in chronic kidney disease. – Qualification of scientific work on the rights of the manuscript.
The dissertation for the scientific degree of Doctor of Philosophy, speciality 091 – Biology. – National University of Kyiv-Mohyla Academy, 2023.
The dissertation is devoted to the study of the oxidative status, and features of its changes, in chronic kidney disease. The first stages of chronic kidney disease do not usually have specific symptoms, which makes them difficult to identify and observe. Traditional markers of kidney dysfunction, such as plasma and urine creatinine and urea, can be within the normal physiological range, despite deterioration in renal function and therefore are not sensitive enough. The set of pathological changes in chronic kidney disease can be tentatively divided into three categories: dyslipidemia, proteinuria, and uremia. It is important to note that there is a relationship between all these components and they can influence each other. The change in oxidative status markers during chronic kidney disease has not been characterized and would provide additional information about the interrelationship between components of the pro- and antioxidant systems, and the influence of other factors on them. Deepening the understanding of redox processes and mechanisms of development of chronic kidney disease due to the detection of oxidative status can contribute to improving not only early diagnosis but also monitoring of patients with existing kidney pathologies.
This research work aimed to identify key proteins involved in the change of oxidative status in chronic kidney disease.
The following methods were used to achieve the goal: analysis and systematization of literary, scientific, methodical and other sources on the researched topic; biochemical research methods; and statistical processing of results and mathematical modelling.
Venous blood samples for the study of protein factors of oxidative status were taken from 417 patients (214 women and 203 men, aged – 18-55 years) with chronic kidney disease of stage I-V (glomerulonephritis).
All patients without acute concomitant pathologies (n=250) were divided into three groups: 1st group was formed by patients with chronic kidney disease of the I- II stages (n=53); second group was consisted of patients with chronic kidney disease of III-IV stages (n=25); third group was formed by patients with stage V chronic kidney disease (n=150). The control group consisted of 29 healthy people of the same age with a similar gender ratio. All participants gave informed consent for their participation in the study. The Bioethics Committee approved the research protocol (No. 7 dated 08/30/2016) of the Institute of Nephrology of NAMNU, and the research protocols identical to the dissertation project (No. 6 dated 06/10/2021 and No. 3 dated 19/03/2023) was approved by the Scientific Research Ethics Committee of the National University of Kyiv-Mohyla Academy.
More specifically, my PhD thesis demonstrates new data showing significant increases in activity of the enzymes that induce oxidative stress; myeloperoxidase, and elastase. In addition, there was a significant increase in the quantity of uremic toxins; indoxyl sulfate, oxalic acid, and citrulline and a decrease in the activity of the antioxidant enzyme, paraoxonase-1 from the first stages of chronic kidney disease. For the first time, the ratio between pro- and antioxidant enzymes was calculated and a thorough correlation analysis was performed between potential and
traditional markers of chronic kidney disease.
My new data provides information on potential markers of chronic kidney disease (citrulline, indoxyl sulphate, paraoxonase-1, myeloperoxidase and elastase). For the first time, the interdependence between them was analysed and demonstrated, which makes it possible to identify non-invasive markers, citrulline and indoxyl sulphate, of the early stages of chronic kidney disease.
In conclusion, analysis of markers of oxidative status makes it possible to confirm disease progression using non-invasive markers to allow early diagnosis of chronic kidney disease.
Keywords: oxidative stress, kidneys, chronic kidney disease, prooxidant- antioxidant balance, imbalance, functional capacity, stability, oxidative modification of proteins and lipids, lipid peroxidation, resistance, antioxidant system, citrulline, myeloperoxidase, chamber systems method, mathematical modelling.
