Effects of simultaneous pancreas-kidney transplantation and kidney transplantation alone on the outcome of peripheral vascular diseases.

BACKGROUND: The effects of Simultaneous Pancreas Kidney Transplantation (SPKT) on Peripheral Vascular Disease (PVD) warrants additional study and more target focus, since little is known about the mid- and long-term effects on the progression of PVD after transplantation. METHODS: 101 SPKT and 26 Kidney Transplantation Alone (KTA) recipients with insulin-dependent diabetes mellitus (IDDM) were retrospectively evaluated with regard to graft and metabolic outcome. Special subgroup analysis was directed towards the development and progression of peripheral vascular complications (PVC) (amputation, ischemic ulceration, lower extremity angioplasty/ bypass surgery) after transplantation. RESULTS: The 10-year patient survival was significantly higher in the SPKT group (SPKT: 82% versus KTA 40%; P < 0.001). KTA recipients had a higher prevalence of atherosclerotic risk factors, including coronary artery disease (P < 0.001), higher serum triglyceride levels (P = 0.049), higher systolic (P = 0.03) and diastolic (P = 0.02) blood pressure levels. The incidence of PVD before transplantation was comparable between both groups (P = 0.114). Risk factor adjusted multivariate analysis revealed that patients with SPKT had a significant lower amount (32%) of PVCs (32 PVCs in 21 out of 101 SPKT; P < 0.001) when compared to the KTA patients who developed a significant increase in PVCs to 69% of cases (18 PVCs in 11 out of 26 KTA; P < 0.001). In line mean values of HbA1c (P < 0.01) and serum triglycerides (P < 0.01) were significantly lower in patients with SPKT > 8 years after transplantation. CONCLUSION: SPKT favorably slows down development and progression of PVD by maintaining a superior metabolic vascular risk profile in patients with IDDM1.

Autoimmune Diabetes Recurrence After Pancreas Transplantation: Diagnosis, Management, and Literature Review.

BACKGROUND Pancreas transplantation can be a viable treatment option for patients with type 1 diabetes mellitus (T1DM), especially for those who are candidates for kidney transplantation. T1DM may rarely recur after pancreas transplantation, causing the loss of pancreatic graft. The aim of this study was to describe the prevalence of T1DM recurrence after pancreas transplantation in our series. MATERIAL AND METHODS Eighty-one patients transplanted from 2002 to 2015 were included. Autoantibody testing (GADA and IA-2) was performed before pancreas transplantation and during the follow-up. RESULTS The series includes 48 males and 33 females, mean age 37.4±5.7 years and mean duration of diabetes 25.5±6.5 years. Patients received simultaneous pancreas kidney (SPK) transplantation. After SPK transplantation, 56 patients retained pancreatic graft, 8 patients died, and 17 patients lost their pancreatic graft. T1DM recurrence occurred in 2 of the 81 transplanted patients, yielding a prevalence of 2.5%, with an average time of appearance of 3.3 years after transplant. Pancreatic enzymes were normal in the 2 patients, ruling out pancreatic rejection. T1DM recurrence was confirmed histologically, showing selective lymphoid infiltration of the pancreatic islets. CONCLUSIONS T1DM recurrence after pancreas transplantation is infrequent; however, it is one of the causes of pancreatic graft loss that should always be ruled out. Negative autoimmunity prior to transplantation does not ensure that T1DM does not recur.

Pancreas Transplantation from Donors after Circulatory Death: an Irrational Reluctance?

PURPOSE OF REVIEW: Beta-cell replacement is the best therapeutic option for patients with type 1 diabetes. Because of donor scarcity, more extended criteria donors are used for transplantation. Donation after circulatory death donors (DCD) are not commonly used for pancreas transplantation, because of the supposed higher risk of complications. This review gives an overview on the pathophysiology, risk factors, and outcome in DCD transplantation and discusses different preservation methods. RECENT FINDINGS: Studies on outcomes of DCD pancreata show similar results compared with those of donation after brain death (DBD), when accumulation of other risk factors is avoided. Hypothermic machine perfusion is shown to be a safe method to improve graft viability in experimental settings. DCD should not be the sole reason to decline a pancreas for transplantation. Adequate donor selection and improved preservation techniques can lead to enhanced pancreas utilization and outcome.

