Orthotopic Kidney Transplantation Research Articles

Mouse kidney transplantation model: Three novel methods.

The mouse kidney transplantation model presents challenges in terms of surgical difficulty and low success rate, making it difficult to master. This study aims to provide a crucial model for transplantation immunology research by modifying and developing novel techniques for mouse kidney transplantation. A total of 57 pairs of mice were used to establish and compare the modified and innovative surgical techniques for mouse kidney transplantation. Three different surgical models were established, including the abdominal suture technique for orthotopic kidney transplantation, the abdominal cuff technique for orthotopic kidney transplantation, and the cervical cuff technique for ectopic kidney transplantation. BALB/c or C57BL/6 male mice, aged 8 to 12 weeks and weighed 20 to 25 g with specified pathogen free-grade were served as the donor mice or the recipient mice. The surgical technique characteristics, key surgical times, complications, and pathological examination in the early postoperative period were summarized and compared. Three different surgical models of mouse kidney transplantation were successfully established. The comparison of warm ischemic time for the 3 groups of mice showed no statistical significance (P=0.510 4). The abdominal suture group had the shortest total operation time of the donor compared with the abdominal cuff group and the cervical cuff group [(18.3±3.6) min vs (26.2±4.7) min and (22.8±2.5) min; both P<0.000 1]. There was a significant difference in cold ischemia time among the 3 groups (all P<0.000 1), with (60.8±4.1) min in the cervical cuff group, (43.3±5.0) min in the abdominal suture group, and (88.8±6.7) min in the abdominal cuff group. Due to different anastomosis methods, the cervical cuff group had the shortest time [(17.6±2.7) min], whereas the abdominal cuff group had the longest time [(38.8±5.4) min]. The total operation time for the recipients showed significant differences (P<0.000 1), with the abdominal suture group having the shortest time [(44.0±6.9) min], followed by the cervical cuff group [(64.1±5.2) min], and the abdominal cuff group [(80.0±6.0) min] being the longest. In the 32 mice of the abdominal suture group, there were 6 with intraoperative bleeding, including 1 arterial intimal injury bleeding and 5 with bleeding after vessel opening. Six mice had ureteral complications, including ureteral bladder anastomotic stenosis, necrosis, and renal pelvis dilation. Two mice had postoperative abdominal infections. In the abdominal cuff group, there was no intraoperative bleeding, but 6 mice showed mild arterial stenosis and 5 showed venous stenosis, 4 arterial injury, 4 arterial thrombosis, and 2 ureteral complications. No postoperative infections occurred in the mice. In the cervical cuff group, no intraoperative bleeding, arterial intimal injury, arterial/venous stenosis, or thrombosis were found in 13 mice. Five mice had ureteral complications, including ureteral necrosis and infection, which were the main complications in the cervical cuff group. The renal function in mice of the 3 groups remained stable 7 days after surgery. Hematoxylin and eosin staining and periodic acid-Schiff staining showed no significant differences in terms of acute rejection among the 3 surgical methods (all P>0.05). All 3 surgical methods are able to successfully establish mouse kidney transplantation models, with no significant differences observed in the short-term graft survival and acute rejection. The modified abdominal suture technique and abdominal cuff technique have their respective advantages in research applications. The novel cervical cuff technique for ectopic kidney transplantation model is relatively simple to be prepared and causes less trauma to the mice, providing more options for studies involving xenotransplantation, secondary transplantation, and local lymphatic drainage. However, the difficulty in harvesting the donor kidney and the high incidence of ureteral infections need further validation in long-term survival. This study holds important reference value for choosing the type of mouse kidney transplantation model for different research needs.

Evaluating the Effects of Kidney Preservation at 10 °C with Hemopure and Sodium Thiosulfate in a Rat Model of Syngeneic Orthotopic Kidney Transplantation.

