According to the World Health Organization, pathologies associated with ischemia/reperfusion occupy the leading position in the structure of mortality. The efficiency of localized kidney cancer surgery is limited by the damaging effects of prolonged warm ischemia and reperfusion. Ischemia/reperfusion damage to renal tissue may be related to changes in the expression profiles of pro- and antiapoptotic genes. Here, we have presented the longitudinal expression profiles of apoptosis-related genes in tissues of left and right (intact) kidneys of male rats exposed to unilateral ischemia followed by reperfusion. The profiles have been assessed at time points of 1, 3, and 48 h after the ischemic/reperfusion exposure by RT-qPCR quantification of mRNAs encoded by 13 genes, including BAX, p53, AIFM1, APAF1, CASP8, CASP3, CASP9,CASP7, MDM2, BCL2, CIAP1, XIAP, and ICAD, after normalization with respect to a reference gene ACTB. The study revealed a shift in the expression of pro- and antiapoptotic genes toward the predominance of proapoptotic processes, as was evinced by the increase in expression detected for the BAX, p53, AIFM1, APAF1, and CASP8 genes. One hour after the reperfusion, activation of mitochondrial, or intrinsic apoptosis was detected, while р53-dependent and extrinsic, i.e., receptor-driven, apoptosis joined at later time points. Changes in the level of expression of caspase 7 (CASP7)-encoding mRNA have only been detected 48 h after the restoration of blood flow. Changes have been observed in the transcription of pro- and antiapoptotic genes in tissues of both kidneys, which suggests the involvement of the contralateral kidney in systemic pathological process that develops during unilateral ischemia/reperfusion.

Цель исследования-изучить влияние эпидуральной блокады на функциональное состояние почек у больных локализованным раком при поведении резекции почки в условиях тепловой ишемии. Материал и методы. Обследовали 45 больных (25 мужчин и 20 женщин) локализованным раком почки T 1 N 0 M 0 в возрасте 56,5±8,7 года. Всем больным выполнили резекцию почки в условиях тепловой ишемии (15-20 минут). Больных разделили на 2 группы: основную (25 человек), в которой в периоперационном периоде применяли эпидуральную блокаду, и контрольную (20 пациентов)-без эпидуральной блокады. В крови и моче методом ИФА исследовали-цистатин С, L-FABP, КИМ-1 , ИЛ-18, а также СКФ. Обследование проводили за 1 час до операции, через 20 минут после этапа тепловой ишемии, в 1-е и 3-и сутки. По исходной концентрации цистатина С в крови больные каждой группы были разделены на 2 подгруппы: 1-концентрация цистатина С 1000 нг/мл и ниже, 2-выше 1000 нг/мл. Статистическую обработку результатов проводили с использованием пакета программ «Statistiсa 6.0» по t-критерию Стъюдента для 2-х независимых выборок. Различия считали статистически значимыми при p<0,05. Результаты. Установили, что при выполнении резекции почки в условиях тепловой ишемии функциональные показатели почек к 3-м суткам после операции на фоне проводимой в периоперационном периоде эпидуральной блокады соответствовали исходным. В контрольной группе наблюдали нарушения со стороны тубулоинтерстиция и гломерулярного аппарата. Значения СКФ у больных основной группы к 3-м суткам сохранялись в пределах нормальных значений, тогда как у больных контрольной группы СКФ была снижена относительно исходных значений на 38,8% (p<0,05). Заключение. Применение в периоперационном периоде эпидурального блока у больных локализованным раком почки, подвергнутых резекции органа в условиях тепловой ишемии, оказывает нефропротективное влияние, обеспечивая сохранение функциональных показателей почек на исходном уровне. Ключевые слова: локализованный рак почки; тепловая ишемия; острое почечное повреждение; маркеры острого почечного повреждения; эпидуральная блокада The purpose of the study is to investigate the effect of epidural block on the functional state of the kidneys in patients with localized cancer during kidney resection under the conditions of warm ischemia. Materials and methods. We examined 45 patients (25 men and 20 women) with a localized kidney cancer (T 1 N 0 M 0) aged 56.5±8.7 years. All the patients underwent kidney resection performed under conditions of warm ischemia (15-20 minutes). Patients were divided into 2 groups: the main group (25 subjects) in which the perioperative epidural block was applied and the reference group (20 patients) without the epidural block. The following parameters were tested in blood and urine using the ELISA technique: cystatin C, L-FABP, KIM-1 , IL-18, and GFR. The test was carried out 1 hour prior to surgery, 20 minutes after the warm ischemia stage, and on Days 1 and 3. Based on the baseline cystatin С level, the patients in each group were divided into 2 subgroups: subgro...

