Proteinuria is a marker of kidney damage, reflecting the loss of selectivity of the filtration barrier. Moreover, proteinuria is a determining factor in the development and progression of kidney damage due to activation of apoptosis, inflammation, fibrosis, vascular damage.

The objective of this paper was to study the topical features of factors controlling apoptosis activity levels in kidney tissue in children with chronic glomerular diseases. 23 patients aged 5–18 years with active stage of nephrotic type of chronic glomerulonephritis were included to the study. Immunohistochemical examination of proapoptotic factor Bax, antiapoptotic factor Bcl-xL levels, apoptosis evaluation on kidney biopsy specimens were done.

Analysis of the level of proapoptotic factor Bax levels in kidney slices obtained from children with morphological forms of chronic glomerulonephritis, focal segmental glomerulosclerosis with signs of inflammation, showed the presence of high levels of Bax in both glomerular and tubular-interstitial segments. Hovewer, 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 tubuli and interstitial segment.

Levels of anti-apoptotic factor Bcl-xL levels were studied. In kidney sections obtained from children with morphological forms of chronic glomerulonephritis, focal segmental glomerulosclerosis with signs of inflammation the presence of a certain level Bcl-xL in both glomeruli and tubuli interstitium was found. Higher imunosignal was recorded in tubuli, interstitial segment compared to glomeruli with FSGS I-II st. When complete glomerular sclerosis relatively high imunosignal of Bcl-xL is localized in the surrounding tubuli, interstitial segment with the 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 chronic glomerulonephritis 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 localized in the glomeruli. Quantitative analysis of apoptosis levels in kidney sections of patients with neptrotic syndrome and FSGS I-II st. revealed apoptotic index (AI) in glomeruli at level 22,29 ± 0,86 %, in the tubuli and interstitial component – 9,43 ± 0,59% (p ˂ 0,01). With FSGS III-IV st. high AI was found in tubuli, interstitial component – 29,27 ± 1,18 %, in the glomeruli – 4,7 ± 0,54 % (p ˂ 0,001).

Thus, the progression of glomerulosclerosis in the studied pathologies accompanied by increased activity of proapoptotic factor Bax and simultaneous reduction of anti-apoptotic factor Bcl-cxL. 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.

The differences between levels of the damages and their correlation in patients with FSHS resulting from nephrotic syndrome and IgA nephropathy indicates direct dependence of glomerular and tubular damage on the level and type of proteinuria. Further study of the molecular mechanisms of apoptosis in proteinuric kidney disease in children and approaches development to their correction is a promising direction in terms of preventing and slowing down the kidney damage development.

Ключові слова: nephrotic syndrome, glomerulosclerosis, apoptosis, Bax, Bcl-xL, immunostaining

Повний текст: PDF (Ukr)

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