Establishment of a pig model of combined pancreas-kidney transplantation

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Simultaneous pancreas-kidney transplantation with modified enteric drainage of exocrine pancreatic secretion

BACKGROUND: As a valid therapeutic option for patients with type 1 diabetes mellitus (IDDM) and secondary dia- betic nephropathy, simultaneous pancreas-kidney trans- plantation (SPK) remains more undeveloped than other solid organ transplantations due to the restrictions of surgi- cal techniques especially the modes of exocrine pancreatic secretion. The aim of this paper was to summarize our sin- gle-center experience in SPK with modified enteric drai- nage (ED). METHODS: From June 2000 to July 2003, 10 patients with IDDM associated with uremia received SPK. The pancrea- tic allograft exocrine secretion was drained into the proxi- mal jejunum via a side-to-side duodenojejunostomy with- out Roux-en-Y anastomosis. Quadruple immunosuppres- sive regimen consisted of induction of tacrolimus (TAC) / cyclosporine (CsA), mycophenolate mofetil (MMF), ste- roids and antibodies, which included antilymphocyte glo- bulin (ALG) or anti-CD25 monoclonal antibody. RESULTS: ED-SPK without Roux-en-Y anastomosis was successful in all 10 patients without serious complications such as pancreatitis, graft thrombosis and pancreatic fistu- la. The patients regained immediate kidney allograft func- tion and euglycemia with insulin-independence. Four pa- tients survived over one year. Episodes of acute rejection were observed in 4 patients, 3 of whom showed reversion after treatment of OKT3 or insulin. Early postoperative complications included peritoneal infection ( 2 patients ), wound infection (2) and renal hematoma (1). CONCLUSION: ED-SPK without Roux-en-Y anastomosis is safe and preferable to the patients with IDDM associated with uremia.

DIFFERENCE OF REJECTION IN SINGLE VERSUS COMBINED PANCREAS AND KIDNEY TRANSPLANTATION IN RATS

Objective.To investigate the difference of rejection in single versus combined pancreas and kidney transplantation in rats. Methods.Allograft models including simultaneous pancreas and kidney(SPK)transplant and pancreas or kidney transplant alone were established in SD-Wistar rats, rejections of pancreas and kidney in different models were compared morphologically and functionally. Results.Mean survival time(MST)of pancreas was significantly prolonged in SPK than in pancreas transplant alone(PTA)(115 days vs. 92 days, P<005). Incidence of interstitial pancreatic rejection at grade Ⅱ and grade Ⅲ was much obvious in PTA than in SPK(429% vs. 125% at grade Ⅱ and 286% vs 63% at grade Ⅲ , P<005). No significant difference was found in MST between SPK and kidney transplant alone(KTA). Administration of cyclosporine A prolonged the MST of pancreas and kidney, without altering the tendency stated above. Conclusions.In SPK, the function of pancreas is protected by kidney hence the severity of rejection is reduced, whereas the function of kidney is not protected by pancreas. It suggests that different organs differ in immunoallergization and immunoregulation, and immune response tend to attack organs with greater immunoactivity, those organs with minor one could be protected. Cyclosporine A is effective on prolonging the MST of pancreas and kidney.

Establishment of simultaneous pancreas and kidney transplantation (SPK) model with cuff technique and portal venous drainage in rats

To establish a simultaneous pancreas and kidney transplantation （SPK） model in the rat. Methods： SD rats served as donors and recipients. The donor portal vein and the recipient superior mesenteric vein were anastomosed and the donor renal veins and recipient renal veins were anastomosed by cuff method. Arterial reconstruction was carried out by end to side anastomosis of the donor abdominal aorta to the recipient abdominal aorta. Enteric drainage was performed by side to side anastomosis between donors＇ duodenum and recipients＇ jejunum. The donor ureter -bladder valve was anastomosed to the bladder of recipients. Results： Out of 30 cases of SPK transplantation, 24 had normal serum glucose and serum creatinine after operation. The successful rate was 80 %. Conclusion： This model of SPK in rats is stable and reliable, which could be applied for further scientific research.

