Comprehensive Overview of Innovative Strategies in Preventing Renal Ischemia-reperfusion Injury: Insights from Bibliometric and In Silico Analyses.

BACKGROUND: Ischemia-Reperfusion Injury (IRI) is a complex pathophysiological process with severe consequences, including irreversible loss of renal function. Various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and kidney reperfusion. AIM: This comprehensive analysis provides an overview of pharmacological agents and intraoperative methods for preventing and treating renal IRI. METHODS: Our analysis revealed that eplerenone exhibited the highest binding affinity to crucial targets, including Aldehyde Dehydrogenase (AD), Estrogen Receptor (ER), Klotho protein, Mineralocorticoid Receptor (MR), and Toll-Like Receptor 4 (TLR4). This finding indicates eplerenone's potential as a potent preventive agent against IRI, surpassing other available therapeutics like Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. In preventing kidney IRI, our comprehensive analysis emphasizes the significance of eplerenone due to its strong binding affinity to key targets involved in the pathogenesis of IRI. RESULTS: This finding positions eplerenone as a promising candidate for further clinical investigation and consideration for future clinical practice. CONCLUSION: The insights provided in this analysis will assist clinicians and researchers in selecting effective preventive approaches for renal IRI in surgical settings, potentially improving patient outcomes.

Retrograde reperfusion of renal grafts to reduce ischemic-reperfusion injury.

Background: During transplantation, a kidney graft undergoes a cascade of pathological changes, referred to as ischemia-reperfusion injury (IRI), as it is incorporated into the bloodstream. Various studies have reported that retrograde reperfusion (RRP) leads to improved myocardial recovery and could reduce IRI in liver transplantation. This study investigated the effect of RRP in renal transplantation with a focus on reduction of kidney IRI. Methods: Between December 2019 and July 2022, 15 consecutive kidney transplants were performed with retrograde venous reperfusion. To conduct a comparative study and to recruit a control group, 15 kidney transplants that had been performed in the same center by the same two surgeons were retrospectively analyzed. Differences between the two groups were considered statistically significant at P<0.05. Results: The baseline characteristics of the two groups were statistically comparable (P>0.05). The surgical technique for kidney transplantation was the same in both groups. On the first postoperative day, polyuria was less pronounced in the RRP group (P<0.01). Serum creatinine and urea levels and estimated glomerular filtration rates on postoperative days 1, 4, 7, and 30 were lower in the RRP group (P<0.05). Conclusions: Retrograde venous reperfusion of a kidney transplant, preceding antegrade arterial reperfusion, reduced the effects of renal parenchyma IRI. To validate the results of this study, it is necessary to conduct further studies on a larger cohort of patients with a longer follow-up period.

Prognosis of Patients Following Liver Transplant From Deceased and Living Donors.

OBJECTIVES: Liver transplant is the only treatment option for patients with end-stage liver disease. MATERIALS AND METHODS: Liver transplant procedures performed from June 2013 to March 2017 were evaluated. We evaluated the postoperative period in recipients of livers from deceased and living donors. RESULTS: Of 31 liver transplant procedures in 30 recipients, 12 were from deceased and 19 from living donors. The final analysis included 24 liver transplants (11 males, 13 females), with 10 from deceased and 14 from living donors. No deaths or life-threatening and debilitating complications were shown in liver donors. All living-donor liver transplants were performed utilizing the right lobe, the volume of which was calculated using contrast-enhanced computed tomography. Most living-donor liver recipients had viral hepatitis, whereas most deceased-donor liver recipients had autoimmune liver disease. Median age of recipients of deceased donations was 39.3 years (median admission duration of 28.1 days), and median age of recipients of donations from living donors was 45.4 years (median admission duration of 36.4 days). All patients were started on an immunosuppression protocol, which included basiliximab on days 0 and 4, tacrolimus, mycophenolate, and prednisolone. Of 24 recipients, 5 were taking prednisolone 10 mg/day or less at discharge. CONCLUSIONS: Most of our liver transplant procedures were living-donor liver transplants (61.3%). Most patients who received living donations had viral hepatitis, with all cases related to autoimmune liver disease receiving deceased donations. This may be related to the possibility of antiviral therapy controlling all stages of liver disease versus no chance of controlling autoimmune liver disease. Living-donor liver transplant recipients required more time to recover to reach initial liver volume; 20.8% of recipients were discharged with prednisolone of 10 mg/day or less. Our results suggest a need for further development of nonsteroidal immunosuppression strategies to minimize infections and steroid-related adverse effects.

Influence of a modified preservation solution in kidney transplantation: A comparative experimental study in a porcine model.