Kidney transplantation is preferred for end-stage renal disease. The current gold standard for kidney preservation is static cold storage (SCS) at 4 °C. However, SCS contributes to renal graft damage through ischemia-reperfusion injury (IRI). We previously reported renal graft protection after SCS with a hydrogen sulfide donor, sodium thiosulfate (STS), at 4 °C. Therefore, this study aims to investigate whether SCS at 10 °C with STS and Hemopure (blood substitute), will provide similar protection. Using in vitro model of IRI, we subjected rat renal proximal tubular epithelial cells to hypoxia-reoxygenation for 24 h at 10 °C with or without STS and measured cell viability. In vivo, we preserved 36 donor kidneys of Lewis rats for 24 h in a preservation solution at 10 °C supplemented with STS, Hemopure, or both followed by transplantation. Tissue damage and recipient graft function parameters, including serum creatinine, blood urea nitrogen, urine osmolality, and glomerular filtration rate (GFR), were evaluated. STS-treated proximal tubular epithelial cells exhibited enhanced viability at 10 °C compared with untreated control cells (p < 0.05). Also, STS and Hemopure improved renal graft function compared with control grafts (p < 0.05) in the early time period after the transplant, but long-term function did not reach significance. Overall, renal graft preservation at 10 °C with STS and Hemopure supplementation has the potential to enhance graft function and reduce kidney damage, suggesting a novel approach to reducing IRI and post-transplant complications.

Surgical strategy for orthotopic kidney transplantation.

Surgical strategy for orthotopic kidney transplantation.

Abstract 13671: A Case of Diffuse Alveolar Hemorrhage While on Systemic Anticoagulation for Impella

A 57 year old male with PMH of non-ischemic cardiomyopathy (EF 30%), atrial fibrillation, and VT s/p ICD was admitted to the cardiac intensive care unit for cardiogenic shock. His condition deteriorated necessitating Impella 5.5 implantation as bridge to cardiac transplant. Systemic heparin was started per Impella protocol with a lower anti-Xa goal of 0.2 - 0.3 given post-op bleeding at the R axillary Impella site. Five days post Impella placement he developed bloody secretions from the endotracheal tube requiring multiple blood transfusions and discontinuation of systemic heparin, while maintaining heparin purge. Labs were notable for anti-Xa 0.22, hemoglobin 9.7, and platelets 221. CT Chest demonstrated parenchymal opacities concerning for diffuse alveolar hemorrhage (DAH) which was confirmed via bronchoalveolar lavage; he had no known history of lung disease. High-dose corticosteroids were administered as a high ANA titer (1:128) and low C3 suggested capillaritis. However, decreasing ANA (1: 320) and a negative autoimmune workup decreased the likelihood of a rheumatologic cause for DAH and steroids were discontinued. DAH secondary to acquired von Willebrand syndrome (aVWS) was considered, but factor VIII and vWF activity levels were normal. The bloody secretions improved with inhaled thromboxane and systemic heparin was restarted. Orthotopic heart and kidney transplant was performed with subsequent Impella removal 104 days after Impella placement. Discussion: We present the first documented case of DAH with isolated Impella 5.5 support. Previously reported cases of DAH post-Impella were observed in patients with concurrent ECMO or RVAD. As autoimmune and coagulopathic causes of DAH were excluded, bland DAH secondary to systemic anticoagulation is most likely in this case. This raises a question about how to balance the risk of bleeding with the risk of device thrombosis, stroke and embolic events and when to switch from heparin to sodium bicarbonate purge.

Simultaneous heart and kidney transplantation: Our first experience

The gold standard treatment for end-stage heart and kidney failure is simultaneous heart and kidney transplantation. The global number of recipients on the waiting list and performed organ transplants increases annually. However, there is a lack of well-defined selection criteria for multi-organ transplants, leading to variations based on geographic region and local protocols.&#x0D; In this study, we present our initial experience with simultaneous heart and kidney transplantation in Patient P, a 51-year-old individual with severe calcification of the mitral valve and end-stage chronic kidney disease. Surgical correction was not possible, and thus the patient underwent orthotopic simultaneous heart and kidney transplantation. During the early postoperative period, the patient experienced acute renal failure in the transplanted kidney, which was managed through courses of hemodialysis.&#x0D; The findings of this clinical observation represent the first experience of multi-organ transplantation in Ukraine. Our clinical observation illustrates the successful feasibility of simultaneous orthotopic heart and kidney transplantation, showcasing promising immediate and medium-term follow-up results.

