Outcome of simultaneous kidney pancreas transplantation: a single center analysis

The aim of this study was to evaluate the outcome of simultaneous kidney pancreas transplantation (SKPT) by various surgical techniques. The 161 patients submitted to SKPT underwent the following: 36 pancreas with duct occlusion (from 1985 to 1989), 75 with whole pancreas with bladder diversion (from 1990 to 1998), and 50 whole pancreas with enteric diversion (40 with systemic and 10 with portal drainage) (from 1999 to September 2002). A positive effect on patient survival was evident using enteric diversion versus the duct occlusion group (P = .005), and versus the bladder diversion group (.035), and on pancreas graft survival in the enteric diversion versus the duct occlusion group (P < .028). These improvements may be due to refined donor and patient selection criteria, surgical technique, and immunosuppression.     

Cost–utility analysis of living-donor kidney transplantation followed by pancreas transplantation versus simultaneous pancreas–kidney transplantation

For a type I diabetic with end-stage renal disease, the choice between a kidney-alone transplant from a living-donor (KA–LD) and a simultaneous pancreas–kidney (SPK) transplant remains a difficult one. The prevailing practice seems to favor KA–LD over SPK, presumably due to the superior long-term renal graft survival in KA–LD and the elimination of the lengthy waiting time on the cadaver transplant list. In this study, two treatment options, KA–LD followed by pancreas-after-kidney (PAK) and SPK transplant, are compared using a cost–utility decision analysis model. The decision tree consisted of a choice between KA–LD+PAK and SPK. The analysis was based on a 5-yr model and the measures of outcome used in the model were cost, utility and cost–utility. The expected 5-yr cost was $277 638 for KA–LD+PAK and $288 466 for SPK. When adjusted for utilities, KA–LD+PAK at a cost of $153 911 was less cost-effective than SPK at a cost of $110 828 per quality-adjusted year. One-way sensitivity analyses were performed by varying patient and graft survival probabilities, utilities and cost. SPK remained the optimal strategy over KA–LD+PAK across all variations. Two-way sensitivity analysis showed that in order for KA–LD+PAK to be at least as cost-effective as SPK, 5-yr pancreas and patient survival rates following PAK would need to surpass 86 and 80%. In conclusion, according to the 5-yr cost–utility model presented in this study, KA–LD followed by PAK is less cost-effective than SPK as a treatment strategy for a type I diabetic with end-stage renal disease. For patients interested in the benefits of a pancreas transplant, it would be reasonable to offer SPK as the optimal treatment, even if a living kidney donor is available.     

Neoplasm incidence in simultaneous pancreas and kidney transplantation: a single-center analysis

Background

Long-term immunosuppression is associated with an increased rate of cancer. The aim of this study was to analyze the incidence of newly diagnosed tumors in simultaneous kidney and pancreas transplantation (SPKT).

Methods

We retrospectively analyzed the incidence of a neoplasm among 360 diabetic subjects who consecutively underwent SPKT from 1985 to August 2010 in a single institution. Data were retrieved from the institutional registry. We evaluated the nature of all newly diagnosed malignant tumors, including posttransplantation lymphoproliferative disease (PTLD), to compare Kaplan-Meier survival rates with those of patients free of a neoplasm.

Results

The median follow-up was 8 years; the overall 5-year patient survival was 84%. In 25 patients the tumors were malignant. Almost one-fourth of the cancers represented skin tumors (3 squamous cell and 4 basal cell carcinomas). PTLD was diagnosed in 5 recipients. The cumulative survival of patients with malignancies was significantly lower than that in recipients without cancer (8-year survival by 38% vs 70%; P < .001). The mean (±SD) time to diagnosis was 6 ± 3 years. Since 2004, the 12 recipients with malignancy who were switched to sirolimus at the time of diagnosis showed survivals that were not apparently better than those who remained on the established immunosuppression (46% vs 55%; P = .71).

Conclusions

The risk of neoplasm development was similar to that reported by other centers. Recipients of SPKT show higher incidence of cancer, though their overall survival is still significantly better than in those usually remaining on dialysis.     