Early rejection and pathological changes in combined pancreaticoduodenal and kidney allotransplantation in pigs

Objective: To study the markers of early rejection and pathological changes in simultaneous pancreati- coduodenal and kidney transplantation (SPKT). Methods: Thirty hybrid pigs were used as donors and recipients. A renoportal end-to-end anastomosis be- tween the left renal vein and the distal end of the portal vein was performed. Two vascular end-to-side anastomoses between the donor portal vein and recip- ient inferior vena cava, and between the donor aortic segment including the celiac and superior mesenteric, and left renal arteries and recipient abdominal aorta were carried out. Pancreas exocrine secretion drain- age was established with duodenocystostomy. Ureter- ostomosis of the graft was performed. Urine amylase level, fasting blood glucose and urine volumes of kid- ney allograft were monitored, and pathological chan- ges of graft were observed. Results: Of 15 recipients, 2 died of disturbance of in- ternal environment and anastomotic bleeding, re- spectively. Satisfactory results were obtained in the remaining 13 recipients. The changes of urine amyl- ase concentration were prior to those of fasting blood glucose and urine volumes of kidney allograft. The degree of rejection of the kidney allograft was more severe than that of the pancreas and duodenum al- lograft. Conclusions: Urine amylase is the early marker of a- cute rejection in SPKT with bladder drainage of pan- creatic exocrine secretion. The pathological change of kidney allograft is most significant in SPKT.

What's new in clinical solid organ transplantation by 2013

Innovative and exciting advances in the clinical science in solid organ transplantation continuously realize as the results of studies, clinical trials, international conferences, consensus conferences, new technologies and discoveries. This review will address to the full spectrum of news in transplantation, that verified by 2013. The key areas covered are the transplantation activity, with particular regards to the donors, the news for solid organs such as kidney, pancreas, liver, heart and lung, the news in immunosuppressive therapies, the news in the field of tolerance and some of the main complications following transplantation as infections and cancers. The period of time covered by the study starts from the international meetings held in 2012, whose results were published in 2013, up to the 2013 meetings, conferences and consensus published in the first months of 2014. In particular for every organ, the trends in numbers and survival have been reviewed as well as the most relevant problems such as organ preservation, ischemia reperfusion injuries, and rejections with particular regards to the antibody mediated rejection that involves all solid organs. The new drugs and strategies applied in organ transplantation have been divided into new way of using old drugs or strategies and drugs new not yet on the market, but on phase Ⅰto Ⅲ of clinical studies and trials.

Machine perfusion in abdominal organ transplantation: Current use in the Netherlands

Scarcity of donor organs and the increment in patients awaiting a transplant increased the use of organs from expanded criteria donors or donation after circulatory death.Due to the suboptimal outcomes of these donor organs,there is an increased interest in better preservation methods,such as ex vivo machine perfusion or abdominal regional perfusion to improve outcomes.This state-ofthe-art review aims to discuss the available types of perfusion techniques,its potential benefits and the available evidence in kidney,liver and pancreas transplantation.Additionally,translational steps from animal models towards clinical studies will be described,as well as its application to clinical practice,with the focus on the Netherlands.Despite the lack of evidence from randomized controlled trials,currently available data suggest especially beneficial effects of normothermic regional perfusion on biliary complications and ischemic cholangiopathy after liver transplantation.For ex vivo machine perfusion in kidney transplantation,hypothermic machine perfusion has proven to be beneficial over static cold storage in a randomized controlled trial,while normothermic machine perfusion is currently under investigation.For ex vivo machine perfusion in liver transplantation,normothermic machine perfusion has proven to reduce discard rates and early allograft dysfunction.In response to clinical studies,hypothermic machine perfusion for deceased donor kidneys has already been implemented as standard of care in the Netherlands.

