The impact of functioning pancreas–kidney transplantation and pancreas alone transplantation on the lipid metabolism of statin‐naïve diabetic patients

Abstract: Objective: To compare the lipid profile (total cholesterol – TC, triglycerides – TG, high density lipoprotein cholesterol – HDL‐c, low density lipoprotein cholesterol – LDL‐c and non‐HDL cholesterol – NHDL‐c) of patients with functioning pancreas–kidney transplantation (PKT) or pancreas transplantation alone (PTA) after one (T1) and two yr (T2) following their pre‐transplantation data (T0). Methods: Fifty‐three type 1 diabetic patients underwent pancreas transplantation (42 PKT and 11 PTA) remaining euglycemic after transplantation were evaluated before and one and two yr after the procedures. They were using predominantly tacrolimus‐mycophenolate mofetil‐based immunosuppression and low glucocorticoid dose with systemic venous drainage of the pancreatic graft. None of them used hypolipidemic agents for economical reasons. Lipids were reported as means ± standard error of the mean. Data obtained in T0 were compared with T1 and T2 using ANOVA followed by Student’s t‐test. Results: TC, LDL‐c, NHDL‐c and TG were lower in T1 and T2 when compared with T0 (p < 0.05) in PKT, while no change was observed for HDL‐c (p > 0.05). PTA group showed no significant changes in lipids. Conclusion: In spite of the known side effects of tacrolimus‐based immunosuppression to lipids, our study with a statin‐naïve sample showed improvements (PKT) or stabilization (PTA) in the serum lipid profile after pancreas transplantation.     

The case for pancreas after kidney transplantation

Abstract:  Pancreas after kidney (PAK) transplantation has historically demonstrated inferior pancreas allograft survival compared to simultaneous pancreas and kidney (SPK) transplantation. Under our current immunosuppression protocol, we have noted excellent outcomes and rare immunological graft loss. The goal of this study was to compare pancreas allograft survival in PAK and SPK recipients using this regimen. This was a single center retrospective review of all SPK and PAK transplants performed between January 2003 and November 2007. All transplants were performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included induction with rabbit anti-thymocyte globulin (thymoglobulin), early steroid withdrawal, and maintenance with tacrolimus and sirolimus or mycophenolate mofetil. Study end points included graft and patient survival and immunosuppression related complications. Transplants included PAK 61 (30%) and SPK 142 (70%). One-yr patient survival was PAK 98% and SPK 95% (p = 0.44) and pancreas graft survival was PAK 95% and SPK 90% (p = 0.28). Acute cellular rejection was uncommon with 2% requiring treatment in each group. Survival for PAK using thymoglobulin induction, early steroid withdrawal and tacrolimus-based immunosuppression is at least comparable to SPK and should be pursued in the recipient with a potential living donor.     

Posttransplant donor-specific anti-HLA antibodies negatively impact pancreas transplantation outcome

During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancreas-kidney [SPK]) were followed for the detection of posttransplant anti-HLA antibodies. Forty patients (24%) developed anti-HLA antibodies, 26 (65%) had donor-specific antibodies (DSA; 61% anticlass 2) and 14 (35%) non-DSA (78.6% anticlass 1). More rejection episodes were observed in patients with positive anti-HLA antibodies than in patients without antibodies (42.5% vs. 11%; p = 0.001), with the highest incidence observed in DSA patients (53.8%). More severe rejections (according to rescue therapy) were observed in DSA patients compared to non-DSA (p < 0.05) or to negative patients (p < 0.001). Contrasting with the kidney, pancreas graft survival did not differ between patients with or without anti-HLA antibodies. On the contrary, pancreas and kidney survivals were significantly lower in DSA positive patients (75% for both organs) as compared to non-DSA positive patients (100% for pancreas and 92% for kidney) or to HLA-negative patients (91% for pancreas and 89% for kidney). Nontechnical pancreas and kidney graft failures were significantly higher in positive than in negative anti-HLA patients (32.5% vs. 11%; p < 0.01). Occurrence of posttransplant DSA was an independent risk factor for both pancreas and kidney survival (HR 3.2; p = 0.039) in diabetic transplant recipients.     

