Burlaka E. Apoptosis-dependent mechanisms of kidney damage in proteinuric diseases in children: a clinical and experimental study

The dissertation is devoted to solving the problem of increasing the effectiveness of diagnostic and therapeutic measures in children with diseases associated with the persistent effect of proteinuria (nephrotic syndrome, diabetic nephropathy) by studying the markers of the apoptosis control system on experimental models and their evaluation in the clinic. The study design includes an in vitro, in vivo, clinical study. 112 children with nephrotic syndrome who were receiving inpatient treatment in the Department of Pediatric Nephrology of Children's Clinical Hospital № 7 in Kyiv and 113 children with type I diabetes with/without diagnosed diabetic nephropathy of the I-II stage who were receiving inpatient treatment in Department of Endocrinology, Children's Clinical Hospital № 6, Kyiv. The control group included 145 children of the appropriate age and gender. The scientific novelty of the study is that molecular biomarkers and mechanisms of apoptosis-dependent kidney damage were investigated for the first time at the experimental and clinical levels. On the model of hemolytic-uremic syndrome in vitro, the experimental model of nephrotic syndrome in vivo (Heymann passive nephritis), it was shown for the first time that apoptosis occurs as a result of the balance in the Bax/Bcl-xL factor system. The protective antiapoptotic effect of the endogenous steroid hormone ouabain in these models is realized due to the restoration of Bax/Bcl-xL imbalance. The mechanisms of apoptosis development, background conditions that increase it, and accompanying metabolic disorders in children with nephrotic syndrome and diabetic nephropathy were studied. An algorithm for the approach to the formation of classification clinical forms of activity in children with nephrotic syndrome and risk groups in children with type I diabetes with/without diagnosed diabetic nephropathy has been developed. The effectiveness of the improved scheme of therapy of the steroid-sensitive form of nephrotic syndrome in children with clinical forms that correspond to the I and II degree of activity, and the scheme of therapeutic correction in children with type I diabetes mellitus, diagnosed with a form of diabetic nephropathy of the I-II stage, has been substantiated and proven.