Influence of duration of type 1 diabetes on long-term pancreatic transplant outcomes.

BACKGROUND: There are no multicenter studies on the influence of diabetes duration on pancreatic transplant outcomes. Our study aimed to determine how type 1 diabetes duration influenced survival of pancreatic grafts. METHODS: The data of 8,139 patients who received pancreas transplants during 2006-2015 were extracted from the Scientific Registry of Transplant Recipients database. Patients were separated into two groups according to duration of diabetes: S group (diabetes ≤20 years) and L group (>20 years). RESULTS: Compared to S group, L group were older and prone to be male, to have higher body mass index, to receive pancreas after kidney transplantation (PAK), and to be White. Patient survival was not significantly different between the two groups, but pancreatic survival was better in the L group (hazard ratio 0.88; P = 0.012). Pancreatic survival of L group was better than S group in pancreas transplant alone and simultaneous pancreas-kidney transplantation (SPK). Graft survival was not significant different between the two groups in PAK. Diabetes duration was an independent predictor of graft survival in SPK patients (hazard ratio 0.86; P = 0.012). CONCLUSIONS: Diabetes duration has no influence on patient survival. However, long duration of type 1 diabetes mellitus appears to be protective against pancreatic graft loss.

Pancreas transplantation following total pancreatectomy for chronic pancreatitis.

BACKGROUND: Total pancreatectomy for chronic pancreatitis leads to brittle diabetes and challenging glycemic control with half of all patients experiencing severe hypoglycemia, many requiring medical intervention or hospitalization. Pancreas transplantation has the potential to manage both the endocrine and the exocrine insufficiency in this patient population. METHODS: Between June 1, 2005, and July 1, 2016, 8 patients with brittle diabetes following total pancreatectomy underwent pancreas transplantation. All grafts had systemic venous and enteric exocrine drainage. Data included demographics, graft and patient survival, pre- and post-transplant supplementation with pancreatic enzymes, and narcotic usage. RESULTS: Patient survival rate at 1 and 3 years was 88%. Pancreas graft survival rate of those alive at 1 year was 100% and 86%, respectively. About 75% of these patients remained insulin-free until their time of death, loss of follow-up, or present day. Of the patients with maintained graft function at 3 years, none required further hospitalization for glycemic control. About 75% of these patients have also maintained exocrine function without pancreatic enzyme supplementation. CONCLUSIONS: Pancreas transplant can treat both exocrine and endocrine insufficiency and give long-term insulin-free survival and should be considered as a viable treatment option for patients who have undergone total pancreatectomy for chronic pancreatitis.

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.

Contrast-enhanced ultrasound of the transplant pancreas in the post-operative setting.

BACKGROUND/OBJECTIVES: Vascular thrombosis is the most common cause of early graft loss after transplantation. Routine grayscale and Doppler ultrasound frequently fail to adequately visualize vascular compromise. Contrast-enhanced ultrasound is a novel approach to identifying these complications. METHODS: This was a prospective study of 22 consecutive patients who received pancreas transplant at our institution between 2017 and 2018. All allografts were implanted with systemic venous and enteric exocrine drainage. Perfusion was assessed in the immediate post-operative period using grayscale, Doppler, and contrast-enhanced ultrasound. Imaging findings were compared between those who required surgical re-intervention and those who did not in order to evaluate for differences in perfusion. RESULTS: Of the 22 transplants, 15 did not require surgical re-intervention and were considered normal. These allografts demonstrated prompt and uniform enhancement, with washout usually by 90 seconds. All patients who had abnormal CEUS underwent re-exploration. Perfusion was acceptable or restored in all cases. Two patients ultimately required allograft pancreatectomy. Two patients had normal glands, and the remaining 3 grafts were salvaged following intervention. CONCLUSIONS: Contrast-enhanced ultrasound provides rapid evaluation of allograft perfusion following pancreas transplantation. The differences in perfusion provide a novel way of evaluating for complications in the immediate post-transplant period.

