METHODOLOGICAL APPROACHES TO EARLY DETECTION OF TOXIC ACUTE KIDNEY INJURY BASED ON DYNAMICS OF SOME BIOMARKERS

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Abstract

The article presents the results of the experimental toxicological study of rats poisoned with uranyl acetate dihydrate (300 mg / kg body weight). The aim of this study was to develop methodological approaches to the early detection of acute toxic kidney damage on the basis of the dynamics of some biomarkers on 1, 3 and 7 days after nephrotoxin administration. For renal biomarkers reflecting the value of glomerular filtration rate (creatinine in the blood, cutoff 112,77 µmol/l) the mechanism of cell death (TPA in urine, cutoff of 5.28 IU/ml), degenerative changes and regeneration (KIM-1 in urine, cutoff of 0.28 ng/ml; at values above 8,2 ng/ml the lethal effect can be expected), the inflammatory infiltration and the induction of tissue reparation (MCP-1 in urine, cutoff 11,70 pg/ml, TGF-β1 in the urine, cutoff 34,33 pg/ml), the sensitivity and specificity have been determined. According to the sequence of urine level increase, the studied biomarkers can be arranged in the following series: early stage – TPA; stage of necrosis growth and leukocyte infiltration – KIM-1, MCP-1, creatinine; stage of deep necrotic changes – TGF-β1. The studied markers are of interest for use as diagnostic tools in determining the stage of kidney disease in nephrotoxic poisoning.

About the authors

K. V. Sivak

A.A. Smorodintsev Research Institute of Influenza, RF Ministry of Healthcare, 197376, Saint Petersburg

Author for correspondence.
Email: kvsivak@gmail.com
Сивак Константин Владимирович (Sivak Konstantin Vladimirovich), кандидат биологических наук, заведующий отделом доклинических исследований Russian Federation

T. N. Savateeva-Lyubimova

A.A. Smorodintsev Research Institute of Influenza, RF Ministry of Healthcare, 197376, Saint Petersburg

Email: drugs_safety@mail.ru
Саватеева-Любимова Татьяна Николаевна (Savateeva-Lyubimova Tatiana Nikolaevna), доктор медицинских наук, профессор, ведущий научный сотрудник лаборатории безопасности лекарственных средств Russian Federation

T. A. Gus’kova

M.V. Dorogov Yaroslavl Center for the Transfer of Pharmaceutical Technologies, K.D. Ushinsky Yaroslavl State Pedagogical University, 150010, Yaroslavl

Email: tagus@rambler.ru
Гуськова Татьяна Анатольевна (Gus’kova Tatyana Anatolevna), заслуженный деятель науки РФ, член-корреспондент РАН, доктор медицинских наук, профессор, заместитель Председателя Всероссийской общественной организации токсикологов, ведущий научный сотрудник отдела доклинических исследований Russian Federation

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Copyright (c) 2019 Sivak K.V., Savateeva-Lyubimova T.N., Gus’kova T.A.


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