Vakulenko L. Diagnosis, prevention and prognosis of systemic and regional hemodynamics disorders in children with chronic pyelonephritis.

The dissertation systemically presents a new solution to the research and practical problem - improvement of diagnostic tactics and personalized measures of cardiovascular disorders correction at different stages of clinical monitoring in children with chronic pyelonephritis. The clinical features of chronic kidney disease progression and cardiovascular complications formation have been theoretically generalized. The concept of the pathological process development has been formulated, the clinical and pathogenetic patterns as well as structural and functional changes of the kidney and heart have been revealed. The prognostic value of determined clinical-ultrasonographic, Doppler-ultrasonographic parameters and indicators of 24-hour ambulatory blood pressure monitoring, endothelial dysfunction and status of the autonomic nervous system provides an opportunity to recommend them as auxiliary criteria in assessing the severity of cardiovascular system functional state disorders in children with chronic pyelonephritis. The diagnostic value of the available non-invasive technique for the kidney stiffness assessment with ultrasound has been proved which can be recommended for the implementation in health care for routine evaluation of the renal inflammatory process severity and fibrosis formation. It has been revealed that in children with chronic pyelonephritis, disorders of systemic and renal hemodynamics are strongly intercorrelated. It has been demonstrated that blood velocity and peripheral vascular resistance indices, pulsation index and systolic-diastolic ratio at the level of the main and segmental renal arteries are highly informative prognostic indicators characterizing the state of renal hemodynamics in children with chronic pyelonephritis. The risk factors for developing systemic and renal hemodynamics disorders associated with the etiological factor related to chronic pyelonephritis in children have been identified. The main risk factors for an unfavorable course of chronic pyelonephritis in children are anomalies of the urinary tract, a prolonged initial episode of pyelonephritis, arterial hypertension, anemia at the disease onset, functional disorders of urodynamics, concomitant persistent infection, metabolic disorders, dysembryogenic stigmas. Understanding of the cardiovascular disorders and renal arterial hypertension mechanisms in children with chronic pyelonephritis has been enlarged. It has been proved that renal hemodynamics disorders are induced by vasoconstrictor reactions of the renal blood flow, which are characterized by an increase in the peripheral vascular resistance, maximum blood flow velocity and systolic-diastolic ratio, and subsequent progression to vasodilatory changes with a decrease in all the above-mentioned indicators. Based on the work results, two predictive models have been developed. The first model is the prognostic table for developing chronic pyelonephritis and the second one is a mathematical model for predicting the cardiovascular complications development - left ventricular hypertrophy and arterial hypertension in children with chronic pyelonephritis. The use of the proposed mathematical model for the development of cardiovascular disorders in children with chronic pyelonephritis will identify the group at increased risk of cardiovascular complications, which need to be timely corrected. The revealed hemodynamic disorders required timely nephroprotective therapy administration. Enalapril (iACE) add-on therapy was accompanied by positive dynamics in 75.2% of patients. In the treatment follow-up, the changes primarily occurred at the segmental renal artery level, which was manifested in the velocity indicators normalization and the resistance indices reduction. In the treatment course, there was a significant decrease in the frequency and severity of arterial hypertension syndrome from 34.0% to 6.9% (p <0.05). The mean blood pressure continued to decrease over the 3-year study period, reaching the target level in 79.6% of patients with chronic pyelonephritis. This dynamics is an important independent predictor for retarding progression of kidney disease. L-arginine combined with enalapril add-on treatment resulted in positive changes in 47.8% of patients due to a significant increase in the brachial artery diameter and brachial flow-mediated dilation as well as a decrease in the blood velocity parameters. A significant increase in the normoergic variant of the response to a test with endothelium-dependent vasodilation and a decrease in the number of pathological variants were recorded. For the treatment of chronic pyelonephritis patients with cardiovascular disorders manifestations, it is recommended to use a differential approach. Enalapril (iACE) as monotherapy is recommended for patients with stage I chronic kidney disease and combined therapy with enalapril and L-arginine - for patients with stage II-III chronic kidney disease.