Parvovirus B19 status in liver,kidney and pancreas transplant candidates:A single center experience

BACKGROUND Parvovirus B19(B19V)is associated with a wide range of clinical manifestations.The major presentation is erythema infectiosum.However,a persistent infection may cause pure red cell aplasia and chronic anemia in immunocompromized patients.The B19V seroprevalence varies with age and geographical location.AIM To determine the B19V serological status and DNAemia in kidney,liver,and pancreas transplant candidates.METHODS Patients who underwent kidney,liver,or simultaneous kidney and pancreas/liver transplantation between January 2021 and May 2022 were included in the study.The serum samples were collected before transplantation.For detection of B19V DNA,a LightMix Kit B19V EC(TIB MOLBIOL,Berlin,Germany)was used.B19V IgM and IgG antibodies were detected using a commercial ELISA test(Euroimmun,Lübeck,Germany).RESULTS One hundred and thirty-one transplant candidates were included in the study,71.0%male,with an average age of 53.27 years±12.71 years.There were 68.7%liver,27.5%kidney,3.0%simultaneous pancreas/kidney transplant(SPKT),and 0.8%simultaneous liver/kidney transplant recipients.No patients had detectable B19V DNA.B19V IgG seroprevalence was 77.1%.No acute or recent infections were detected(IgM antibodies).There was no difference in the mean age of seronegative and seropositive patients(51.8 years±12.9 years vs 53.7 years±12.7 years,t=-0.603;P=0.548).Although seropositivity was lower in patients aged less than 30 years(66.6%)compared to the patients aged 30-59 years and>60 years(80.4%and 78.1%,respectively),this difference was not significant.In addition,there was no difference in seropositivity between male and female transplant candidates,76.3%and 78.9%(χ^(2)=0.104;P=0.748).The seroprevalence did not differ among organ recipients,with 77.8%,80.6%,and 50.0%for liver,kidney,and SPKT,respectively,(χ^(2)=5.297;P=0.151).No significant difference was found in the seroprevalence in kidney transplant patients according to dialysis modality.Seroprevalence was 71.1%in hemodialysis patients,and 100%in peritoneal dialysis patients(χ^(2)=0.799;P=0.372).CONCLUSION The B19V seroprevalence is expectedly high among kidney,liver,and pancreas transplant candidates,but there are still 22.9%of seronegative individuals who remain at risk for primary disease and severe manifestations.Further research should elucidate the necessity of B19V screening in peri-transplant management.

Mortality assessment for pancreas transplants in the United States over the decade 2008-2018

BACKGROUND Pancreas transplant is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes.However,since 2005,no comprehensive analysis has compared survival outcomes of:(1)Simultaneous pancreas-kidney(SPK)transplant;(2)Pancreas after kidney(PAK)transplant;and(3)Pancreas transplant alone(PTA)to waitlist survival.AIM To explore the outcomes of pancreas transplants in the United States during the decade 2008-2018.METHODS Our study utilized the United Network for Organ Sharing Standard Transplant Analysis and Research file.Pre-and post-transplant recipient and waitlist characteristics and the most recent recipient transplant and mortality status were used.We included all patients with type I diabetes listed for pancreas or kidneypancreas transplant between May 31,2008 and May 31,2018.Patients were grouped into one of three transplant types:SPK,PAK,or PTA.RESULTS The adjusted Cox proportional hazards models comparing survival between transplanted and non-transplanted patients in each transplant type group showed that patients who underwent an SPK transplant exhibited a significantly reduced hazard of mortality[hazard ratio(HR)=0.21,95%confidence intervals(CI):0.19-0.25]compared to those not transplanted.Neither PAK transplanted patients(HR=1.68,95%CI:0.99-2.87)nor PTA patients(HR=1.01,95%CI:0.53-1.95)experienced significantly different hazards of mortality compared to patients who did not receive a transplant.CONCLUSION When assessing each of the three transplant types,only SPK transplant offered a survival advantage compared to patients on the waiting list.PKA and PTA transplanted patients demonstrated no significant differences compared to patients who did not receive a transplant.

EN BLOC TRANSPLATION OF KIDNEY AND WHOLE PANCREAS WITH A SEGMENT OF DUODENUM IN RATS

For meeting the clinic needs in simultaneous pancreas and kidney transplantation (SPK), we success-fully establish a syngeneic SPK transplatation model in Lewis rats. The results indicate that this model isfeasible with a 82. 6% successful rate of operation and a 69. 6% survival rate in the first postoperativeweek. In long-term survived rats, the blood supplies are well established, function of the grafts (pancreasand kidney) maintains normal. This model is suitable for theoretical reserach in SPK transplantation for itsreasonable physiology with pancreatic juice drained into intestine and reduced postoperative complications inurinary tract and carbohydrate metabolism.