VE11 - Orthotopic robot-assisted kidney transplantation: Step-by-step

VE11 - Orthotopic robot-assisted kidney transplantation: Step-by-step

Kidney Autotransplantation and Orthotopic Kidney Transplantation: Two Different Approaches for Complex Cases.

Introduction Transplantation surgery teams often have to face complex cases. In certain circumstances, such as occlusion of the iliac vessels or prior pelvic surgery, heterotopic kidney transplantation may not be feasible and orthotopic kidney transplantation (OKT) could be a good alternative. Kidney autotransplantation (KAT) has been described as a potential treatment for complex renovascular, ureteral, or neoplastic conditions. There are scarce data regarding the complications and outcomes of these procedures; therefore, we present our experience. Materials and Methods We retrospectively analysed the medical records of both 21 patients who had received OKT and 19 patients who underwent KAT between 1993 and 2020. We collected demographic features and data regarding surgical technique, complications, and graft outcomes. Kidney graft survival was calculated using Kaplan–Meier survival analysis. Results Regarding OKT, in 15 (71.43%) cases, it was the first kidney transplantation. The most common indication was the unsuitable iliac region due to vascular abnormalities (57.14%). The early postoperative complication rate was high (66.67%), with 23.81% of Clavien grade 3b complications. During the follow-up period (mean 5.76 -SD 6.15- years), we detected 9 (42.85%) graft losses. At 1 year, the survival rate was 84.9%. Concerning KAT, the most frequent indication was ureteral pathology (52.63%), followed by vascular lesions (42.11%). The overall early complication rate was 42.11%. During the follow-up period (mean of 4.47 years), 4 (15.79%) graft losses were reported. Conclusions Although OKT and KAT have high complication rates, these techniques can be considered as two valuable approaches for complex cases, in the absence of other therapeutic options.

Bone Marrow Mesenchymal Stem Cells (BMSCs)-Exosomes Carrying MicroRNA-965 Attenuates Allogeneic Renal Transplant Rejection Through Regulation of Janus Kinase/Signal Transducers and Activators of Transcription 3 (JAK/STAT3)

This study intends to evaluate the potential effect of BMSC-derived exosomes (exo) on the rejection of allogeneic kidney transplantation in a rat model. BMSCs were cultured and their exos were collected for characterization, in which the expression of miR-965 was detected by PCR. Rats received orthotopic kidney transplantation and treated with exos or PBS followed by analysis of serum creatinine and BUN, inflammatory cell infiltration, renal fibrosis and vascular wall fibrosis by immunohistochemistry staining, JAK2/STAT3 phosphorylation by Western-blot, the inflammatory factor level by ELISA kit, and CD4+ cells differentiation by flow cytometry. miR-965 was enriched in BMSC-derived exo. Treatment with exo ameliorated the allograft rejection, improved renal function, and reduced the histological changes of kidney. In addition, exosomal treatment decreased the level of serum inflammatory cytokines, and altered T cell subpopulations. Meanwhile, fibrosis and neointima formation was reduced as demonstrated by related protein expression and signaling pathways was inactivated in the presence of exos. In conclusion, the miR-965 derived from BMSC-exos mitigated the renal allograft rejection through JAK/STAT3 signaling.

Orthotopic kidney transplantation survival and complications: systematic review and meta-analysis

ABSTRACT Purpose To determine graft and patient survival and adverse events in patients who undergo orthotopic kidney transplantation. Methods We performed a systematic review and meta-analysis. We search in Medline, Embase, and Central from inception to nowadays. We included observational studies with patients who undergo orthotopic kidney transplantation. The primary outcomes were overall patient and graft survival. We pooled the information in a frequency meta-analysis with a 95% CI. We analyzed bias with the STROBE statement. Results Of the 106 papers initially retrieved, four met the inclusion criteria. Vascular and urinary tract complications were reported in 19% and 15%, respectively. The overall patient survival was 92% 95%CI (88% to 95%), I2 = 0%, and the overall graft survival was 88% 95 CI (83% to 91%), I2 = 0%. Conclusion Our analysis showed a high survival rate in patients and kidney grafts after orthotopic kidney transplantation, with a similar complication rate compared to a heterotopic kidney transplant.

