Prytkova H. Clinical and pathogenetic role of changes in the cytokine profile in the formation of preclinical signs of kidney damage in patients with early rheumatoid arthritis, the possibility of pharmacological correction

Subject of research – early rheumatoid arthritis (ERA); objective – the improvement of diagnostic and treatment of renal dysfunction in early rheumatoid arthritis based on a comprehensive assessment of the relationship of cytokine activation with markers of renal dysfunction and the renoprotective properties of various schemes of basic therapy and the newest immunobiological antirheumatic drugs; methods – general clinical examination, laboratory, instrumental (radiography, magnetic resonance imaging of joints, Doppler study of intrarenal hemodynamics), statistical methods of information processing; scientific novelty and results – new data were obtained regarding the pathogenetic relationship between the functional state of the kidneys and the activity of expression of IL-6 and TNF-ɑ in the blood, followed by the formation of renal dysfunction at ERA. Cytokine metabolism and activity of immuno-inflammatory processes have been comprehensively investigated, with determining the role of association of these processes in the development of renal hemodynamic disorders and renal functional reserve. Associative pathogenetic relationships between the severity of impaired TNF-ɑ expression and indices of renal vascular resistance have been evaluated according to renal blood flow on the base of dates of Doppler ultrasound in these patients. The usage of IL-6 level in predicting the high risk of developing renal dysfunction at ERA has been refined and clinically tested. The concept regarding the pathogenetic role of the activity of the immuno-inflammatory processes depending on the variant of the disease course in the formation of nephropathy at ERA has been formed and generalized. The presence of reliable interdependence between the degree of erosive-destructive processes and the concentration index of TNF-ɑ in patients with ERA is shown. New prognostic value for potential predictors of nephroprotective effect of treatment and development of glomerular filter porosity progression is shown. The mathematical model was constructed, which allows to reliably and correctly determine the individual probability of development of an increase in the traditional index of kidney lesion (the albumin / creatinine ratio), that will allow to develop timely personal treatment tactics and identify risk`s groups for the progression of internally glomerular hemodynamic disorders in patients with ERA to prevent formation of renal dysfunction. A comprehensive study of the state of intrarenal blood flow and the dynamics of cytokine levels (IL-6 and TNF-a) depending on the clinical features of the disease in this cohort of patients was further developed. The prognostic and clinical-diagnostic value of cytokine activation in determining the development of functional disorders of the kidneys in ERA was evaluated. It was improved comprehensive study about potential subclinical markers of nephropathy to determine the state of glomerular and tubular segments of the nephron, assessment of intraglomerular hypertension / hyperfiltration, determination of some parameters of Doppler renal blood flow at ERA. The presence of a reliable association between the severity of objective signs of erosive-destructive processes of bone and soft tissue structures of the wrist joints and carpo-metacarpal zone according to Magnetic Resonance Imaging (MRI) and the expression of some cytokines has been proved. The comparison of prognostic significance and informativeness of clinical indicators is performed and the most optimal and reliable factors that determine the formation of nephropathy in ERA are identified. For the first time by the method of logistic regression the mathematical equation of calculation of personal a priori probability of development of renal dysfunction for quantitative assessment of risk is constructed. There was optimized therapy with the appointment of genetically engineered monoclonal antibodies to interleukin-6 on the base of glucocorticoid therapy at ERA. New data on the effect of new basic therapy on the activity of the immuno-inflammatory process, the functional state of the kidneys and the parameters of bone and cartilage destruction of the joints of the hands are obtained. Principles of rational renoprotective strategy and differentiated approach in prescribing therapy with personification by definition of pathological changes in the kidneys were elaborated. The scientific idea of relevance of early appointment of biological DMARDs in combination with synthetic, renoprotective properties of various schemes of basic therapy and the newest immunobiological antirheumatic drugs is formulated and expanded; introduction – diagnostic and treatment work, educational process; scope of use – diagnosis and treatment at departments of rheumatology and therapy, educational process at the chairs of therapy of medical educational institutions.