Need for dental treatment in patients on the waiting list for liver and simultaneous pancreas-kidney transplant at a single center. / Necessidade de tratamento odontológico em pacientes candidatos a transplante simultâneo de pâncreas-rim e fígado num centro único.

OBJECTIVE: to evaluate the oral conditions and the main predisposing factors for dental treatment of patients on the waiting list for liver and simultaneous pancreas-kidney transplantation, in a single center. METHODS: we evaluated 100 patients in the waiting list, 50 candidates for liver transplantation and 50 for simultaneous kidney-pancreas transplantation, from August 2015 to February 2018. We correlated extra and intraoral examinations with pre-transplant demographic variables. RESULTS: the main oral alteration in the pancreas-kidney and liver transplant candidates were decayed, lost and filled teeth, present in 83% and 100% of the candidates, respectively (p=0.03). The need for dental treatment was equal in both groups: 71% and 70%. In liver transplant candidates, the predisposing factors for dental treatment were age, color and etiological diagnosis of liver cirrhosis. We did not identify predisposing factors for dental treatment in candidates for simultaneous pancreas-kidney transplant. CONCLUSION: candidates for liver and for simultaneous pancreas-kidney transplantation had poor oral hygiene, with cavities, residual roots, gingivitis and periodontitis, revealing that dental evaluation should be part of the transplantation waiting list.

OBJETIVO: avaliar as condições bucais e os principais fatores predisponentes para tratamento odontológico de pacientes em lista de espera para transplante simultâneo de pâncreas-rim e para transplante hepático, em um centro único. MÉTODOS: foram avaliados 100 pacientes na fila de espera, 50 candidatos a transplante hepático e 50 a transplante simultâneo de pâncreas-rim, no período de agosto de 2015 a fevereiro de 2018. Exames extra e intrabucais foram correlacionados com variáveis demográficas pré-transplante. RESULTADOS: a principal alteração bucal nos candidatos a transplante de pâncreas-rim e de transplante hepático foram dentes cariados, perdidos e obturados, presentes em 83% e 100% dos candidatos, respectivamente (P=0,03). A necessidade de tratamento odontológico foi igual nos dois grupos: 71% e 70%. Nos candidatos a transplante hepático, os fatores predisponentes para tratamento odontológico foram idade, cor e diagnóstico etiológico da cirrose hepática. Não identificamos fatores predisponentes para tratamento odontológico nos candidatos a transplante simultâneo pâncreas-rim. CONCLUSÃO: pacientes candidatos a transplante simultâneo de pâncreas-rim e transplante hepático apresentaram higiene bucal precária com presença de cárie, raízes residuais, gengivite e periodontite, revelando que a avaliação odontológica deve fazer parte do protocolo de atendimento dos pacientes em fila de espera para transplantes.

Preemptive Appendicectomy at the Time of Pancreas Transplantation: Is It Necessary?

OBJECTIVES: Pancreas transplant is a major intraabdominal operation, and in most cases the graft is placed in the rightiliac fossa. At our center, preemptive appendicectomy is performed at the time of pancreas transplant to prevent any future risk in a complex transplant patient. The aim of this study was to review all histology reports from the removed appendices. MATERIALS AND METHODS: The histology reports from all incidental appendicectomies performed at pancreas transplant were reviewed. RESULTS: Between January 2001 and June 2016, 107 pancreas transplants were performed (86 simultaneous pancreas and kidney transplants, 11 pancreas after kidney transplants, and 10 pancreas transplants alone), and 65 appendix histology reports were available from this patient group. All were preemptive appendicectomies as none of the patients had symptoms to suggest acute appendicitis. Of the 65 appendix histologies, 43 (66.2%) were reported as normal. Twenty specimens (30.8%) showed fibrosis consistent with previous inflammation of the appendix, and 12 specimens (18.5%) showed fecal material in the lumen (1 due to an obstructing fecalith and another 2 showing luminal distension with feces). Three specimens (4.6%) showed lymphoid hyperplasia. There were 5 (7.7 %) unexpected findings upon histology. In review of histology reports, 1 patient had a 1.1-mm carcinoid tumor in an otherwise normal appendix, 1 had an Enterobius species worm infestation, 1 had focal endometriosis, 1 had crypt abscesses suggestive of inflammatory bowel disease, 1 had a metaplastic polyp, and 1 had melanosis coli of unknown clinical significance. There were no cases of overt acute appendicitis. No patients experienced a complication as a direct result of their appendicectomy. CONCLUSIONS: A policy ofroutine appendicectomy atthe time of pancreas transplant appears to be justified and safe.