A1097 - Orthotopic kidney transplant: Transplantation beyond the iliac vessels

A1097 - Orthotopic kidney transplant: Transplantation beyond the iliac vessels

Simultaneous Orthotopic Liver and Orthotopic Kidney Transplantation: A Comparison with the Traditional Surgical Technique

Introduction: Simultaneous liver-kidney transplantation (SLKT) is performed by transplanting liver orthotopically and kidney heterotopically. We performed SLKT using another approach; simultaneous orthotopic liver and orthotopic kidney transplantation (SOLOKT), which has not been reported yet. We hypothesized that SOLOKT will lead to a shorter cold ischemia time (CIT) for kidney allograft, shorter ICU and hospital stay, and lower incidence of hematoma/fluid collection.

Combined Heart – Liver – Kidney Transplantation: A Pioneer Experience in South America

Multiorgan dysfunction is common in population with heart failure, particularly, hepatic dysfunction. A heart or liver transplantation procedure performed in isolation itself presents multiple challenges for the perioperative team. Accordingly, combining both transplants yields a vastly more complicated surgery, with many unique multisystem and multidisciplinary considerations. Although combined heart and liver transplantations are being performed with increasing frequency. Case report: Male patient, 56 years old, diagnosed with dilated cardiomyopathy with biventricular dysfunction and cardiac cirrhosis associated with cardiorenal syndrome. He evolved with progressive dyspnea, undergoing frequent paracentesis and hemodialysis, being listed for transplantation, which took place in April 2021. The uptake occurred in a single-piece block consisting of the heart and liver, with the kidneys removed afterwards. The procedure was performed using the block technique, with simultaneous heart and liver implants, with extracorporeal circulation. Orthotopic kidney transplantation occurred after completion of the other two implants. After surgery, the patient was referred to the intensive care unit, where he remained for 6 days and was discharged after 17 days. Hemodialysis was not necessary at any time after surgery. Conclusion: Due to the high morbidity and mortality rates of cardiac surgery in patients with liver cirrhosis, especially those with Child-Pugh C disease, the combined transplantation may be a promising. However, patients should be carefully selected for this complex procedure, especially in these times of organ shortages.

A Rat Model of Orthotopic Kidney Transplantation Based on Nonanastomotic Technique

Renal transplantation is an effective treatment for end-stage renal disease, which involves pathophysiologic processes such as ischemia-reperfusion injury and immune rejection. The degree of ischemia-reperfusion injury is closely related to the functional state of the transplanted kidney. At present, the allogeneic kidney transplantation model has been widely used in related research. The traditional kidney transplantation model has the disadvantages of complicated vascular anastomosis, difficulty in ureteral reconstruction. The aim of this study was to establish a rat autologous orthotopic kidney transplantation model based on non-anastomotic technique. Inbred Wistar rats weighing 260 to 280 g were selected. The rats were anesthetized by intraperitoneal injections of 40 mg/kg body weight pentobarbital sodium. We exposed and freed the left kidney after laparotomy and separated the left renal artery and left renal vein, abdominal aorta, and posterior vena cava. A purse-string suture with a diameter of 1 to 2 mm was made through the tunica media of the abdominal aorta. A puncture was made through the center of the purse-string suture. The in-dwelling needle was placed in the renal artery along the blood flow direction, and was infused with constant flow of 4°C heparinized lactated ringer's solution until the kidney became pale yellow. The renal vein was ligated and the renal artery was clamped. The in-dwelling needle was removed, purse-string suture was ligated, and the kidney was stored in a self-made autologous kidney transplant cold storage bag for 4 hours. We then opened the vein and artery, removed the cold storage bag, and rewarmed with 37°C normal saline. The abdomen was then closed layer by layer. Fifty-two orthotopic renal transplantations were performed, which included pre-experimental (40 operations) and experimental stages (12 operations). The success rates of the 2 stages were 75% and 91.7%, respectively. The main causes of failure were intraoperative hemorrhagic shock and postoperative infection. The operation time of orthotopic renal transplantation was 360 ± 30 minutes, including 30 ± 10 minutes for dissociation and management of kidney and blood vessels, 1 ± 0.5 minutes for warm ischemia and 240 ± 10 minutes for cold storage. Rats were sacrificed at 1 day and 7 day respectively. The rats were in good condition after operation. They could eat and drink freely. At 24 hours and 1 week after transplantation, the kidney's blood supply was good, the intestine was light or showed no adhesions, and the abdominal cavity had no ascites or peculiar smell. Hematoxylin & eosin (H&E) staining showed that there were no obvious pathologic changes in the sham group. The orthotopic kidney transplantation 1-day group showed pathologic changes of ischemia-reperfusion, such as swelling, necrosis, shedding, and cast formation of renal tubular cells. The orthotopic kidney transplantation 7-day group recovered well, with mild dilation of the renal capsule and mild dilatation of the renal tubules. The new model of autologous kidney transplantation is simple to use, does not require vascular anastomosis and ureteral reconstruction, and has a high success rate.

