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Objective: to analyze the immediate and long-term outcomes of kidney transplantation (KT) depending on the duration of delayed graft function (DGF). Materials and methods. The study conducted a retrospective analysis of KT outcomes in 312 patients operated on at Botkin Hospital from June 2018 to December 2022. Exclusion criteria were primary non-function, severe surgical complications that required emergency transplantectomy in the first week after KT and cases where a comprehensive approach to DGF prevention was applied. DGF was defined as the need for dialysis within the first 7 days of KT. The severity of this complication was assessed by the time it took the transplanted kidney function to normalize from mild DGF to severe. We analyzed the immediate and long-term outcomes of KT depending on the presence of initial function and the severity of DGF. Results. DGF developed in 25.3% of cases. The mean time for graft function normalization was 16.5 ± 6.8 days. Mild DGF occurred in 68% of cases, severe DGF was determined in the remaining cases (32%). The incidence of complications was statistically significantly higher in the severe DGF group: 14/25 (56%) vs. 15/54 (27.8%) (p = 0.047). There were also no significant differences in the rate of complications between recipients with immediate and mild DGF: 43/233 (18.4%) vs. 15/54 (27.8%) (p > 0.05). Severe DGF lasting for more than 2 weeks had a statistically significant association with postoperative complications (p = 0.047) and with decreased long-term graft survival (log-rank p = 0.021). Conclusion. Development of severe DGF mainly depends on donor characteristics, timing and peculiarities of graft preservation. Nevertheless, other factors, such as acute calcineurin inhibitor nephrotoxicity, should not be ignored. Therefore, prevention of all potentially modifiable risk factors for DGF should go hand in hand with the expansion of the indications for donation.

Objective: to determine the efficacy and safety of an integrated strategy aimed at preventing delayed renal graft function (DGF).Materials and methods. From June 2018 to December 2022, 478 deceased-donor kidney transplants were performed at Botkin Hospital, Moscow. The patients were divided into two groups: Group I consisted of 128 patients who did not use the integrated strategy; Group II included 67 patients in whom the DGF prevention strategy was used at the perioperative stage. The integrated strategy involved the use of hypothermic oxygenated machine perfusion (HOPE) using expanded criteria donors, the use of a second warm ischemia (SWI) elimination device, personalized initial calcineurin inhibitor (CI) dosing, and use of alprostadil for high vascular resistance in renal graft arteries.Results. DGF occurred in 5 of 44 patients (11.4%) that used the integrated strategy, and in 13 of 44 patients (29.5%) in the control group. The differences were statistically significant (p = 0.034), there was a medium strength relationship between the traits (V = 0.225). The use of the integrated DGF prevention approach reduced the chances of developing DGF by a factor of 0.3 (95% CI: 0.1–0.95). The risk of DGF in the integrated strategy group was 61.3% of the risk of DGF in the non-strategy group, thus the relative risk (RR) is 1.63 (95% CI: 1.1–2.4). Median duration of graft function normalization was statistically significantly lower in group II: 5 (IQR: 3–9) versus 15 (IQR: 7–19) days (p = 0.012). Mean length of hospital stay was 19.1 ± 4.2 (95% CI: 14.5–26.1) bed-days in group I and 13.9 ± 3.4 (95% CI: 9.3–17.2) bed-days in group II. Differences in this indicator were also statistically significant (p = 0.043).Conclusion. The set of DGF prevention measures, developed at Botkin Hospital, evidence-based and implemented in clinical practice, can reduce the burden of modifiable risk factors of this complication significantly, thereby improving treatment outcomes for kidney transplant recipients considerably.