BACKGROUND/OBJECTIVE: Currently, due to lack of optimal donors, more marginal organs are transplanted. Therefore, there is a high interest to ameliorate preischemic organ preservation, especially for critical donor organs. In this regard, a new histidine-tryptophane ketoglutarate (HTK-N) solution has been designed and its protective efficacy was compared with the standard preservation solutions-University of Wisconsin solution and standard HTK or Custodiol (Bretschneider's solution). METHODS: Seventy-two landrace pigs were included into the study, as donors and recipients. The donor kidneys were perfused during explantation with cold University of Wisconsin solution (n = 12), standard HTK (n = 12), or HTK-N solutions (n = 12), kept in the respective preservation solution at 4°C for 30 hours, implanted in the recipient pigs, and reperfused. The pigs survived in daily control for 7 days. The serum creatinine and blood urea nitrogen were assessed in pre- and postreperfusion phase on the 3rd day and 7th day posttransplantation. Additionally, tissue samples were taken to analyze the histopathological degree of tubular injury and regeneration before and after reperfusion. RESULTS: The three preservation groups were comparable in age, body weight, and hemodynamic parameters. According to statistical proof, they differed in none of the control parameters. CONCLUSION: Although the new preservation HTK solution is in several points a well-thought-out modification of the standard HTK solution, its preservation efficacy, at least for kidney preservation in a pig model for 30 hours, seems to be comparable to the current used solutions. A real advantage, however, could be confirmed in clinical settings, where marginal organs may influence the clinical outcome.

Evaluation of the modified HTK solution in pancreas transplantation-An experimental model.

INTRODUCTION: One of the great challenges in pancreas transplantation is the ischemia reperfusion injury. It is mentioned that free oxygen and/or nitrogen radicals play a prominent role in this phase. To minimize this problem, a modified histidine-tryptophan-ketoglutarate (HTK) solution that contains modified antioxidants has been developed. Our aim was to evaluate this solution in improving the viability of the pancreas in comparison with standard HTK and University of Wisconsin (UW) solutions in a porcine model of pancreas transplantation. MATERIALS AND METHODS: Twenty-three Landrace pigs were divided into three identical groups. After a 10-hour preservation time at 4°C, the pancreas was implanted in the organs of the recipients in a standardized manner. Serum parameters were assessed prior to and after implantation on the 1(st) postoperative day, 3(rd) postoperative day, and 7(th) postoperative day. Furthermore, three biopsies were taken: prior to and after reperfusion, and on Day 7 to assess the grafts. RESULTS: An analysis of serum glucose among the three groups showed no significant differences. Evaluation of the insulin levels showed no significant difference between the modified and standard HTK groups; however, differences between HTK and UW were significant (p = 0.004 in favor of UW solutions). The histopathological results showed a trend of a higher grade of rejection of pancreas tissue in the UW group compared to both HTK groups. CONCLUSION: The modified HTK solution could preserve the pancreas for the preservation of the graft with similar results to those observed for standard solutions without any significant difference. The trend showed that the pathological finding in the UW group was not as good as that in the modified HTK and standard HTK groups.

Liver Transplant Outcomes in a Newly Started Program.

OBJECTIVES: Kazakhstan is experiencing a high demand for liver transplants. More than 1000 patients have end-stage liver disease in the country, and liver transplant is the only viable option for their treatment. MATERIALS AND METHODS: Liver transplant patients, treated from February 2013 to December 2014, were included in this retrospective analysis. RESULTS: From February 2013 to December 2014, seven patients received a liver transplant in our center (1 pediatric patient was excluded). Deceased liver recipients' (n = 3) median age was 52 years and median Model for End-Stage Liver Disease score 9. The indication for transplant was uncontrolled portal hypertension due to autoimmune liver disease. Cadaveric donors' median age was 45 years. Recipients' intensive care unit stay was > 5 days, time on inotropic support was > 3 days. Mean cold ischemic time was > 6 hours, and secondary ischemic time was 67 minutes. One patient in the deceased donor transplant group died during postoperative week 1 from hepatic artery thrombosis. Living donor liver recipients' (n = 3) median age was 47 years (43-48 y) and median Model for End-Stage Liver Disease score was 17 (range 14-20). Liver disease was hepatitis virus related (hepatitis C virus in 1 patient and hepatitis B and D virus in 2 patients). Mean cold ischemic time was 0.43 hours, and mean secondary ischemic time was 64 minutes. One recipient in the living donor liver group died early in the postoperative period from hemorrhage. CONCLUSIONS: Our experience was insufficient to adequately assess morbidity and survival rates in patients for whom the longest follow-up was 25 months. However, no episodes of rejection were observed. Survival rates between living and deceased donor recipients were equivalent, although cadaveric-donor liver conditions were imperfect. This analysis demonstrates the necessity for timely diagnosis of surgical complications, which accounted for all mortality incidence in our series.