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Scientific Reports Jun 2024Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen...
Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen leading to structural damage. The application of intraluminal oxygen has been successfully tested in small-animal series during storage and transport of the organ but have been so far clinically unrelatable. In this study, we tested whether a simple and clinically approachable method of intraluminal oxygen application could prevent ischemic damage in a large animal model, during warm ischemia time. We utilised a local no-flow ischemia model of the small intestine in pigs. A low-flow and high-pressure intraluminal oxygen deliverance system was applied in 6 pigs and 6 pigs served as a control group. Mucosal histopathology, hypoxia and barrier markers were evaluated after two hours of no-flow conditions, in both treatment and sham groups, and in healthy tissue. Macro- and microscopically, the luminal oxygen delivered treatment group showed preserved small bowel's appearance, viability, and mucosal integrity. A gradual deterioration of histopathology and barrier markers and increase in hypoxia-inducible factor 1-α expression towards the sites most distant from the oxygen application was observed. Intraluminal low-flow, high oxygen delivery can preserve the intestinal mucosa during total ischemia of the small intestine. This finding can be incorporated in methods to overcome small bowel ischemia and improve intestinal preservation for transplantation.
Topics: Animals; Intestinal Mucosa; Intestine, Small; Oxygen; Swine; Ischemia; Disease Models, Animal; Organ Preservation; Hypoxia-Inducible Factor 1, alpha Subunit
PubMed: 38877069
DOI: 10.1038/s41598-024-64660-x -
Transplantation Jun 2024This study examined 1071 adult primary kidney transplants from the French-controlled donation after the circulatory determination of death (cDCD) program, which uses...
BACKGROUND
This study examined 1071 adult primary kidney transplants from the French-controlled donation after the circulatory determination of death (cDCD) program, which uses normothermic regional perfusion (NRP), and involves short cold ischemia times (CIT) and constrained asystole times differing by donor age.
METHODS
Logistic regression identified risk factors for primary nonfunction (PNF), delayed graft function (DGF), and graft failure.
RESULTS
Risk factors for PNF included donor hypertension, admission for ischemic vascular stroke, and HLA DR mismatches. Risk factors for DGF included functional warm ischemia time >40 min, dialysis >2 y, recipient body mass index of 30 kg/m2 or higher, recipient diabetes, and CIT >10 h. Risk factors for 1-y graft failure included donor hypertension, donor lung recovery, ostial calcification, recipient cardiovascular comorbidities, and HLA DR mismatches. A high donor estimated glomerular filtration rate protected against DGF and graft failure at 1-y. After adjustment restricted to recipient and graft factors and donor age, the risks of PNF, DGF, and graft failure increased with donor age up to 65 y and then remained stable.
CONCLUSIONS
The study suggests that cDCD kidney transplants are highly successful, but also that its outcomes are influenced by lung recovery, poor HLA DR matching, and warm ischemia times differing with donor age. Our study identified several risk factors for kidney transplantation failure after cDCD with systematic use of NRP and some of them seem as modifiable variables associated with cDCD transplant outcome.
PubMed: 38872246
DOI: 10.1097/TP.0000000000005102 -
American Journal of Physiology. Renal... Jun 2024Kidneys from donors with prolonged warm and cold ischemia are prone to post-transplant T cell-mediated rejection (TCMR) due to ischemia-reperfusion injury (IRI)....
Kidneys from donors with prolonged warm and cold ischemia are prone to post-transplant T cell-mediated rejection (TCMR) due to ischemia-reperfusion injury (IRI). However, the precise mechanisms still remain obscure. Renal tubular epithelial cells (TECs) are the main target during IRI. Meanwhile, we reported previously that murine double minute 2 (MDM2) actively participates in TEC homeostasis during IRI. In this study, we established a murine model of renal IRI and a cell model of hypoxia/reoxygenation by culturing immortalized rat renal proximal tubule cells (NRK-52E) in a hypoxic environment for different time points followed by 24 hours of reoxygenation or incubating NRK-52E cells in a chemical anoxia/recovery environment. We found that during renal IRI, MDM2 expression increased on the membrane of TECs and aggregated mainly on the basolateral side. This process was accompanied by a reduction of a transmembrane protein programmed death-ligand 1 (PD-L1), a co-inhibitory second signal for T cells in TECs. By using mutant plasmids of MDM2 to anchor MDM2 on the cell membrane or nuclei, we found that the upregulation of membrane MDM2 could promote the ubiquitination of PD-L1 and lead to its ubiquitination-proteasome degradation. Lastly, we set up a co-culture system of TECs and CD4+ T cells in vitro; our results revealed that the immunogenicity of TECs was enhanced during IRI. In conclusion, our findings suggest that the increased immunogenicity of TECs during IRI may be related to ubiquitinated degradation of PD-L1 by increased MDM2 on the cell membrane, which consequently results in T cell activation and TCMR.