Growth of a nation part II: impact of recipient obesity on whole-organ pancreas transplantation

Obesity has reached epidemic proportions in the USA. Consequently, there is an increasing number of obese diabetic patients who would otherwise be appropriate candidates for pancreas transplantation (PTx). This is a retrospective study of all PTx performed at Indiana University between 2003 and 2009 (n = 308) comparing recipients with body mass index (BMI) < 25, 25-29.9, and ≥30 kg/m(2) Data included recipient and donor demographics, seven and 90-d graft loss, one-yr pancreas, kidney (for SPK only) and patient survival, causes of graft loss and death, peak amylase and lipase, length of stay, readmissions, complications, HbA1C, and c-peptide. Of the 308 PTx, 100 (32%) were overweight and 42 (14%) were obese. Obese recipients were older and more likely to be men. Donor demographics were similar. There was no difference in seven-d or 90-d graft loss, one-yr pancreas, kidney or patient survival, cause of graft loss or death, 30-d peak amylase or lipase, HbA1C, or C-peptide. The incidence of post-transplant technical, immunological and infectious complications was similar except for an increased incidence of cytomegalovirus infection in the obese group. Two recipients returned to insulin therapy despite normal C-peptide levels. Although technically challenging, PTx can be successful in select obese recipients with similar results compared to normal BMI recipients.     

Growth of a nation part I: impact of organ donor obesity on whole-organ pancreas transplantation

Obesity has reached epidemic proportions in the USA. Consequently, there are an increasing number of potential organ donors that are obese, but would otherwise be appropriate donors for pancreas transplantation (PTx). This is a retrospective study of all PTx performed at Indiana University between 2003 and 2009 (n = 308) comparing donors with body mass index (BMI) <25, 25-29.9, and ≥30 kg/m(2) . Data included recipient and donor demographics, seven and 90-d graft loss, one-yr pancreas, kidney (for simultaneous pancreas and kidney transplant only) and patient survival, causes of graft loss and death, peak amylase and lipase, length of stay, readmissions, complications, HbA1C, and c-peptide. Of the 308 donors, 84 (27%) were overweight and 43 (14%) were obese. The overweight donors were significantly older, and the obese donors had hypertension significantly more frequently than the other two groups. There were no significant differences in recipient transplant demographics. There was no significant difference in length of stay or 90-d readmissions, seven or 90-d pancreas graft loss, one-yr graft or patient survival, peak serum amylase or lipase, HbA1C, or c-peptide. The incidence of post-transplant technical, immunological, and infectious complications were similar. Although technically challenging, PTx of allografts from obese donors can be accomplished with similar results compared to normal BMI donors.     

The influence of socioeconomic deprivation on outcomes in pancreas transplantation

Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases including diabetes and renal failure, with poorer outcomes of their treatments. The influence of deprivation on outcomes following pancreas transplantation has not previously been reported. The Welsh Index of Multiple Deprivation was used to assess the influence of socioeconomic deprivation on outcomes for 119 consecutive pancreas transplant recipients from a single center in the United Kingdom, transplanted between 2004 and 2013. Outcomes measured were rate of acute rejection and graft survival. Thirty‐five (29.4%) patients experienced at least one episode of acute rejection following their transplant. Rejection rates in least deprived were 37% and most deprived 24% (p = 0.29). Within the individual domains, rejection rate was higher for the “physical environment” domain (least deprived 40% vs. most deprived 17% (p = 0.053). Five‐year graft survival for least and most deprived groups was 75% and 88%, respectively (log‐rank test p‐value 0.24). This study has not demonstrated any significant differences in outcomes following pancreas transplantation in Wales in relation to socioeconomic deprivation with the exception possibly of the “physical environment” domain. Further studies with larger patient population or concentrating on physical environment deprivation would be of interest.     

