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Introduction: Acute kidney injury is a widespread complication in hospitalized patients, with a high mortality rate and long-term complications affecting prognosis and quality of life and with high human and financial costs. In addition, to date, no clear algorithm for the prevention of this type of damage has been developed. Materials and methods: The research was carried out on male Wistar rats. A 40-minute renal ischemia-reperfusion model was used to model acute kidney injury. Further, the renoprotective properties of carbamylated darbepoetin, udenafil and their combination were assessed based on the analysis of the biochemical studies’ results, dynamics of the renal status and the renal microvasculature, and the pathomorphological picture. A series of experiments was also carried out to assess the contribution of adenosine triphosphate-dependent potassium channels and nuclear factor kappa B to the renoprotective properties of the said agents. Results and discussion: Prophylactic administration of carbamylated darbepoetin at a dose of 50 µg/kg and udenafil at a dose of 8.7 mg/kg led to a statistically significant decrease in creatinine and blood urea nitrogen, an increase in glomerular filtration rate with a simultaneous decrease in fractional excretion of sodium, as well as an increase in the level of microcirculation in the kidneys and a decrease in the severity of damage according to the data of a pathomorphological examination at all time points of the experiment. A higher efficiency of correcting ischemic and reperfusion renal injuries was observed when using a combination of the said pharmacological agents. A series of experiments with glibenclamide demonstrated that its preliminary administration levels the renoprotective properties of carbamylated darbepoetin and udenafil. The ability of the studied pharmacological agents to reduce lipopolysaccharide-induced expression of nuclear factor kappa B in mononuclear cells was also demonstrated. The results of the research suggest that the renoprotective effects of carbamylated darbepoetin, udenafil, and their combination are realized through ATP-dependent potassium channels and nuclear factor kappa B. Conclusion: Pharmacological preconditioning with carbamylated darbepoetin and udenafil reduces the severity of acute kidney injury induced by ischemia-reperfusion. Graphical abstract:

Aim.The research was designed to study the renoprotective properties of erythropoietin derivatives on the kidney ischemiareperfusion experimental model.Materials and methods.The renoprotective properties of asialo erythropoietin (0.4 μg/kg and 2.4 μg/kg 30 minutes before the induction of ischemia) and carbamylated darbepoetin (50 μg/kg 24 hours before the ischemic stimulus) were studied in comparison with erythropoietin and darbepoetin in a series of experiments on male Wistar rats on a 40-minute bilateral model of renal ischemia-reperfusion. The renoprotective properties were evaluated by the results of biochemical markers of acute kidney injury, the dynamics of glomerular filtration rate and fractional sodium excretion, as well as the severity of microcirculatory disorders.Results.It was found that the prophylactic use of asialo erythropoietin (dose-dependent) and carbamylated darbepoetin leads to a decrease in the serum concentration of markers of acute renal damage, an increase in the glomerular filtration rate, a decrease in fractional sodium excretion, and a decrease in microcirculatory disorders.Conclusion.Asialo erythropoietin and carbamylated darbepoetin have the pronounced renoprotective properties and are the promising agents for the prevention and treatment of acute kidney injury.

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2ФГАОУ ВО «Белгородский государственный национальный исследовательский университет» Минобрнауки РФ; Белгород, Россия В работе представлены результаты исследования нарушений функции эндотелия, возникающих при моделировании «тепловой ишемии» почки и возможности их коррекции дистантным ишемическими и фармакологическим прекондиционированием. Моделирование «тепловой ишемии» почки характеризуется нарушением микроциркуляции и экспрессией eNOS в ткани почек. Применение дистантного ишемического прекондиционирования и ингибиторов фосфодиэстеразы 5 типа силденафила и тадалафила приводит к выраженной коррекции нарушений микроциркуляции и активности eNOS. При моделировании «тепловой ишемии» почки на фоне дисфункции эндотелия вызванной ADMA-подобным L-NAME индуцированным дефицитом оксида азота наблюдаются более выраженные нарушения микроциркуляции и активности eNOS. Применение дистантного ишемического и фармакологического прекондиционирования ингибиторами фосфодиэстеразы 5 типа при данном типе патологии приводило к выраженной коррекции нарушений микроциркуляции и активности eNOS. Введение блокатора АТФ-зависимых К + каналов глибенкламида при коррекции дистантным ишемическим и фармакологическим прекондиционированием нарушений, вызванных моделированием «тепловой ишемии» почки, приводит к снижению их эффективности.Ключевые слова: тепловая ишемия; микроциркуляция почки; прекондиционирование; реперфузия; ингибиторы фосфодиэстеразы 5 типа Раскрытие информации: Исследование не имело спонсорской поддержки. Авторы заявляют об отсутствии конфликта интересов.