V02-02 ROBOTIC ORTHOTOPIC KIDNEY TRANSPLANTATION

You have accessJournal of UrologyMisc. Benign Disease & Transplant & Renovascular (V02)1 Sep 2021V02-02 ROBOTIC ORTHOTOPIC KIDNEY TRANSPLANTATION Francesc Vigués Julià, Begoña Etcheverry Giadrosich, Xavier Bonet Puntí, Natalia Picola Brau, Maria Fiol Riera, José Francisco Suárez Novo, and Lluis Riera Canals Francesc Vigués JuliàFrancesc Vigués Julià More articles by this author , Begoña Etcheverry GiadrosichBegoña Etcheverry Giadrosich More articles by this author , Xavier Bonet PuntíXavier Bonet Puntí More articles by this author , Natalia Picola BrauNatalia Picola Brau More articles by this author , Maria Fiol RieraMaria Fiol Riera More articles by this author , José Francisco Suárez NovoJosé Francisco Suárez Novo More articles by this author , and Lluis Riera CanalsLluis Riera Canals More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001979.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Orthotopic kidney transplant is a good alternative for patients with an end-stage renal disease non-suitable for a heterotopic kidney transplant (KT) due to severe iliac atherosclerosis or occupation of iliac fossa by previous grafts. This approach is performed through a left lumbotomy, using the splenic or renal artery, the renal vein and the native urinary tract. However, it is technically challenging and is associated with a higher rate of complications compared to conventional KT. Recently, robot-assisted kidney transplant (RAKT) has been shown to achieve excellent patient and graft outcomes, while reducing surgical morbidity. From the experience in RAKT, we have developed this technique in orthotopic transplantation. The aim of this video is to describe the technique of Orthotopic robotic assisted kidney (oRAKT). As far as we know, this is the first time described. METHODS: We present an oRAKT from a Controlled donor after cardiac death in a 65-year-old man with End-Stage Renal Disease non-suitable for a heterotopic KT due to severe iliac atherosclerosis and previously transplanted patient. RESULTS: Total surgical time was 324 min. The arterial and vein anastomoses time were 17 and 21 min respectively. A good renal reperfusion was observed after clamp removing. The estimated blood loss was 480 ml. A doppler ultrasound performed 24 hours after oRAKT showed a correct graft perfusion and the abdominal X-ray a correct catheter position. No postoperative complications were recorded. Pain was reported as minimal, no analgesic was required beyond 48h after surgery and the patient was discharged from the hospital at 9th day. The serum creatinine at the discharge day was 160 μmol/L. One year follow-up creatinine was 140 μmol/L. CONCLUSIONS: Orthotopic robotic assisted kidney transplant could provide a good minimally invasive alternative for selected patients non-suitable for a heterotopic KT and is technically feasible in centers with RAKT expertise. The potential advantages of the robotic approach are related to the reduction of lumbotomy morbidity, the better and more precise dissection of the native renal vein and splenic artery; and the more precise vascular anastomosis. Source of Funding: none © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e133-e133 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Francesc Vigués Julià More articles by this author Begoña Etcheverry Giadrosich More articles by this author Xavier Bonet Puntí More articles by this author Natalia Picola Brau More articles by this author Maria Fiol Riera More articles by this author José Francisco Suárez Novo More articles by this author Lluis Riera Canals More articles by this author Expand All Advertisement Loading ...