Effect of the surgical technique on long-term outcome of pancreas transplantation

To date there is no general consensus as to the best surgical technique for pancreas transplantation. Patients with a pancreas transplant functioning for 3 years or more were retrospectively investigated to compare three surgical techniques: segmental graft with duct obstruction (DO), whole graft with bladder drainage (BD), and whole graft with enteric drainage (ED). Several parameters were studied: patient and graft survival, rejection, long-term surgical and medical complications, and endocrine function. The best results in terms of graft survival and quality of metabolic control were obtained in the group that underwent whole graft transplantation with ED. At 3 years, overall pancreas graft survival was 65 % for ED, 60 % for BD, and 47 % for DO. This surgical method has become the preferred technique in our unit. Received: 9 October 1997 Received after revision: 29 January 1998 Accepted: 30 March 1998     

Review of immunosuppressive usage in pancreas transplantation

Throughout 1997, nearly 10 000 pancreas transplants have been performed worldwide, with 88% being simultaneous kidney transplants (SKPT). The current 1 yr patient survival rate exceeds 90% and pancreas graft survival (complete insulin independence) rate exceeds 80% for SKPT, 70% for sequential pancreas after kidney transplant (PAKT), and 65% for pancreas transplant alone (PTA). According to registry data, rejection accounts for 32% of graft failures in the first year after pancreas transplantation. However, improvements are expected to continue with the evolution of treatment protocols. Most pancreas transplant centers employ quadruple drug immunosuppression with anti-lymphocyte induction with either a monoclonal or polyclonal antibody agent. In recent years, there has been an overall decline in the use of antibody induction therapy from 90% during the period 1987–1993 to 83% of pancreas transplants performed during 1994–1997. Maintenance immunosuppression is triple therapy consisting of a calcineurin inhibitor (cyclosporine or tacrolimus), corticosteroids, and an anti-metabolite (AZA or MMF). Prior to 1995, nearly all pancreas transplant recipients were managed with Sandimmune. In the last 2 yr, tacrolimus-based therapy has been used in approximately 20% of cases and a new microemulsion formulation of cyclosporine (Neoral) has replaced Sandimmune in contemporary post-transplant immunosuppression. In addition, MMF is replacing AZA as part of the standard immunosuppressive regimen after pancreas transplantation. At present, a number of centers are conducting various trials with new drug combinations including either Neoral or tacrolimus in combination with steroids and MMF with or without antibody induction therapy. From 1994 to 1997, the 1 yr rates of immunologic graft loss have decreased to 2% after SKPT, 9% after PAKT, and 16% after PTA. The current array of new immunosuppressive agents are providing more effective control of rejection and permitting solitary pancreas transplantation to become an accepted treatment option in diabetic patients without advanced complications. The apparent potency of new drug combinations has also resulted in a resurgence of interest in steroid withdrawal. Immunosuppressive strategies will continue to evolve in order to achieve effective control of rejection while minimizing injury to the allograft and risk to the patient. In addition, new regimens must not only address the issue of specific drug toxicities but also long-term economic, metabolic, and quality of life outcomes. Pancreas transplantation will remain an important alternative in the treatment of diabetic patients until other strategies are developed that can provide equal glycemic control with less immunosuppression and overall morbidity.     

Early steroid withdrawal in solitary pancreas transplantation results in equivalent graft and patient survival compared with maintenance steroid therapy

Although steroid withdrawal in simultaneous kidney pancreas transplantation has been shown to be feasible, the results of early steroid withdrawal in immunologically solitary pancreas transplantation are not well known. This study evaluated an early steroid withdrawal protocol in this group. The results of steroid withdrawal at 21 d post-transplant in solitary pancreas transplant recipients was compared with a control group consisting of solitary pancreas transplant recipients maintained on steroids (MG). Additional immunosuppression consisted of rabbit anti-thymocyte globulin induction followed by tacrolimus and mycophenolate mofetil in both groups. The withdrawal group (WG, n = 22) consisted of 11 pancreas transplant alone (PTA), six pancreas after kidney (PAK), and five simultaneous cadaveric pancreas living kidney (SPLK) recipients. The steroid maintenance group (MG, n = 32) consisted of 8 PTA, 11 PAK, and 13 SPLK recipients. Recipient and donor demographic characteristics were similar. Seventy eight percent of MG patients had infection-related complications in the first year compared with 50% of the WG patients (p = 0.04). The one-yr rejection, pancreas graft, and patient survival rates were 27.3% 95.5%, and 100% in the WG, and 37.5%, 81.3%, and 93.8% in the MG respectively and not significantly different. We conclude that early corticosteroid withdrawal in isolated pancreas transplantation results in fewer infections and can be achieved without an increased risk of rejection or graft loss over the first year.     

