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.

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.

Pancreas transplantation in type Ⅱ diabetes mellitus

Although the diagnosis of type 2 diabetes mellitus was once considered a contraindication to simultaneous pancreas-kidney transplantation, a growing body of evidence has revealed that similar graft and patient survival can be achieved when compared to type 1 diabetes mellitus recipients. A cautious strategy regarding candidate selection may limit appropriate candidates from additional benefits in terms of quality of life and potential amelioration of secondary side effects of the disease process. Although our current understanding of the disease has changed, uniform listing characteristics to better define and study this population have limited available data and must be established.

Exocrine drainage in vascularized pancreas transplantation in the new millennium

The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980 s to 1995, most pancreas transplants were whole organ pancreatic grafts with insulin delivery to the iliac vein and diversion of the pancreatic ductal secretions to the urinary bladder(systemic-bladder technique). The advent of bladder drainage revolutionized the safety and improved the success of pancreas transplantation. However, starting in 1995, a seismic change occurred from bladder to bowel exocrine drainage coincident with improvements in immunosuppression, preservation techniques, diagnostic monitoring, general medical care, and the success and frequency of enteric conversion. In the new millennium, pancreas transplants are performed predominantly as pancreatico-duodenal grafts with enteric diversion of the pancreatic ductal secretions coupled with iliac vein provision of insulin(systemic-enteric technique) although the systemic-bladder technique endures as a preferred alternative in selected cases. In the early 1990 s, a novel technique of venous drainage into the superior mesenteric vein combined with bowel exocrine diversion(portal-enteric technique) was designed and subsequently refined over the next ≥ 20 years to recreate the natural physiology of the pancreas with firstpass hepatic processing of insulin. Enteric drainage usually refers to jejunal or ileal diversion of the exocrine secretions either with a primary enteric anastomosis or with an additional Roux limb. The portal-enteric technique has spawned a number of newer and revisited techniques of enteric exocrine drainage including duodenal or gastric diversion. Reports in the literature suggest no differences in pancreas transplant outcomes irrespective of type of either venous or exocrine diversion. The purpose of this review is to examine theliterature on exocrine drainage in the new millennium(the purported "enteric drainage" era) with special attention to technical variations and nuances in vascularized pancreas transplantation that have been proposed and studied in this time period.

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.

成功抢救2例高龄胰肾联合移植患者严重PRCA并发症

目的 探讨高龄胰肾联合移植病人免疫抑制低下与发生纯红细胞再障(PRCA)的关系。方法 1998年12月,5例胰肾移植患者中2例并发PRCA及自身免疫溶血性贫血,监测微小病毒B_(19),T_4/T_8比值及骨髓象。采用调整免疫抑制剂、抗病毒、输注红细胞等综合疗法。结果 2例PRCA患者分别于2周、3周骨髓象恢复正常,并观察1年以上无复发。结论 高龄、免疫力低下、微小病毒B_(19)感染、免疫抑制药物易诱发PRCA,临床综合治疗是有效措施。