Objective: to evaluate the effectiveness of a new device for second warm ischemia (SWI) elimination in kidney transplantation (KT).Materials and methods. The study included clinical and experimental stages. The clinical stage included 63 patients out of 219 who underwent KT at Botkin Moscow City Clinical Hospital between July 2018 and August 2022. The inclusion criteria were kidneys from donation after brain death (DBD) donors with expanded criteria or kidneys from donation after circulatory death (DCD) donors, and an SWI time greater than 45 minutes. The first group consisted of 24 recipients operated on using the new SWI elimination device. The second retrospective control group consisted of 39 patients where sterile ice bags were used at the implantation stage. The groups had no statistically significant differences in the main recipient and donor characteristics, as well as in perioperative parameters. Also, from November 2021 to April 2022, 23 kidney autotransplantation experiments in female Landrace pigs were performed. The animals were cared for in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 18 March 1986). Efficiency of different SWI elimination techniques was compared on two experimental models: standard donor (group 1, n = 12) and asystolic donor (group 2, n = 11).Results. In the clinical trial group, mean graft temperature (tm) before reperfusion was statistically significantly lower in group 1 using the special SWI elimination device: 6.4 ± 1.7 °C (95% CI 3.2–8.5) versus 22.1 ± 2.3 °C (18.1–24.6), р < 0.001. The risk of delayed graft function (DGF) was 3.86 times higher (95% CI 1.11–13.43) with the standard SWI elimination technique. In the experimental group, in the subgroups using the new device (n = 12), graft tm before reperfusion was 5.1 ± 0.4 °C (95% CI 4.5–5.8), whereas in the ice bag subgroups (n = 11), tm was 29.3 ± 1.3 °C (95% CI 27.7–30.8), which was significantly higher (p < 0.001). The overall 1-week survival of the experimental animals was significantly higher in the SWI elimination device subgroup (logrank p = 0.036).Conclusion. The developed device is effective in eliminating SWI of renal graft.

Objective: to develop a personalized algorithm for extended-release tacrolimus in kidney recipients and to analyze its early outcomes in comparison with a retrospective control group.Materials and methods. The first (I) control group «Standard Protocol» included 228 patients operated on at Botkin City Clinical Hospital from June 2018 to November 2021; tacrolimus was administered postoperatively in a starting standard dosage of 0.2 mg/kg. The second group (II) consisted of 75 patients operated from December 2021 to November 2022, whose postoperative treatment involved a personalized extended-release tacrolimus dosing protocol. Induction immunosuppression was similar in both groups. The target tacrolimus level in the early postoperative period was considered to be 10-12 ng/ml for all patients. The comparison criteria included incidence of Over-immunosuppression (tacrolimus C0 >15 ng/ml), incidence of acute rejection and infectious complications in the first month after surgery, incidence and duration of delayed graft function (DGF), and length of stay at the hospital.Results. Over-immunosuppression was statistically significantly lower in the personalized protocol group, with 36.7% in group I and 87.5% in group II (p < 0.001). There was also a lower incidence of early infectious complications in group II: 5.4% vs. 13.2%, however, without reaching a level of statistical significance (p = 0.088). DGF incidence in group I and group II were 25.4% (58/228) and 22.7% (17/75), respectively. The length of stay at the hospital in group II was also statistically significantly lower: 13 versus 19 bed days (p = 0.033). In both subgroups, no patient developed acute rejection in the first month after surgery (p = 1).Conclusion. The personalized dosing protocol that was developed for extended-release tacrolimus in kidney recipients achieves the target levels of the drug recommended for the early postoperative period with low risk of under-immunosuppression and associated acute graft rejection, with a significantly lower incidence of over-immunosuppression.