Preservation of the donor pancreas for whole pancreas and islet transplantation

Ridgway D, Manas D, Shaw J, White S. Preservation of the donor pancreas for whole pancreas and islet transplantation.
Clin Transplant 2010: 24: 1–19. © 2009 John Wiley & Sons A/S.
Abstract:  Whole pancreas and islet cell transplantation are both reliant upon the procurement and preservation of a high quality donor pancreas for a successful outcome. In the climate of a reducing donor pool it is imperative that donor optimization, meticulous surgical retrieval and evidence based methods of preservation are practiced to ensure optimal graft quality. Moreover expanded criteria donors and novel methods of pancreas preservation have the potential to expand the number of usable grafts and increase the availability of these transplant modalities to suitable patients with diabetes. This article provides a review of the current literature surrounding donor management, surgical technique and the various technologies of organ preservation applicable to the donor pancreas.     

Duodenoduodenostomy in pancreas transplantation

Enteric drainage (ED) using duodenojejunostomy (DJ) is an established technique in pancreatic transplantation. Duodenoduodenostomy (DD), an alternative ED technique, may provide unique advantages over DJ. We compared our experience with these two types of ED through a retrospective review of all pancreas transplants performed at our institution from November 2007 to November 2009. The allograft duodenum was anastomosed to the recipient jejunum or duodenum. Duodenal drainage was performed by a stapled or hand-sewn technique. Patient demographics, operative times, major post-operative complications, and graft survival data were analyzed. Of 57 pancreas transplants, DJ was performed in 36 patients, stapled DD in 14 patients, and hand-sewn DD in seven patients. Two DD grafts (9.5%) thrombosed compared with no DJ grafts (p = NS). Enteric leak and small-bowel obstruction occurred in 3 of 36 DJ patients and in two DD patients (p = NS). Gastrointestinal bleeding occurred more frequently in stapled DD compared with DJ (4 vs. 0, p < 0.015). In conclusion, DD is technically feasible with no increase in operative time or enteric complications. GI bleeding rates appear to be higher following DD (stapled) technique. Potential complications of DD should be balanced against the benefits conferred by this technique.     

Initial experience using histidine-tryptophan-ketoglutarate solution in clinical pancreas transplantation

BACKGROUND: The colloid-based University of Wisconsin (UW) preservation solution has been used extensively in clinical pancreas transplantation. Experimental studies support the use of the crystalloid-based histidine-tryptophan-ketoglutarate (HTK) preservation solution for this purpose. AIM: We report our initial experience with HTK for pancreas allograft preservation and compare this to a contemporary experience with UW solution in conventional multiorgan deceased donors (<50 yr). MATERIALS AND METHODS: Retrospectively collected information on 33 pancreas transplants between September 2001 and October 2002 were analyzed for early graft function and complications up to 30 d after procurement and storage in either HTK or UW solutions. During multi-organ recovery, either UW solution (4-5 L) or HTK solution (8-10 L) was used for aortic perfusion and subsequent back-table flush and storage. Exocrine drainage of 31 pancreas allografts was enteric, while the bladder was used for drainage in two cases. Patient outcomes were analyzed according to the preservation solution used. Sixteen pancreata were used in combination with a kidney allograft (SPK), seven were used in patients after prior kidney transplantation (PAK), while 10 were used in patients who were not in renal failure (PTA). RESULTS: The UW group consisted of 17 patients (10 SPK, three PAK, four PTA) with a mean donor age of 29.5 +/- 10.7, and a mean cold ischemia time of 15.1 +/- 2.1 h. The mean post-transplant pancreas and kidney function on days 1 and 10 were amylase (315 and 99 IU/L), lipase (1727 and 346 IU/L), glucose (121 and 100 mg/dL) and creatinine (5.01 and 1.77 mg/dL). Patient and graft survival was 100% at 1-month post transplant. In the HTK group there were 16 patients (six SPK, four PAK, six PTA) with a mean donor age 21.9 +/- 5.7 and a mean cold ischemia time 14.0 +/- 1.3 h. The mean post-transplant pancreas and kidney function on days 1 and 10 were amylase (588 and 126 IU/L), lipase (4711 and 441 IU/L), glucose (97 and 109 mg/dL) and creatinine (5.28 and 2.42 mg/dL). Patient survival was 100% while graft survival was 94% at 1-month post-transplant. CONCLUSIONS: Early graft function and complications are comparable with HTK and UW solutions for pancreas allograft preservation.     