Rescue therapy with tacrolimus in simultaneous pancreas/kidney transplantation

Abstract Tacrolimus has been effective both in primary and rescue therapy following steroid and OKT3-resistant acute rejection in liver and kidney transplantation. Due to the effects of tacrolimus on glucose metabolism, there has been concern about its use in simultaneous pancreas/kidney transplantation. We report on the results of six patients (three female, three male, age 35.2 ± 7.3 years) converted from cyclosporin A to tacrolimus following simultaneous pancreas/kidney transplantation in steroid-resistant acute rejection. Tacrolimus was induced 2.8 ± 1.7 months (range 1–4.8 months) after transplantation; follow-up was 3–18 months. Following conversion, creatinine levels declined in all patients [3.5 ± 1.2 mg/dl before conversion, 3.0 ± 1.9 mg/dl ( n = 6) at three months, 1.4 ± 0.1 mg/dl at 1 year (n = 3)]. Before conversion, fasting blood glucose levels averaged 154 ± 33 mg/dl, with three patients receiving insulin. Three months later no patient required insulin, the mean glucose level being 107 ± 23 mg/dl ( n = 6); at 1 year it was 92 ± 9 mg/dl ( n - 3). One patient lost his pancreatic graft after 4 months due to a mycotic aneurysm. We conclude that conversion to tacrolimus is a safe and effective treatment in cases of steroid-resistant rejections following pancreas/kidney transplantation.     

Rescue therapy with tacrolimus in simultaneous pancreas/kidney transplantation

Tacrolimus has been effective both in primary and rescue therapy following steroid and OKT3-resistant acute rejection in liver and kidney transplantation. Due to the effects of tacrolimus on glucose metabolism, there has been concern about its use in simultaneous pancreas/kidney transplantation. We report on the results of six patients (three female, three male, age 35.2 ± 7.3 years) converted from cyclosporin A to tacrolimus following simultaneous pancreas/kidney transplantation in steroid-resistant acute rejection. Tacrolimus was induced 2.8 ± 1.7 months (range 1–4.8 months) after transplantation; follow-up was 3–18 months. Following conversion, creatinine levels declined in all patients [3.5 ± 1.2 mg/dl before conversion, 3.0 ± 1.9 mg/dl (n = 6) at three months, 1.4 ± 0.1 mg/dl at 1 year (n = 3)]. Before conversion, fasting blood glucose levels averaged 154 ± 33 mg/dl, with three patients receiving insulin. Three months later no patient required insulin, the mean glucose level being 107 ± 23 mg/dl (n = 6); at 1 year it was 92 ± 9 mg/dl (n = 3). One patient lost his pancreatic graft after 4 months due to a mycotic aneurysm. We conclude that conversion to tacrolimus is a safe and effective treatment in cases of steroid-resistant rejections following pancreas/kidney transplantation.     

Toxoplasmosis after a simultaneous pancreas and kidney transplantation

We report the case of a simultaneous kidney and pancreas transplant recipient who presented with vague neurologic symptoms 21 months following the surgery. Computed tomography, magnetic resonance imaging, and fundoscopy findings were normal. Serology titers for antitoxoplasmic antibodies were increased. This was an atypical presentation of toxoplasmosis in a simultaneous kidney and pancreas transplant patient.     

Outcomes after simultaneous kidney‐pancreas versus pancreas after kidney transplantation in the current era

Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1 year. Similarly, 1‐year graft survival for both organs was not different. At last follow‐up, uncensored and death‐censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times.     

Trends and perspectives in pancreas and simultaneous pancreas and kidney transplantation

Pancreas transplantation is still the best option to achieve normoglycaemia and insulin independence in patients with type I diabetes. As a result of improvements in surgical techniques, immunosuppression and patient selection, one year survival rates of 95, 83, and 88% for patient, pancreas, and kidney survival, respectively, are reported for patients with simultaneous pancreas and kidney transplantation. The main goals for the future are to reduce postoperative morbidity, to identify the relevant indications for single pancreas transplantation, to adopt the best surgical technique for individual patients' needs (bladder versus enteric drainage with or without portal venous delivery of insulin), and to develop immunosuppressive strategies with low nephrotoxic and diabetogenic potential.     