Objective: to assess perspectives using biomarkers for early detection of developing acute kidney injury (AKI) among patients during partial nephrectomy under the warm ischemia of the kidney. Materials and methods: data of 100 patients was assessed with a localized renal cancer Т1N0М0 aged 56,5±8,7 years. All the patients underwent partial nephrectomy under warm ischemia of the kidney. The concentration of the following “early markers of AKI” was tested in blood of the patients using the ELISA technique and standard test-systems: cystatin С (BioVendor, Czech Republic), NGAL (BCMDiagnostics, USA), L-FABP (Hycult Biotechnology, Netherlands). The duration of warm ischemia was also fixed and the rate of diuresis was valued either. The test was carried out 24 hours prior to and 16 hours after the surgical interference. All the patients were diagnosed and classified by the presence or absence of AKI during the early postoperative period according to the generally accepted classification KDIGO. The obtained results were processed with the help of Microsoft Excel software, the statistical reliability of the results was defined on the basis of the use of Wilcoxon non-parametric test. Simultaneously the expert analysis of the clinical data and results of the laboratory research was carried out. Results: the method of the early diagnostics of AKI among patients who underwent partial nephrectomy under the warm ischemia of the kidney was developed. The method is based on the successive identification of the concentration of the early biochemical markers of AKI, the duration of warm ischemia and the rate of diuresis. Conclusions: the use of the developed method allows diagnosing the development of AKI among patients undergoing partial nephretomy under the warm ischemia already in 16 hours after the surgical interference (before the rise in the creatinine level).

Improved knowledge of molecular mechanisms of the damaging effect of thermal ischemia and reperfusion to renal tissue of patients with renal cancer has significant prospects for new therapeutic approaches aimed at enhancing quality of care. THE AIM: to study changes in the expression of apoptosis-regulating genes MDM 2, BAX, CASP7, CASP3, CASP8, CASP9, BCL2, CASP8 / FADD, p53, APAF1, AIFM1, ICAD and XIAP in renal tissue of patients with renal cell carcinoma subjected to the action of ischemia and reperfusion. PATIENTS AND METHODS. We used for the study tissue biopsies of 12 patients with histologically confirmed diagnosis of renal cancer. Needle biopsy was performed before stop the blood supply, for 10 minutes of ischemia and 20 minutes after reperfusion in the kidney. The relative expression of genetic loci was determined by real-time PCR. RESULTS. It was found: 1) absence from the 10th minute of ischemia significant differences transcriptome profile of the majority of investigated genes from similar parameters prior to ischemia, with the exception of reducing expression of genes CASP7 and ICAD; 2) a significant increase in expression of pro-apoptotic genes (BAX, CASP3/7, APAF1 and p53), and anti-apoptotic genes (XIAP, MDM2 and BCL2) 20 minutes after reperfusion of the kidney tissue; 3) a changes in the balance of expression of pairs of proand anti-apoptotic genes p53 / MDM2 and Bax / BCL2 in the 10th minute of ischemia and 20 minutes after reperfusion. CONCLUSION. These data characterize transcriptomic state of renal tissue in the early period after ischemia and restore the blood flow in it as the initiation point shift the balance of proand anti-apoptotic genes.