Simultaneous pancreas-kidney transplantation for end-stage renal failure in type 1 diabetes mellitus: Current perspectives

Type 1 diabetes mellitus(T1DM)is one of the important causes of chronic kidney disease(CKD)and end-stage renal failure(ESRF).Even with the best available treatment options,management of T1DM poses significant challenges for clinicians across the world,especially when associated with CKD and ESRF.Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM.Simultaneous pancreas-kidney transplant(SPK)is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications.However,limited availability of the organs for transplantation,the need for long-term immunosuppression to prevent rejection,peri-and post-operative complications of SPK,lack of resources and the expertise for the procedure in many centers,and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe.This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.

PREVENTION AND TREATMENT OF REJECTION AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION

Objective To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney （SPK） transplantation. Methods Seventeen patients underwent SPK transplantation from September 1999 to September 2003 were reviewed retrospectively. Immunosuppression was achieved by a triple drug regimen consisting of cyclosporine, mycophenolate mofleil （MMF）, and steroids. Three patients were treated with anti-CD3 monoclone antibody （OKT3, 5 mg·d^-1） for induction therapy for a mean period of 5-7 days. One patients received IL-2 receptor antibodies （daclizumab） in a dose of I mg·kg^-1 on the day of transplant and the 5th day posttransplant. One patient was treated with both OKT3 and daclizumab for induction. Results No primary non-functionality of either kidney or pancreas occurred in this series of transplantations. Function of all the kidney grafts recovered within 2 to 4 days after transplantation. The level of serum creatinine was 94 ± 11 μmol/L on the 7th day posttransplant. One patient experienced the accelerated rejection, resulting in the resection of the pancreas and kidney grafts because of the failure of conservative therapy. The incidence of the first rejection episodes at 3 months was 47.1% （8/17）. Only the kidney was involved in 35.3% （6/17）; and both the pancreas and kidney were involved in 11.8% （2/17）. All these patients received a high-dose pulse of methylprednisone （0.5 g·d^-1） for 3 days. OKT3 （0.5 mg·d^-1） was administered for 7-10 days in two patients with both renal and pancreas rejection. All the grafts were successfully rescued. Conclusion Rejection, particularly acute rejection, is the major cause influencing graft function in SPK transplantation. Monitoring renal function and pancreas exocrine secretion, and reasonable application of immunosuppressants play important roles in the diagnosis and treatment of rejection.

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.

Simultaneous liver-kidney transplantation:Single-center study

Objective To analyze the curative effect of simultaneous liver and kidney transplantation ( SLKT) for patients with end - stage liver and kidney diseases and liver cirrhosis patients with hepatorenal syndrome. Methods All SLKTs ( n = 21) performed at our center from January 1999 to December 2010 were reviewed and

Alcohol associated liver disease and bariatric surgery:Current perspectives and future directions

Bariatric surgery is a routinely performed procedure and is associated with a reduction in all-cause mortality in patients with obesity.However,bariatric sur-gery has also been linked to increased alcohol use with up to 30%of these patients developing alcohol use disorder(AUD).The mechanism of AUD after bariatric surgery is multifactorial and includes anatomic,metabolic,and neurohumoral changes associated with post-surgical anatomy.These patients are at increased risk of alcohol associated liver disease and,in some cases,require liver trans-plantation.In this article,we provide a scoping review of epidemiology,patho-physiology,and clinical outcomes of alcohol-related health conditions after bariatric surgery.

Pancreas transplantation: The Wake Forest experience in the new millennium

AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant(SKPT) and solitary pancreas transplant(SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with my-cophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide. RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186(92%) were primary and 16(8%) pancreas retransplants; portalenteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American(AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels 】 2.0 ng/m L. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit antithymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient(86% SKPT vs 87% SPT) and kidney(74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates(both 65%) were similar(P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively(P 【 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients(P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a “type 2 diabetes” phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels.CONCLUSION: In the new millennium, acceptablemedium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.

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.

Simultaneous pancreas-kidney transplantation in a single center： 10-year retrospective analysis

Background Simultaneous pancreas-kidney transplantation （SPKT） is the best treatment option for diabetic patients with advanced chronic renal failure. The current study aimed to analyze the surgical indications, treatments and prognosis of SPKT.Methods We retrospectively analyzed 40 cases of SPKT performed between December 1999 and January 2010 in our center, including the survival rate, complications and the reasons of reoperation.Results Of all the 40 SPKT cases, the one-year survival rates of the recipients, kidney and pancreas transplant graft were 97.6%, 97.6% and 92.7%, while 97.6%, 91.1%, 92.7% at 3 years and 83.6%, 78.0%, 79.4% at 5 years, respectively. After SPKT, 10 patients need reoperation because of surgical complications （14 operations）. The reoperation rate was 25%, including 2 patients （4 operations） with hematuria, 4 patients with abdominal hemorrhage, 2 patients （3 operations） with abdominal infection, 1 patient with pancreatic venous thrombosis, 1 patient with anastomotic leakage, and 1 patient with fistula.Conclusion Although SPKT provides a successful and effective treatment for diabetics with end-stage renal disease, how to reduce the complications of this treatment still need further effort.