PubMed: 38867673
DOI: 10.1152/ajprenal.00200.2023 -
European Review For Medical and... May 2024The primary surgical techniques used to treat localized renal tumors are laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN). Obese... (Comparative Study)
Comparative Study
OBJECTIVE
The primary surgical techniques used to treat localized renal tumors are laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN). Obese patients have more intra-abdominal fat accumulation, which may make the localization and operation in minimally invasive surgery more complicated. Currently, limited research has been conducted on which method is more suitable for performing a partial nephrectomy on obese individuals. The aim of our investigation was to analyze and compare the perioperative results associated with both approaches to offer valuable information about the selection of LPN or RAPN as an optimal choice when performing a partial nephrectomy in obese patients.
PATIENTS AND METHODS
We retrospectively collected clinical data from 78 cases of obese individuals [Body mass index (BMI) > 28] who underwent RAPN, as well as 50 cases of obese individuals (BMI > 28) who underwent LPN. The analysis covered various aspects, including initial patient characteristics, glomerular filtration rate (GFR), warm ischemia time (WIT), operation time, volume of blood loss during the surgical procedure, time taken to recover bowel function, positive surgical margin rate, incidence of postoperative complications, and postoperative hospital stay.
RESULTS
We observed that RAPNs exhibited shorter warm ischemia time and reduced intraoperative blood loss in obese patients, along with decreased postoperative duration of abdominal drainage and hospitalization periods compared to LPNs.
CONCLUSIONS
In obese patients, RAPN demonstrates advantages over LPN in minimizing intraoperative blood loss, WIT, and facilitating postoperative recovery. These findings may serve as valuable evidence when considering the choice between LPN or RAPN for partial nephrectomy in obese individuals.
Topics: Humans; Nephrectomy; Laparoscopy; Obesity; Robotic Surgical Procedures; Female; Middle Aged; Male; Retrospective Studies; Kidney Neoplasms; Treatment Outcome; Aged; Postoperative Complications; Adult; Length of Stay; Operative Time
PubMed: 38856133
DOI: 10.26355/eurrev_202405_36294 -
Frontiers in Veterinary Science 2024A dog with bilateral renal dioctophymosis presented with stage 5 acute kidney injury, weight loss, vomiting, apathy, and hematuria. Laboratory tests showed creatinine of...
A dog with bilateral renal dioctophymosis presented with stage 5 acute kidney injury, weight loss, vomiting, apathy, and hematuria. Laboratory tests showed creatinine of 17.2 mg/dL and eggs in the urine. It underwent a 30-min session of hyperbaric oxygen preconditioning at a pressure of 2 ATA. Subsequently, bilateral nephroscopy was performed, without warm ischemia, using Amplatz-type renal dilators. Five parasites were removed, three females from the right kidney, one female from the left kidney, and one male from the abdominal cavity. After surgery, the patient continued doing daily hyperbaric oxygen therapy (HBOT) sessions and clinical therapy. Postoperative care consisted of analgesics, antimicrobials, antioxidants, gastric protector and fluid therapy. Ultrasound monitoring showed a reduction in the area of renal dilation and the hematological and biochemical tests showed rapid recovery from acute kidney injury. There was no bacterial growth in the urine sample collected directly from the kidneys. The patient had an excellent clinical progression and was discharged from hospital 7 days postoperatively, with creatinine values of 2.9 mg/dL. This is the first report of the use of nephroscopy in the treatment of dioctophymosis and indicates excellent chances of cure even in severe cases of bilateral parasitosis. HBOT was shown to be an ally in the clinical therapy of patients with by helping with stabilization and postoperative recovery.
