Violations in apoptosis control system in children with nephrotic syndrome

Abstract

Proteinuria is a marker of kidney damage which reflects the loss of selectivity of the filtration barrier. The objective of this paper was to study the topical features of factors controlling apoptosis activity levels in kidney tissue in children with nephrotic syndrome. 53 patients aged 10-15 years with active stage of nephrotic syndrome were included to the study. Immunohistochemical examination of proapoptotic factor Bax, antiapoptotic factor Bcl-xL levels, apoptosis evaluation in kidney biopsy specimens were done. Analysis of the level of proapoptotic factor Bax levels in kidney slices obtained from children with morphological forms of nephrotic syndrome, focal segmental glomerulosclerosis, showed the presence of high levels of Bax in both glomerular and tubular-interstitial segments. However, higher imunosignal was recorded in glomeruli with FSGS I-II st. compared to tubular segment. When complete glomerular sclerosis observed high levels of Bax are localized in the surrounding tubule and interstitial segment. Levels of antiapoptotic factor Bcl-xL levels were studied. In kidney sections a presence of a certain level Bcl-xL in both glomeruli, tubuli and interstitium was found. Higher immune signal was recorded in tubule-interstitial segment as compared to glomeruli with FSGS I-II st. When complete glomerular sclerosis occurred relatively high immune signal of Bcl-xL is localized in the surrounding tubule-interstitial segment with almost complete absence of glomeruli. The results of analysis of the level of apoptosis in sections of kidney biopsy material from children with morphological form of nephrotic syndrome focal segmental glomerulosclerosis revealed the presence of a high level of apoptotic cells. Moreover, we show that in sclerotic glomeruli with glomerulosclerosis level II-III the majority of apoptotic cells are localized in glomeruli. Quantitative analysis of apoptosis levels in kidney sections of patients with FSGS I-II st. revealed apoptotic index (AI) in glomeruli at level 22,29 ± 0,86%, in the tubule-interstitial component - 9,43 ± 0,59% (p˂0,01). With FSGS III-IV st. high AI was found in tubule-interstitial component - 29,27 ± 1,18%, in glomeruli - 4,7 ± 0,54% (p˂0,001). Thus, progression of glomerulosclerosis in studied pathology accompanied by increased activity of proapoptotic factor Bax and simultaneous reduction of antiapoptotic factor Bcl-xL. The dependence of levels of topical Bax and Bcl-xL expression on stages of FSGS indicate the step-dependent manner of glomerular and interstitial injuries development under the influence of proteinuria.