Objective: to present an analysis of the results of 100 cadaveric liver transplants performed at Botkin Hospital from July 2018 to October 2021. Materials and methods. From July 2018 to October 2021, 100 orthotopic liver transplantation (LTx) from a deceased donor were performed at the surgical clinic of Botkin Hospital. The recipients were 58 males (58%) and 42 females (42%). The mean age of the recipients was 48.73 ± 8.56 (24–66) years, while their mean MELD was 19.54 ± 4.35 (15–33). The main indications for LTx were cirrhosis resulting from chronic viral hepatitis (CVH) C (52%), nutritional-toxic cirrhosis (20%), autoimmune liver and bile duct disease (18%), CVH B (7%), and hepatocellular carcinoma (HCC) (3%). During the period under study, 119 potential liver transplant donors were evaluated. The mean age of the donors was 44.2 ± 11.12 (21–63) years. Median levels of sodium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin were 141 (138–146) mmol/L, 27 (20.7–47.4) units/L, 25 (17–41.5) units/L, and 9.65 (6.42–13.7) μmol/L, respectively. The median graft hepatic steatosis was 10% (5–15). LTx was performed using the piggyback technique (99/100 cases) and classic technique with inferior vena cava resection (1/100). End-to-end porto-portal vein anastomosis was performed (99/100 cases). Anastomosis of the donor organ’s portal vein with the recipient’s left gastric vein due to occlusive thrombosis of the recipient’s portal vein was carried out (1/100). In all cases, a continuous end-to-end arterial anastomosis was formed. End-to-end choledochocholedochal anastomotic strictures (95/100) and end-to-side hepaticojejunostomy (5/100) were formed. Results. Median cold ischemia time was 312.5 minutes (280–380). Mean operative time was 488.91 ± 65.34 (95% CI: 475.9–501.9) minutes, median intraoperative blood loss was 1000 (600–1500) mL. Thirty-day mortality was 2% (Clavien–Dindo class V). Early postoperative complications (Clavien–Dindo class IIIa–IVa) developed in 12/100 patients (12%). Graft arterial thrombosis occurred in 3 cases (3%), biliary anastomotic strictures in 6 (6%), and subhepatic hematoma in 2 (2%). The average intensive care unit (ICU) bed day was 2.34 ± 1.67 (1–8). Total postoperative bed-day was 14.63 ± 5.35 (10–39). During case follow-up, a prolonged form of calcineurin inhibitor (CNI) was administered as immunosuppressive therapy in mono regimen (85 patients), in combination with mycophenolic acid derivatives (7), and in combination with everolimus (6). Of the 93 patients, 46 patients (49.46%) had the new coronavirus infection (COVID-19) before or after transplantation; in no case did COVID-19 lead to death. Six patients (13.04%) were hospitalized due to COVID-19. To date, 33/93 (25.48%) patients have been vaccinated, resulting in 75 (75%) liver transplant recipients immune to COVID-19. The overall 1-year survival rate was 95% and the 3-year survival rate was 91%. Conclusion. Introduction of LTx in multidisciplinary hospitals allows to, already at the start of the program, achieve immediate and long-term treatment outcomes (in decompensated diffuse liver disease) that are comparable to those of leading transplantation centers.

Objective: to demonstrate, using a clinical case, the first successful experience in a combined use of an automated chest compression device (ACCD) and hypothermic oxygenated machine perfusion (HOPE) for kidney transplantation from a donor with irreversible cardiopulmonary arrest. Materials and methods. In the presented clinical case, ACCD was successfully used in a donor who was pronounced dead following an irreversible cardiopulmonary arrest. This allowed to minimize the primary warm ischemia time. Kidney graft HOPE for 585 minutes reduced the static cold storage time to 165 minutes. Results. In the uneventful postoperative period, there was immediate kidney graft function. This allowed for rapid rehabilitation and discharge from hospital. Conclusion. Introduction of ACCD and HOPE will increase the number of donor organs, mainly kidneys intended for transplantation.

Objective: to evaluate the safety and efficacy of hypothermic oxygenated machine perfusion (HOPE) for kidney grafts obtained from expanded criteria donors (ECD).Materials and methods. From June 2018 to June 2021, 200 surgeries involving kidney transplants from deceased donors were performed at Botkin City Clinical Hospital. Of these, 123 were men (61.5%) and 77 were women (38.5%). The mean age was 47.62 ± 11.69 (20–73) years. In 102 cases, kidney grafts were procured from ECD. In 92 recipients (90.2%) of kidney transplants from an expanded criteria donor, static cold storage done according to the standard technique was used to preserve the organ; these patients constituted observation group 1. In 10 recipients (9.8%), hypothermic oxygenated perfusion was used in addition to static cold preservation; these patients formed observation group 2.Results. No 30-day mortality was recorded in both observation groups. The mean static cold storage time in group 1 patients was 612.33 ± 178.88 (133–1180) minutes. Overall incidence of delayed graft function was 26.5% (53/200). Incidence of delayed graft function was 19.3% (19/98) for organs from standard donors using static cold storage and 35.8% (33/92) for ECD organs. Twenty-five patients (12.5%) had postoperative complications. Postoperative complications with delayed graft function were diagnosed in 12 patients, which was 22.6% (12/53), with immediate function in 13 patients, which was 8.8% (13/147). Mean cold storage time in group 2 patients was 319.11 ± 110.24 (311–525) minutes. Mean HOPE time was 202.34 ± 21.48 (150–210) minutes. Delayed graft function was recorded in 1 group 2 patient (10%). No complications, including perfusion-related one, were recorded in this group.Conclusion. The unique technique used at Botkin City Clinical Hospital for HOPE in kidney transplant is safe. It provides a low risk of delayed graft function for ECD kidneys.