Octreotide administration in the treatment of pancreatic fistulae after pancreas transplantation

Among the surgical complications of pancreas transplantation are pancreatic fistulae, which arise rather frequently. Suppression of exocrine secretion with polymers has succeeded in reducing the rate of this complication. Nevertheless, in some instances, pancreatic fistulas may occur. Thirty pancreas transplantations were performed in 27 diabetic patients. In 5 cases a pancreatic fistula occurred and was drained after the insertion of a catheter for the collection of secretions. A serous liquid was collected with a high concentration of amylases (61604±19562 IU/24h). Fistula output was 280 ±87 ml/24 h. Patients were treated with octreotide, administered subcutaneously in a dose of 300–750 g/day. In all patients a progressive reduction in fistula output was observed after a mean of 16+2 days. Fistula flow rate dropped to 24±10 ml/24 h-areduction of 95%±5% and drainage was subsequently stopped. Sonographic followup did not show recurrence of peripancreatic collections in these patients. All patients were insulin-independent up to 12–44 months after surgery.     

Predictors of employment after liver transplantation

Employment after orthotopic liver transplantation (OLT) indicates recipients' physical/psychosocial adjustment. Our aim was to determine clinical, socioeconomic and health-related quality of life parameters influencing employment after OLT. Questionnaire on demographics, medical conditions, alcohol and drug use before/after OLT, and a validated 12-Item Short Form Health Survey (SF-12) were mailed to 126 adult OLT patients. Stepwise logistic regression was conducted to identify best predictors of post-OLT employment. Among non-retirees, 49% were employed after OLT. The predictors of employment were: employment status, income, disability status before OLT and Model of End Stage Liver Disease score. These variables had prediction rate of 82%. Individuals working during the five yr prior to OLT were likely to return to work (p<0.0001), particularly those who held a job for >6 months prior to OLT (p<0.0001), income>$80 000 before OLT compared with <$30 000 (p=0.036). Patients receiving Social Security Insurance (SSI) payment for >or=6 months prior to OLT, were less likely to work (p=0.0005). Severity/duration of liver dysfunction prior to OLT did not correlate with employment. Sense of physical health was poorer in those employed after OLT than in unemployed (p=0.0003). Socioeconomic factors were the most important predictors of post-OLT employment.     

Does combined kidney and pancreas transplantation reverse functional diabetic microangiopathy?

Abstract. Using videophotometric capillaroscopy and laser Doppler fluxmetry, we have investigated skin microvascular reactivity in the fingers of 14 diabetic patients with severe, late complications 20 months after combined kidney and pancreas transplantation. The results were compared with those obtained in 20 diabetic patients awaiting pancreas transplantation and in 19 healthy subjects. The capillary blood cell velocity at rest ( P < 0. 01) and during postocclusive reactive hyperemia ( P < 0. 05) was significantly lower in both patient groups than in the healthy controls. However, the time to peak capillary blood cell velocity during hyperemia was normal in the post-transplantation group (NS) but significantly prolonged in the pretransplantation group ( P < 0. 01). The ability to decrease flow during venous stasis-the so called venoarte-riolar reflex-was strongly impaired in the pretransplantation group ( P < 0. 001) but less so in the post-transplantation group ( P < 0. 05) as compared to healthy controls. It may be concluded that diabetic patients. after combined kidney and pancreas transplantation, show a tendency towards better microvascular reactivity than those awaiting transplantation.     

Current practices of donor pancreas allocation in the UK: future implications for pancreas and islet transplantation*

Recent refinements in technique mean islet cell transplantation offers the chance of a cure to an increasing patient cohort with diabetes. Such developments put pressure upon the scarce resource of donor organs, with potential competition between the modalities of cellular and solid organ transplantation. This questionnaire based study examines current patterns of donor pancreas procurement and use. Reasons for non procurement are studied together with the attitudes of transplant professionals to pancreas allocation. The minority of potentially useful pancreata are currently made available to either whole pancreas or islet transplant programs. Whilst professionals appreciate the role of each modality, there is a need to define criteria for pancreas allocation to avoid under use of donor organs.