MRI and magnetic resonance angiography in evaluating simultaneous pancreas-kidney transplantation

OBJECTIVE: To evaluate the value of magnetic resonance imaging (MRI) and three dimensional (3D) contrast magnetic resonance angiography (MRA) in the diagnosis of complications of simultaneous pancreas-kidney transplantation (SPKT), as confirmed by biopsy and digital subtraction angiography (DSA). METHODS: Five MR examinations of five patients were performed within 28 days to 2 years after surgery on GE 1.5T MR system. Imaging techniques included axial and sagittal chemical fat-suppressed T1-weighted image (T1WI) and T2-weighted image (T2WI), additional contrast axial or saggital chemical fat-suppressed T1WI were obtained after 3D contrast MRA for calculating the mean percentage of the parenchymal enhancement (MPPE) of the pancreas and kidney. 3D contrast MRA was performed with Smartprep technique. MRA data were analyzed with maximum intensity projection (MIP) and multi-planner reformat (MPR). RESULTS: In five cases of transplant pancreases, MRI found two normal pancreas grafts, one case of acute rejection, one case of chronic rejection with 70% fibrosis and one case of late pancreatitis. In five transplant kidneys, MRI detected four normal kidney grafts and one case of acute rejection with infarction. MPPE could distinguish infarction from other complications. 3D contrast MRA could display vascular complications of SPKT, such as stenosis or occlusion, aneurysm formation of transplanted vessels and narrowing at the site of anastomosis, as confirmed by DSA. CONCLUSION: With combined application of MRI and 3D contrast MRA, complications of SPKT can be clearly identified.

A retrospective monocenter review of simultaneous pancreaskidney transplantation with bladder drainage in China

Background Simultaneous pancreas-kidney transplantation （SPKT） frees the diabetic patient with end-stage nephropathy from dialysis and daily insulin injections.Herein,we review consecutive cases of SPKT with bladder drainage performed at our institution over an 8-year period.Methods The study population included 21 patients （16 males and 5 females） who underwent SPKT between September 2001 and September 2009.Seven patients had type-1 diabetes and 14 had type-2 diabetes.Nineteen patients were on dialysis at the time of transplantation.Donation after cardiac death donors were selected for SPKT.The mean human leukocyte antigen match was 2 （range 0-4）.SPKT was always performed using bladder drainage and vascular anastomoses to the systemic circulation.Immunosuppressive treatment consisted of anti-lymphocyte globulin induction followed by tacrolimus,mycophenolate mofetil,and prednisone.Results The mean hospital stay was 45.43 days.After a mean follow-up of 39.4 months,survival rates for patient,kidney,and pancreas were 76.2%,76.2%,and 66.7% at 1 year;76.2%,59.3%,and 55.6% at 5 years;and 57.1%,39.5%,and 41.7% at 8 years,respectively.Major complications included anastomotic leaks,reflux pancreatitis,and rejection.Six patients died from septic shock （n=3）,duodenal stump leak （1）,cardiac arrest （1）,or renal failure （1）.Eight kidney grafts were lost due to acute rejection （n=2）,chronic rejection （3）,and death with a functioning graft （3）.Pancreatic graft failure （9） was caused by thrombosis （n=1）,rejection （2）,duodenal stump leak （1）,and death with a functioning graft （5）.Concluslons SPKT is a valid therapeutic option for uremic diabetics although few hospitals in China can undertake SPKT.

移植胰腺病理学诊断标准及其进展

胰腺移植和胰肾联合移植是治疗1型糖尿病和部分2型糖尿病及其并发症导致的肾衰竭的最佳治疗方法。胰腺移植的类型主要包括同期胰肾联合移植(SPK)、肾移植后胰腺移植(PAK)和单纯胰腺移植(PTA)。在所有的胰腺移植类型中,对移植胰腺的活组织检查(活检)仍然是明确诊断其排斥反应并与其他并发症进行鉴别的最佳方法。本文对移植胰腺活检的方法及其相关的研究进展、移植胰腺活检排斥反应诊断标准及其进展、移植胰腺主要的并发症及其病理学表现进行阐述,旨在为指导临床对上述并发症予以准确诊断,良好地保障移植胰腺和受者的长期存活提供参考。