Sex matching does not impact the outcome after simultaneous pancreas-kidney transplantation.

BACKGROUND: Several studies in solid organ transplantation have shown a correlation between donor and recipient sex mismatch and risk of graft loss. In this study, we aimed to analyze the impact of donor and recipient sex matching on patient and pancreas graft survival in a large single-center cohort. METHODS: We retrospectively analyzed all first simultaneous pancreas-kidney transplants performed between 1979 and 2017 at the Medical University of Innsbruck. RESULTS: Of 452 patients, 54.6% (247) received a sex-matched transplant. Patient survival (P = .86), death-censored pancreas graft survival (dcPGS, P = .26), and death-censored kidney graft survival (dcKGS, P = .24) were similar between the sex-matched and sex-mismatched groups. Patient survival and dcPGS at 1, 5, and 15 years were 95.9%, 90.0%, and 62.1% and 86.1%, 77.1%, and 56.7% in the sex-matched group and 93.6%, 86.2%, and 62.4% and 83.1%, 73.3%, and 54.3% in the sex-mismatched group. Sex matching led to a lower odds of severe postoperative complications (41.2% vs 49.0%; OR 0.57, 95%CI 0.33-0.97; P = .038); however, no increased odds of other adverse postoperative outcomes was detected. CONCLUSION: Our study demonstrates that sex matching reduced the odds of postoperative complications but did not impact other early and late outcome parameters in our cohort.

Continuous glucose monitoring to assess glycemic control in the first 6 weeks after pancreas transplantation.

BACKGROUND: Current therapy for Type 1 diabetes (T1D) is characterized by significant glucose variability (GV). Pancreas transplantation (PT) is performed in certain T1D patients with and without end-stage renal disease. To date, GV has been examined to a limited extent after PT. METHODS: We investigated GV using continuous glucose monitoring (CGM) 3-6 weeks after PT. RESULTS: Eleven patients had simultaneous kidney pancreas transplantation (SPK), nine pancreas after kidney (PAK), and six pancreas transplantation alone (PTA). Mean CGM showed no difference between SPK, 126.5 ± 13.9, PAK 119.9 ± 12.8, and PTA 131.1 ± 29 mg/dL (P value .6). Percentage of time in range (TIR, 70-180 mg/dL) was 92% for SPK, 93.4% in PAK, and 88.5% in PTA with only 0.3%, 1.5%, and 0.3% of time <70 mg/dL. Percentage >180 mg/dL was 7.9% for SPK, 4.9% PAK, and 11% in PTA. Other measures of GV were similar in the three cohorts. In six patients, CGM was performed before and after PT and improved significantly. GV was also better compared with a matched cohort of T1D patients. CONCLUSIONS: All 3 types of PT resulted in excellent glucose control 3-6 weeks post-procedure. CGM outcomes represent an important objective outcome after PT.

Risk analysis of extended pancreas donor selection criteria.

INTRODUCTION: The success of pancreas transplantation, in combination with a stable number of available allografts has resulted in an increasing waiting list. This study investigated donor potential by expanding age and Body Mass Index (BMI) criteria. METHODS: All reported donors in the Netherlands between 2013 and 2017 were analysed. Risk assessment of extended criteria donors was done by in-depth analysis of donor reports and calculation of the Pancreas Donor Risk Index (PDRI). The PDRI of these extended criteria donors was compared to standard criteria donors to evaluate the increased risk on graft failure. RESULTS: A total of 1273 donors were reported. Of these donors, 405 donors were reported as pancreas donor, of which 93 (23%) pancreata were transplanted. Extending age criterion with 5 years could result in additional 40 Donation after Brain Death donors and 37 Donation after Circulatory Death donors reported. In 24 (31%) extended age criteria donors the PDRI was below the upper limit of currently transplanted pancreata. Extending BMI criteria to 35 kg/m2 could result in an additional 19 (6%) donors reported. CONCLUSIONS: Extending BMI criteria could result in a slight increase of reported donors. Extending age criteria increased significantly the number of reported donors. In 24 (31%) of the older donors the PDRI showed a reduced risk compared to currently transplanted pancreata. This study suggest that, if other risk factors are absent, pancreata of extended age and/or BMI criteria donors should be considered for transplantation.