The long-term survival of simultaneous pancreas and kidney transplant with basiliximab induction therapy

Interleukin-2 receptor (IL2R) antibody has emerged as an attractive induction therapy for organ transplant. However, the long-term outcome of basiliximab induction in simultaneous pancreas and kidney (SPK) transplant remains speculative. We retrospectively analyzed the long-term survivals of 91 consecutive SPK recipients with basiliximab as induction, combination of steroid, tacrolimus (TAC) and mycophenolate acid (MFA)--either mycophenolate mofetil (MMF) or sodium mycophenolate (myfortic) as maintenance. At one, three, five, and seven-yr, the actual patient survival rate were 91.2%, 90.3%, 88.1%, and 88.2%, respectively; kidney graft survivals were 90.1%, 84.7%, 78.6%, and 70.6%, respectively; and pancreas graft survivals were 86.8%, 80.6%, 71.4%, and 58.8% respectively. There was a low incidence of rejection and CMV infection. Basiliximab induction with TAC, MFA, and steroid maintenance therapy can provide excellent long-term outcome for SPK recipients.     

Basiliximab-chimeric anti-IL2-R monoclonal antibody in pediatric liver transplantation: comparative study

Basiliximab is a monoclonal antibody that binds to the alpha subunit (CD(25)) of the interleukin-2 receptor of activated T lymphocytes. The advantage of basiliximab in organ transplantation is the reduce possibility to calcineurin inhibitor dosages to avoid nephrotoxicity. Basiliximab has significantly reduced the incidence of acute rejection (AR) in renal transplant recipients; however, the results are uncertain in liver transplantation (LT). The objective of this investigation was to assess the effect of basiliximab to prevent AR in the first 6 months after pediatric LT. From March 2000 to October 2001, 32 recipients of a primary orthotopic cadaveric or living donor LT were given basiliximab by intravenous bolus injection on the day of transplantation (day 0) and on day 4. Four children who received one dose were excluded from the study. The rate and the intensity of AR episodes, the incidence of chronic rejection, serum creatinine level, incidence of infections, adverse side effects, and daily oral dosage of cyclosporine (Neoral) to maintain the target blood level of 850 to 1000 mg/dL at C2, 2 hours after the administration, were analyzed in the remaining 28 recipients. Results were compared to those obtained from a matched historical group (n = 28) of similar age, weight, and hepatic diseases distribution. None of the analyzed parameters was statistically significant (P >.05) except for the daily oral dose of cyclosporine (7 to 13 mg/kg/dose, P <.05). In our series, the addition of basiliximab to the immunosuppressive therapy did not reduce the incidence of AR in pediatric LT.     

A technique for kidney retransplantation after simultaneous kidney pancreas transplantation

Isolated failure of the renal graft after simultaneous kidney-pancreas transplantation (SPK) is a rare but potential outcome. Many of these patients are candidates for kidney retransplantation. This paper describes a series of 3 patients who underwent successful kidney retransplantation after SPK. The operation was completed through an extraperitoneal incision without disruption of the pancreas graft or need for a transplant nephrectomy.     