PubMed: 38840630
DOI: 10.3389/fvets.2024.1396467 -
Tissue Engineering. Part A Jun 2024The persistent challenge of organ scarcity in liver transplantation leads to an escalating dependence on organs obtained from extended criteria donors (ECD)....
BACKGROUND
The persistent challenge of organ scarcity in liver transplantation leads to an escalating dependence on organs obtained from extended criteria donors (ECD). Normothermic machine perfusion (NMP) is used for improved preservation. Due to the mimicked in vivo conditions during normothermic machine perfusion, the liver is metabolic active, which allows quality assessment during perfusion. Bile seems to be of rising interest in clinical studies since it is easily collectible for analysis. As there is currently no data on biliary bile acids during NMP, the primary objective of this study was to use our experimental rodent NMP model to assess changes in bile composition through organ damage during perfusion to inform clinical evaluation of donor organs during NMP.
METHODS
30 livers from male Sprague Dawley rats in five groups and underwent 6 hours of NMP using either erythrocyte-supplemented DMEM or Steen solution, with or without 30min of warm ischemia time (WIT). We conducted regular measurements of AST, ALT, LDH, and urea levels in the perfusate at three-hour intervals. Bile samples were analyzed for biliary pH, LDH and GGT as well as biliary bile acids via mass spectrometry and UHPLC.
RESULTS
Compared to regular livers, liver injury parameters were significantly higher in our donation after circulatory death (DCD) model. Bile production was significantly reduced in livers exposed to WIT, and the bile showed a significantly more alkaline pH. This correlated with the concentration of total bile acids, which was significantly higher in livers experiencing WIT. However, regular livers produced a higher total amount of biliary bile acids during perfusion. Taurocholic acid and its metabolites were most prominent. Secondary bile acids were significantly reduced during perfusion due to the missing enterohepatic circulation.
CONCLUSIONS
WIT-induced liver injury affects bile composition within our small animal NMP model. We hypothesize this phenomenon to be attributed to the energy-driven nature of bile secretion, potentially explaining why DCD livers produce less, yet more concentrated, bile. Our results may inform clinical studies, in which biliary bile acids might have a potential as a quantifiable viability marker in human NMP liver transplantation studies.
PubMed: 38832856
DOI: 10.1089/ten.TEA.2024.0048 -
Surgical Innovation Jun 2024Prolonged warm ischemia time (WIT) in kidney transplantation is associated with numerous adverse outcomes including delayed graft function and decreased patient and...
Prolonged warm ischemia time (WIT) in kidney transplantation is associated with numerous adverse outcomes including delayed graft function and decreased patient and graft survival. Circumventing WIT lies in maintaining renal hypothermia and efficiently performing the vascular anastomosis during this portion of the procedure. Although numerous methods of intra-operative renal cooling have been proposed, most suffer from practical limitations, and none have been widely adopted. Herein we describe a novel device specifically designed to maintain renal hypothermia during kidney transplant surgery. Aluminum tubing was organized in a serpentine pattern to create a malleable, form-fitting cooling jacket to manipulate renal allografts during transplant surgery. Adult porcine kidneys were used to test the device with 4°C saline as coolant. Kidneys were placed at 24°C; surface and core temperatures were monitored using implanted thermocouples. Anastomosis of porcine kidney vessels to GORE-TEX® vascular grafts in an ex-vivo operative field was performed to assess the functionality of the device. The device maintained surface and core graft temperatures of ≤5°C after 60 minutes of WIT. Furthermore, the device provided hands-free retraction and support for the allograft. We found that ex-vivo anastomosis testing was enhanced by the presence of the cooling jacket. This proof-of-concept study demonstrated that our novel device is a practical tool for renal transplantation and can maintain sufficiently cool graft temperatures to mitigate WIT in an ex-vivo setting. This device is the first of its kind and has the potential to improve kidney transplant outcomes by eliminating WIT during graft implantation.
PubMed: 38831684
DOI: 10.1177/15533506241260087 -
Cureus May 2024Introduction As the field of laparoscopic living donor nephrectomy (LLDN) has progressed over the years, there has been a growing emphasis on optimizing surgical...