Laparoscopic Orthotopic Kidney Transplantation in Swine: A Novel Vascular Prop Device for Venous Anastomoses.

Objective: To investigate the safety and efficacy of a vascular prop device for laparoscopic orthotopic kidney transplantation (LOKT) in swine.Material and Methods: Twenty swine were randomly divided into two groups. A vascular prop device was used in the observation (VP) group, and the vein beltization technique was used in the control (VB) group. The right kidney, as a donor graft, was laparoscopically transplanted to the location of the left kidney after a left nephrectomy. Data on the operative time, venous anastomotic time, vein stenosis, etc., and the survival of the swine in the two groups were recorded.Results: The mean transplant operative time, the mean cold ischemia time, and the venous anastomotic times in the VP group were significantly shorter than those in the VB group. Seven swine in the VP group and three swine in the VB group survived for 7 days. Autopsy results showed the occurrence of one artery stenosis and one vein stenosis in the VP group and one artery stenosis and five vein stenoses in the VB group. The median survival time was 6.25 days for the swine in the VP group and 4.40 days for those in the VB group.Conclusions: The vascular prop device is safe and feasible for LOKT in swine and may accelerate venous anastomosis and ensure the quality of venous anastomotic stoma.

A controllable double-cycle cryogenic device inducing hypothermia for laparoscopic orthotopic kidney transplantation in swine.

BackgroundIt is necessity to maintain donor kidneys at a low temperature for laparoscopic orthotopic kidney transplantation (LOKT). We recently designed a controllable double-cycle cryogenic device (DCD) with a safer and more effective cooling setting. This study aimed to evaluate the safety and efficacy of this device in a swine model.MethodsA total of 20 pigs were procured for this study. We performed LOKT on 8 pigs using the controllable DCD for hypothermia, on another 8 pigs using the silicon tube cage (STC) for hypothermia, and on 4 pigs as the control group with no hypothermia measures (NH). The LOKTs were performed in autotransplantation mode in which the right kidney vein and artery were end-to-end anastomosed to the left kidney vein and artery in all three groups. The perioperative data, graft temperatures, and surgical complications were recorded, and histological examinations of kidney specimens were performed.ResultsThe average surface temperature in the DCD group (5±3.5 °C) was significantly lower than that in the STC (10±5.5 °C) and NH (28±3.0 °C) groups. In the DCD and STC groups, the temperature between the cooling setting and the adjacent peritoneum was 30±3.0 and 12±5.0 °C, respectively. All pigs survived for 7 days in the DCD group. In the STC group, 2 pigs died from liver lesions and other causes. A single pig had diabetes insipidus. No pigs survived for 7 days in the NH group. The specimens from pigs immediately after revascularization and from the surviving pigs on day 7 following transplantation showed that the morphology of the glomerular and renal tubules was largely normal in the DCD and STC groups. However, in the NH group, there was minimal interstitial and tubular oedema, and endothelial cell swelling occurred in some specimens immediately after revascularization. Pathological examination of the harvested graft specimens showed severe acute tubular necrosis in the NH group.ConclusionsThe newly designed controllable DCD can achieve the goal of cooling the kidney and warming the patient and may be a reliable, effective, inexpensive, and practical hypothermic maintenance system for LOKT in swine.