Predictive factors of posttransplant glucose intolerance in Japanese patients with type 1 diabetes after pancreas transplantation.

Pancreas transplantation (PTx) has been performed worldwide for patients with type 1 diabetes accompanied with end-stage renal disease or uncontrollable glycemic fluctuation. Nevertheless, risk factors of posttransplant glucose intolerance, which is responsible for progress of diabetic complications, remains unclear, especially in cases without pancreatic graft function loss. Therefore, this study was conducted to search for predictive factors of future glucose tolerance in PTx recipients without pancreatic graft function loss. Subjects were selected from among 41 Japanese patients with type 1 diabetes who received PTx between 2000 and 2016 in Osaka University Hospital, and 24 subjects free from rejections and thromboses were analyzed. Several examinations to evaluate insulin secretion and insulin sensitivity within 6 months after transplantation (initial examination) were performed. Glucose tolerance was evaluated by 120-minute post-load plasma glucose level during 75-g oral glucose tolerance tests (OGTT), referred to as PGOGTT120, at the initial examination and between 1 year and 2 years posttransplantation (maintenance period). The initial examination factors that were correlated with PGOGTT120 in the maintenance period were PGOGTT120 [r = 0.52 (p = 0.01)], insulinogenic index [r = -0.65 (p < 0.01)], and the ratio of incremental area under the curve of insulin to that of plasma glucose (iAUCR) calculated from data of OGTT [r = -0.65 (p < 0.01)]. Insulinogenic index [ß = -0.28 (p = 0.02)] and iAUCR [ß = -0.29 (p = 0.02)] were still significantly correlated with PGOGTT120 in the maintenance period after adjustment for PGOGTT120 at the initial examination. In conclusion, insulinogenic index and iAUCR from OGTT performed in the early posttransplantation period were predictive factors of future glucose intolerance.

Association between Aortic Calcification, Cardiovascular Events, and Mortality in Kidney and Pancreas-Kidney Transplant Recipients.

BACKGROUND: Cardiovascular (CV) disease is the leading cause of death in kidney and simultaneous pancreas-kidney (SPK) transplant recipients. Assessing abdominal aortic calcification (AAC), using lateral spine x-rays and the Kaupilla 24-point AAC (0-24) score, may identify transplant recipients at higher CV risk. METHODS: Between the years 2000 and 2015, 413 kidney and 213 SPK first transplant recipients were scored for AAC at time of transplant and then followed for CV events (coronary heart, cerebrovascular, or peripheral vascular disease), graft-loss, and all-cause mortality. RESULTS: The mean age was 44 ± 12 years (SD) with 275 (44%) having AAC (26% moderate: 1-7 and 18% high: ≥8). After a median of 65 months (IQR 29-107 months), 46 recipients experienced CV events, 59 died, and 80 suffered graft loss. For each point increase in AAC, the unadjusted hazard ratios (HR) for CV events and mortality were 1.11 (95% CI 1.07-1.15) and 1.11 (1.08-1.15). These were similar after adjusting for age, gender, smoking, transplant type, dialysis vintage, and diabetes: aHR 1.07 (95% CI 1.02-1.12) and 1.09 (1.04-1.13). For recipients with high versus no AAC, the unadjusted and fully-adjusted HRs for CV events were 5.90 (2.90-12.02) and 3.51 (1.54-8.00), for deaths 5.39 (3.00-9.68) and 3.38 (1.71-6.70), and for graft loss 1.30 (0.75-2.28) and 1.94 (1.04-3.27) in age and smoking history-adjusted analyses. CONCLUSION: Kidney and SPK transplant recipients with high AAC have 3-fold higher CV and mortality risk and poorer graft outcomes than recipients without AAC. AAC scoring may be useful in assessing and targeted risk-lowering strategies.