Introduction As the field of laparoscopic living donor nephrectomy (LLDN) has progressed over the years, there has been a growing emphasis on optimizing surgical techniques and outcomes to ensure the safety and well-being of living kidney donors. The early experiences with right LLDN, marked by challenges and concerns such as high conversion rates to open surgery and early graft loss due to technical reasons, prompted a reevaluation of the approach toward right-sided donor nephrectomies. In this article, we aim to compare the safety and efficacy of right LLDN to left LLDN performed in our centers and to provide valuable insights that can ultimately enhance patient outcomes and ensure the well-being of living organ donors. Methods Between January 2018 and January 2022, we conducted 16 cases of right LLDN and compared them with 134 cases of left LLDN procedures done in the Kingdom of Bahrain and Jordan over the same time period. We analyzed differences in donor age, sex, operative time, warm ischemia time (WIT), graft function, complications, and conversion to open technique. Patient data and surgical outcomes were extracted from medical records and surgical databases. Statistical analysis was conducted to identify significant differences between the two groups. Categorical variables such as complications and safety outcomes were compared using chi-square tests and logistic regression analysis. The primary outcomes of interest included safety metrics such as complication rates, vascular complications, graft loss, and postoperative serum creatinine levels for the recipients. Results Our study showed similar demographics in both groups. However, the operative time was shorter for the left LLDN, with 81 minutes compared to 96 minutes for the right. Warm ischemia times (WITs) were comparable at 4.5 minutes for the left and 5.2 minutes for the right. There was less incidence of delayed graft function on the left side (none in the left group compared to one case in the right group). Both groups had similar six-month graft function in terms of serum creatinine levels (0.98 mg/dL for the left and 1.2 mg/dL for the right), hospital stays (2.5 days for the left and 2.8 days for the right), and estimated blood loss (EBL) (90 mL for the left and 50 mL for the right). Additionally, no blood transfusions were required in either group, but there was one case of conversion to open surgery in the right LLDN group. Conclusion Our data confirm the safety and efficacy of the right LLDN, consistent with the current literature. This increases the cumulative evidence supporting the use of laparoscopic retrieval on the right side when indicated.
PubMed: 38826980
DOI: 10.7759/cureus.59562 -
Annals of Surgical Oncology Jun 2024This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted...
BACKGROUND
This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors.
METHODS
A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups.
RESULTS
We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020).
CONCLUSIONS
The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.
PubMed: 38824192
DOI: 10.1245/s10434-024-15470-y -
The French Journal of Urology May 2024Ligation of the renal pedicle is a crucial step in laparoscopic renal harvesting. Currently, two devices are widely used: Hem-o-Lok® clips and staplers. Each has its...
INTRODUCTION
Ligation of the renal pedicle is a crucial step in laparoscopic renal harvesting. Currently, two devices are widely used: Hem-o-Lok® clips and staplers. Each has its advantages and disadvantages.
METHODS
A systematic literature review was conducted following the PRISMA methodology on PubMed, EMBASE, and Cochrane databases with no time restrictions. Registered in the PROSPERO database (CRD42023460585), the study's primary outcome measures include the failure rate of the ligation tool, conversion to open surgery, rate of severe bleeding, and device-related death. Other secondary variables are also explored. An assessment of the quality of included comparative studies was performed using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool.
RESULTS
Out of 393 articles identified using our keywords, 32 were included. Overall, clips have a lower failure rate during application, elongate graft vessel length, and are more cost-effective. Staples are associated with a shorter warm ischemia time and lower blood loss. There is no significant difference between the two devices in terms of conversion, severe bleeding, death, and blood transfusion.
CONCLUSION
There is no perfect modality for renal pedicle control during laparoscopic harvesting, as each instrument has its pros and cons. Hem-o-Lok® clips are a safe and cost-effective option, particularly suitable for right-sided harvesting or in cases of vascular variations. However, they are still associated with a risk of secondary displacement with potentially serious consequences. Certain technical tricks can mitigate this risk.
PubMed: 38821383
DOI: 10.1016/j.fjurol.2024.102656