V62 - Orthotopic robot-assisted kidney transplantation

V62 - Orthotopic robot-assisted kidney transplantation

Simultaneous right-sided nephrectomy with orthotopic liver and kidney transplantation\u2014An alternative method for patients with autosomal dominant polycystic liver and kidney disease

PurposeIn patients suffering from autosomal dominant polycystic liver and kidney disease (ADPLKD), combined organ transplantation often poses a technical challenge due to the large volume of both organs. To simplify the transplantation procedure by improving the exposure of anatomical structures, we introduce a novel surgical technique of orthotopic liver and kidney transplantation.MethodsThe modified simultaneous liver and kidney transplantation technique via a right-sided L-incision included three steps: (1) right-sided nephrectomy in the recipient followed by (2) orthotopic liver transplantation in cava replacement technique and (3) the orthotopic kidney transplantation with arterial reconstruction to the right common iliac artery.ResultsIn total, seven patients with ADPLKD were transplanted by using the modified transplantation technique. The mean operation time was 342.43 min (±68.77). Postoperative patients were treated for 6.28 days (±2.50) in the intensive care unit and were discharged from the surgical ward approximately 28 days (±5.66) after the operation with normal graft function. Complications associated with the use of the modified technique, such as bleeding, anastomotic stenosis, biloma, or urinoma, did not occur.ConclusionModified simultaneous liver and kidney transplantation is a safe alternative for patients with ADPLKD. By combining right-sided nephrectomy and orthotopic graft transplantation, the approach optimizes the exposure of anatomical structures and simplifies the transplantation procedure. Additionally, the modified transplantation technique does not require a particular organ explantation procedure and can be applied for all liver and kidney grafts.

Klotho Regulates Epithelial-to-Mesenchymal Transition In Vitro via Wnt/β-Catenin Pathway and Attenuates Chronic Allograft Dysfunction in a Rat Renal Transplant Model.

BackgroundKlotho deficiency has been implicated in various kidney diseases and has been associated with renal fibrosis. However, the role of Klotho in renal allograft fibrosis still remains undetermined.Material/MethodsA 24-week-old rat renal transplant model with chronic allograft dysfunction (CAD) was carried out by orthotopic kidney transplantation using F344 donor rats to Lewis recipient rats. Successful establishment of the model was verified by HE and Masson staining and renal allograft function assessment. HK-2 cells were cultured and treated with TGF-β1 and/or siRNA-Klotho at various time points. Total proteins and RNA were extracted from the cultured cells and kidney tissues. Western blot assay and quantitative RT-PCR were used to analyze the expression of Klotho, fibronectin, and β-catenin pathways.ResultsWe successfully established and identified a 24-week-old rat renal transplant model with CAD. Loss of Klotho was identified to be associated with epithelial-to-mesenchymal transition (EMT), renal allograft fibrosis, and CAD. In HK-2 cells, a significant decrease of Klotho protein was observed in the renal fibrosis induced by TGF-β1 in a time-dependent manner. Moreover, intervention of siRNA-Klotho remarkably promoted the progression of renal fibrosis and activation of the Wnt/β-catenin signaling pathway.ConclusionsOur results show that Klotho has a significant protective role against EMT, renal allograft fibrosis, and CAD following kidney transplantation, which is mediated by inhibition of the Wnt/β-catenin signaling pathway.

Follicular T cells mediate donor-specific antibody and rejection after solid organ transplantation.

Following solid organ transplantation, a substantial proportion of chronic allograft loss is attributed to the formation of donor-specific antibodies (DSAs) and antibody-mediated rejection (AbMR). The frequency and phenotype of T follicular helper (Tfh) and T follicular regulatory (Tfr) cells is altered in the setting of kidney transplantation, particularly in patients who develop AbMR. However, the roles of Tfh and Tfr cells in AbMR after solid organ transplantation is unclear. We developed mouse models to inducibly and potently perturb Tfh and Tfr cells to assess the roles of these cells in the development of DSA and AbMR. We found that Tfh cells are required for both de novo DSA responses as well as augmentation of DSA following presensitization. Using orthotopic allogeneic kidney transplantation models, we found that deletion of Tfh cells at the time of transplantation resulted in less severe transplant rejection. Furthermore, using inducible Tfr cell deletion strategies we found that Tfr cells inhibit de novo DSA formation but only have a minor role in controlling kidney transplant rejection. These studies demonstrate that Tfh cells promote, whereas Tfr cells inhibit, DSA to control rejection after kidney transplantation. Therefore, targeting these cells represent a new therapeutic strategy to prevent and treat AbMR.