In the Thesis, from the perspective of a systematic approach, the author represents a new solution to such a scientific and practical issue as improvement of the diagnostic tactics and personalized measures aimed at correction of metabolic disorders and early renoprotection in children with chronic kidney disease.
The author has made a theoretical generalization of the study into the peculiarities of chronic kidney disease progression, created the concept of pathological process development, and identified the clinical and pathogenetic patterns of occurrence, course and progression of nephrosclerosis.
A strategy has been developed for the prevention and control of the course of chronic kidney disease in children which involves identification of risk groups, clarification of the potential goals of intervention and creation of a personalized early renoprotection program to inhibit nephrosclerosis progression and delay the need for renal replacement therapy.
The author has also adapted the updated classification of chronic kidney disease in children to bring it in compliance with the national conditions resting upon the evidence base obtained, with a view to determining the stages and substages of chronic kidney disease in children and determining the diagnostically significant values of serum cystatin C concentration and the estimated glomerular filtration rate based on cystatin C.
The author has substantiated and proved the expediency of using cystatin C in blood serum (sensitivity 73%, specificity 91%) and the estimated glomerular filtration rate formulas based on cystatin C using the equations by M. Zappitelli, Cystatin C-based equation (2012) Pediatric GFR Calculator –NKF, FJHoek, as a combined tool designated for adequate assessment of the functional condition of kidneys, for determination and delineation of the stages and substages of chronic kidney disease stages 1-3 (3a and 3b) in children, and for identification of the categories of patients with prognostically unfavorable forms of renal pathology, such as bilateral ureterohydronephrosis, polycystic kidney disease, and chronic tubulointerstitial nephritis as a result of acute kidney injury.
The author has worked out the concept of development of metabolic disorders as a leading pathogenetic link which severity determines the level of kidney functional condition and the likelihood of nephrosclerosis progression.
The thesis elaborates on the ideas about pathogenetic mechanisms of nephrosclerosis formation, determination of the role of the metabolomic amino acid profile, carnitine status, determination of candidate markers reflecting the progressive course of nephrosclerosis, for the purpose of individualized prescription of metabolic and dietary nutritional therapy to children with chronic kidney disease.
Significant metabolic predictors of chronic kidney disease progression in children have been found: amino acids - arginine, citrulline, 5-oxoproline; acylcarnitines - C5DC (glutarylcarnitine), C6DC (3-methylglutaconylcarnitine).
The author demonstrates the efficiency of an individualized approach to the correction of metabolic disorders using levocarnitine and dietary nutritional therapy in children with chronic kidney disease.
Owing to the proposed differentiated approaches to renoprotection, chronic kidney disease progression was slowed down in 91,5% of children with stage 1, in 78,2% with stage 2 and 35% with stage 3 (3a and 3b).
