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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 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 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 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.
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