胰肾联合移植术后的免疫抑制治疗

目的探讨胰肾一期联合移植(SPK)术后免疫抑制药物的合理应用。方法 2005年1月至2009年6月我中心完成9例SPK,其中男5例,女4例,均采用空肠引流方式。术后采用IL-2单克隆抗体诱导的四联免疫抑制方案:IL-2单克隆抗体(舒莱或赛尼哌)+他克莫司(FK506)+霉酚酸酯(MMF)+激素,并逐渐过渡至单用FK506维持治疗。回顾性分析以上9例患者围术期及长期随访情况。结果 9例手术均获得成功。除1例早期死亡外,其余8例患者术后1周内肌酐降至正常水平,术后停用胰岛素时间为(11.5±3.5)d,空腹血糖恢复至正常时间为(15.4±6.3)d。8例患者随访4～50个月,共发生移植肾急性排斥4例,1例患者在接受床边血液透析过程中并发心脑血管意外后家属放弃治疗,其余3例患者经抗胸腺细胞球蛋白(ATG)或激素冲击治疗后移植肾功能均逆转恢复,随访过程中未发现移植胰腺排斥。结论胰肾联合移植是治疗糖尿病合并终末期糖尿病肾病的有效方法,术后早期采用IL-2单克隆抗体诱导的四联免疫抑制方案并逐渐过渡至单用FK506维持治疗是安全的。     

Infectious disease complications of simultaneous pancreas kidney transplantation

BACKGROUND: Although technical success rate of simultaneous pancreas kidney (SPK) transplantation in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy has improved, morbidity remains high due to infection and rejection. The purpose of this study was to analyse infections encountered in our series of SPK transplants, using a restrictive antibiotic prophylaxis policy. METHODS: We reviewed all infectious diseases after 66 consecutive bladder-drained SPK transplantations in 64 IDDM patients with end-stage renal disease due to diabetic nephropathy. During follow-up, the perioperative antibiotic regimen was altered (from 5 days preemptive therapy with multiple drugs to 1 day prophylaxis with cefamandole), and long-term viral prophylaxis (high-dose aciclovir) was introduced. For post-operative urinary tract or opportunistic infection, no prophylaxis was given. RESULTS: Overall mean infection rate was 2.9 infections/ patient/year after a mean follow-up of 2.3 years. Surgical site infections (SSI) were seen in 30% of the patients, with Enterococci present in 47%. Logistic regression showed one day cefamandole prophylaxis to be associated with SSI, but there was no significant influence of SSI on either graft or patient survival. Forty-eight percent of all infections were lower urinary tract infections (UTI). There were 59 first UTIs (89%), probably related to long-term Foley catheter use, and 47 second UTIs (71%). Subsequent UTIs were not microbiologically related to first UTIs. Cytomegalovirus (10 patients) and other opportunistic agents did not cause mortality or graft loss. Five grafts were lost due to infection (SSI three times, post-transplant lymphoproliferative disease twice). Only one patient died because of infection (2%). CONCLUSIONS: Infectious diseases after SPK transplantation caused significant morbidity but did not influence either patient or graft survival. A change in prophylactic policy for both SSI as well as recurrent UTI, combined with earlier Foley removal, may lower incidences of these infections.      

Macrovascular disease after simultaneous pancreas and kidney transplantation

The objective of this study was to evaluate the outcome of simultaneous pancreas and kidney transplantation (SPK) with focus on cardiovascular mortality and morbidity in relation to graft function. From January 1985 through 1999, 87 SPK were performed in the unit. Sixty recipients were males, median age at diabetes onset 13 yr (1-40) and age at transplantation 39 yr (29-54). No case was lost to follow-up. Morbidity and mortality during median 8 yr of follow-up (range 1-15 yr) were recorded. Major macrovascular disease (MVD) was defined as myocardial infarction or sudden death (AMI), stroke or peripheral gangrene requiring amputation of leg, foot or fingers. At the evaluation, 26 of 87 patients (30%) had died, 19 after loss of the pancreas graft and 20 after loss of the kidney. MVD was the dominant cause of death. Non-lethal MVD had previously been recorded in 62%. Of the 61 patients alive, 22 had lost their pancreas graft and 12 the concomitant kidney. MVD had occurred in 32%. Whereas 89% of the concomitant kidneys functioned when the pancreas graft did so, only 37% of the kidneys functioned if the pancreas had been lost, p < 0.0001. The mortality rate was significantly higher among patients who lost both grafts (16/26) than in those who lost only the pancreas graft (3/15), p = 0.01. Progressive MVD is a major clinical problem for SPK transplant patients, particularly if the kidney fails.