Objective: to evaluate the effectiveness of vacuum-assisted closure (VAC) therapy in comparison with standard treatments for infected and chronic non-healing wounds after kidney transplantation. Materials and methods. From June 2018 to November 2019, 75 kidney transplants from deceased donors were performed at the Transplantation Ward of Botkin City Clinical Hospital. There were 47 men (62.6%) and 28 women (37.4%). Standard surgical technique was used. Immunosuppressive therapy was carried out according to a three-component scheme with anti-CD25 monoclonal antibody induction (basiliximab) intraoperatively and on day 4. All patients received antibiotic therapy with protected third-generation cephalosporins for 7 days after surgery. Postoperative complications were evaluated according to the Clavien-Dindo classification. Standard methods, including daily dressings using modern dressing materials (group I) and VAC therapy (group II) were used for treating infected and chronic non-healing wounds. Results. 30-day mortality in the postoperative period was zero. Postoperative complications were recorded in 11 patients (14.6%), of which 7 had postoperative wound complications. Group I included 3 patients (1 with a Klebsiella pneumonia-infected wound and 2 with chronic non-healing wounds and no microflora growth). Group 2 had 4 patients (3 with infected wounds (Esherichia coli - 1, Klebsiella pneumonia - 2) and 1 with chronic non-healing wound). Complete cleansing of wound, absence of bacterial growth according to the microbiological examination, and maturation of granulations according to histological examination were considered as the criteria upon which a wound could be sutured in both groups of patients. The average time between the start of treatment and secondary suturing in group 1 patients was 33.11 ± 5.43 (28-37) and 15.01 ± 3.15 (13-17) days in group 1 and group 2 respectively. Conclusion. VAC therapy in patients with wound complications resulting from kidney transplantation, in comparison with standard treatment, can achieve rapid wound cleansing, acute inflammation relief and accelerated maturation of mature granulation tissue, thereby improving treatment outcomes in this category of patients.

Objective: to evaluate the first results of the Botkin Hospital transplant program. Materials and methods. From June 2018 to October 2019, 100 solid organ transplants were performed at the Botkin City Clinical Hospital. Out of the 100 transplantations, 72 were kidney transplants (average age of recipients was 45.65 ± 11.35 years, HLA match averaged 2.09 ± 1.03) and 28 were liver transplants (average age of recipients was 50.14 ± 7.62 years, average MELD was 17.78 ± 3.28 (14–34). Results. After transplantation, there was no 30-day mortality. Postoperative complications following kidney transplantation were established in 11 patients (15.2%). In 3 patients (4.3%) – suppuration of postoperative wound, in 2 patients (2.8%) – hematomas in the area of the postoperative suture during hemodialysis, in 5 patients (6.9%) – retroperitoneal lymphocele, in 1 patient (1.4%) – urosepsis. There were 4 cases (5.5%) of acute rejection, 3 cases (4.2%) of humoral rejection, and 1 case (1.3%) of cellular rejection. Early postoperative complications following liver transplantation were detected in 2 patients (7.2%). In one patient – hematoma under the right lobe of the liver on the 1st day after surgery, the diaphragm was the source of bleeding, in one patient – ascites leakage through postoperative sutures, which required relaparotomy. In 2 patients (7.2%), postoperative complications were found in the separated postoperative period. In one case, of choledochocholedochal anastomotic stricture – stricture stenting was performed with coated nitinol stent. In another case, acute adhesive intestinal obstruction, which required laparotomy, adhesiolysis. Conclusion. Implementation of the transplantation program in multidisciplinary hospitals can boost transplant care in a district and improve the treatment results of patients with terminal organ damage.

Ischemic and reperfusion injury is a complex, multifactorial process that damage kidney transplant. Knowledge and understanding of pathogenic mechanisms of damage processes allows the use of various biological agents to reduce this damage. However, the application of most of biological agents is still only in the experiment. The purpose of this survey show participants of pathogenetic mechanisms, mainly inflammatory mediators (cytokines, chemokines), their interactions, and the consequences of their damaging effects on the fabric kidney transplant.

The morphofunctional status of peripheral blood platelets from 16 recipients, 16 optimal and 16 marginal donors renal allograft were investigated by method of vital computer phase morphometry (phase-interference microscope «Cytoscan»). The abnormality of platelet hemostasis was found out in recipients and potential renal allograft donors. Such hemostasis damages can promote the thrombotic complications and failure of microcirculation in renal parenchymatous tissue.