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"Kidneys" 3 (13) 2015

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Renal morphological changes in experimental systemic vasculitis: relation to nephrotoxic microelements

Authors: T.B.Bevzenko

Categories: Nephrology

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systemic vasculitis, experiment, animals, kidneys, morphology, nephrotoxic microelements.

Introduction. There is a relation the prevalence of systemic vasculitis (SV) with the degree of contamination by toxic microelements (ME) in the regions residing of people, which also increases the rate of progression of any chronic kidney disease. The aim of this study was to evaluate the morphological character of the individual renal structures lesion under increased exogenous influence of nephrotoxic ME (cadmium - Cd, Lithium - Li, molybdenum - Mo) in animals with experimental SV.

Material and methods. The experiment was performed on 49 animals (nonlinear male rats weighing about 250 g), divided into two groups - the control group (24 individuals) and the main one - 25. Another control group consisted of 10 intact rats. SV with renal lesion was modeled by administration Freund's complete adjuvant with solution of lyophilized aqueous saline extract of renal cortex and splenic deoxyribonucleic acid of cattle into the root of the tail of rats and intraperitoneal administration of sodium azide. Rats of control group with model of SV were on normal feeding, and sulfate Cd, Li oxybutyrate and ammonium molybdate were added in daily food of animals of the main group. Modelling of the disease was performed within one month, and then rats were taken out of the experiment under ether anesthesia and intra-abdominal injection of Nembutal. Histological sections of renal preparations were stained with hematoxylin-eosin, Alcian blue and Van Gieson, PAS-reaction was performed. The lesions of distinct renal structures (glomeruli, tubules, stroma and vessels) were scored (from 0 to 3 points). The average lesion was calculated by the formula: (a + 2b + 3c): (a + b + c + d), where a, b, c - number of animals with 1, 2 and 3 points accordingly, and d - number of rats with absence of this sign.

Results. Thrombuses and areas of hemorrhages were observed in the vessels of animals with SV. Histological changes in the skin and the lungs were characterized by a combination of necrotizing granuloma, vasculitis of small and medium-sized vessels with extensive interstitial and perivascular infiltrates. Granuloma was characterized by the appearance of necrotic zone surrounded by epithelioid histiocytes. The changes in the walls of small arteries and veins were manifested with the presence of cellular infiltration of giant cells and cicatricial sclerotic changes in the vessels. Among all rats with model of SV the proliferation of mezangial cells was found in 59% of cases, increased mesangial matrix - 80%, thickening of the basement membrane of Shumlansky – Bowman's capsule - 16%, proliferation of capillary endothelium of the glomeruli - 86%, glomerular sclerosis / hyalinosis - 63% proliferation of arteriolar endothelium - 65%, dystrophy, atrophy of tubules - 98%, cellular (mainly lymphohistiocytic) infiltration of stroma - 84% sclerosis of stroma - 74%. According to multivariate dispersion analysis the character of feeding affects integral morphological characteristics of the pathological process. Completion of the univariate analysis indicates a relationship of frequency of increased mesangial matrix and dystrophy / atrophy of the renal tubules with the model of the disease. The frequency of thickening of Shumlansky – Bowman's capsule in animals of the main group was met 6,7 times more often than in the control one, and the proliferation of arteriolar endothelium – 1,6 times. The average parameters of proliferation of arteriolar endothelium in animals of the main group were 63% statistically significantly higher than in control one, and tubular dystrophy - 21%.

Thus, the nephrotoxic effects of Cd, Li and Mo on the animals manifested as an adverse influence of these ME to the thickening of the basement membrane of Shumlansky – Bowman's capsule, the proliferation of endothelium of arterioles and dystrophic changes of tubules. Cadmium intoxication causes the induction of apoptosis of renal cells, and urinary excretion of Cd is directly related to the parameters of proteinuria, and the level of this ME is a marker that reflects early renal dysfunction.

Conclusions. The experiment on rats showed that exogenous dietary exposure  of such nephrotoxic ME as Cd, Li and Mo on an animal organism with a model of SV, has an adverse impact on the integral morphological parameters of lesion of renal structures. High receipt of Cd, Li and Mo in an organism increases frequency of damage of the basement membrane of Shumlansky – Bowman's capsule about 7 times, increases the severity of proliferation of arteriolar endothelium by 2/3 and dystrophic and atrophic changes of the tubules - by 1/5. The obtained experimental data will be useful for hygienic, diagnostic and therapeutic measures in patients with SV with renal lesion, living in different ecological regions by levels of environmental Cd, Li, and Mo.


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