Early allograft pancreatectomy-Technical failure or acute pancreatic rejection?

INTRODUCTION: "Technical failure" is still perceived to be a frequent cause of graft loss after pancreas transplantation. However, some early graft losses currently attributed to technical failure could be due to unrecognized acute pancreas rejection (APR). METHODS: We investigated the apparent incidence of APR in cases of early allograft pancreatectomy (EAP) that had previously been attributed to technical failure. We performed an analysis of 198 patients who underwent pancreas transplantation between January 2009 and January 2016 and identified all those with EAP within 90 days of transplantation. Explanted grafts of EAP recipients were re-examined histologically to evaluate for evidence of APR using current Banff criteria. RESULTS: Twenty-three EAPs were identified (11.6%; 23/198). APR was identified histologically in 9 out of the 15 recipients who lost their grafts due to duodenal leaks or recurrent peripancreatic collections, but was not identified in any of the patients whose grafts were lost due to thrombosis or ischemia. INTERPRETATION: Unsuspected APR appears common in the explanted grafts of recipients who have undergone EAP for apparently "technical" reasons. We suggest that EAP should be defined as a technical failure only when APR of the pancreas (or duodenum) has been excluded by histological analysis.

Changes in Gene Expression of Selected Genes in Patients with Type 1 Diabetes and Pancreas Transplant in Peripheral Blood.

BACKGROUND: Diabetes is an autoimmunologic disease that may have a different background. The aim of our study was to show that type 1 diabetes is accompanied by changes in gene expression in peripheral blood mononuclear cells. We analyzed the genes characteristic of pancreatic islet cells and genes playing a big part in autoimmune diseases and cancer. DESIGN: The study included 21 patients and was performed to examine the expression of 9 genes. The patients were divided into 3 research groups: people with type 1 diabetes, people with diabetes after pancreas transplant, and a control group of healthy patients. To assess the level of expression, RNA material was obtained from peripheral blood collected from individuals qualified for the study. RESULTS: The results of the study showed many interesting changes in the expression level of the analyzed genes. It was demonstrated that CASR gene expression was significantly higher in transplant patients than in diabetic patients. Differences in the level of activity are also noted in genes that take part in autoimmune diseases. PROPOSAL: Profiling gene expression in peripheral blood samples may be a useful and noninvasive diagnostic tool that allows early detection of changes leading to the onset or resumption of diabetes.

The incidence of fungal infections in pancreas transplant recipients in the absence of systemic antifungal prophylaxis.

BACKGROUND: There is a lack of high-level evidence identifying meaningful outcomes and the place in therapy for systemic perioperative antifungal prophylaxis (ppx) in pancreas transplant recipients. As our program does not routinely utilize systemic perioperative antifungal ppx in pancreas transplant recipients, we assessed the incidence of post-transplant infectious complications. METHODS: This was a single-center, retrospective cohort study of consecutive adult pancreas transplant recipients between 01/2016 and 04/2018 to describe the incidence of fungal infections. Patients with a history of previous simultaneous pancreas-kidney (SPK) transplant, HIV, or unexplained use of antifungal ppx after transplantation were excluded. The primary outcome was the incidence of fungal infections within 3 months after transplantation. RESULTS: After screening 60 patients, 56 met inclusion criteria. Within 3 months post-transplantation, two (3.6%) patients had a positive fungal culture requiring systemic antifungal treatment. The sources for infection in both cases were intra-abdominal fluid cultures, positive for Candida albicans. Both patients were treated with fluconazole. Allograft-related outcomes included a 6-month pancreas graft survival of 91.1% and pancreas transplant rejection incidence of 10.7%. CONCLUSION: In this single-center experience, pancreas transplant recipients not receiving systemic antifungal ppx had similar infectious and graft-related outcomes to what is reported in literature.