Long-term (5 years) efficacy and safety of pancreas transplantation alone in type 1 diabetic patients.

BACKGROUND: Although combined pancreas and kidney transplantation is an established procedure for the treatment of type 1 diabetes (T1D) in patients with end-stage renal disease, the role of pancreas transplant alone (PTA) in the therapy of T1D subjects with preserved kidney function is still matter of debate. METHODS: We report our single-center experience of PTA in 71 consecutive T1D patients all with a posttransplant follow-up of 5 years. Patient and pancreas (normoglycemia in the absence of any antidiabetic therapy) survivals were determined, and several clinical parameters (including risk factors for cardiovascular diseases) were assessed. Cardiac evaluation and Doppler echocardiographic examination were also performed, and renal function and proteinuria were evaluated. RESULTS: Actual patient and pancreas survivals at 5 years were 98.6% and 73.2%, respectively. Relaparotomy was needed in 18.3% of cases. Restoration of endogenous insulin secretion was accompanied by sustained normalization of fasting plasma glucose concentrations and HbA1c levels as well as significant improvement of total cholesterol, low-density lipoprotein-cholesterol, and blood pressure. An improvement of left ventricular ejection fraction was also observed. Proteinuria (24 hours) decreased significantly after transplantation. One patient developed end-stage renal disease. In the 51 patients with sustained pancreas graft function, kidney function (serum creatinine and glomerular filtration rate) decreased over time with a slower decline in recipients with pretransplant glomerular filtration rate less than 90 mL/min. CONCLUSIONS: PTA was an effective and reasonably safe procedure in this single-center cohort of T1D patients.

Laparoscopic robot-assisted pancreas transplantation: first world experience.

BACKGROUND: Surgical complications are a major disincentive to pancreas transplantation, despite the undisputed benefits of restored insulin independence. The da Vinci surgical system, a computer-assisted electromechanical device, provides the unique opportunity to test whether laparoscopy can reduce the morbidity of pancreas transplantation. METHODS: Pancreas transplantation was performed by robot-assisted laparoscopy in three patients. The first patient received a pancreas after kidney transplant, the second a simultaneous pancreas kidney transplantation, and the third a pancreas transplant alone. Operations were carried out through an 11-mm optic port, two 8-mm operative ports, and a 7-cm midline incision. The latter was used to introduce the grafts, enable vascular cross-clamping, and create exocrine drainage into the jejunum. RESULTS: The two solitary pancreas transplants required an operating time of 3 and 5 hr, respectively; the simultaneous pancreas kidney transplantation took 8 hr. Mean warm ischemia time of the pancreas graft was 34 min. All pancreatic transplants functioned immediately, and all recipients became insulin independent. The kidney graft, revascularized after 35 min of warm ischemia, also functioned immediately. No patient had complications during or after surgery. At the longer follow-up of 10, 8, and 6 months, respectively, all recipients are alive with normal graft function. CONCLUSIONS: We have shown the feasibility of laparoscopic robot-assisted solitary pancreas and simultaneous pancreas and kidney transplantation. If the safety and feasibility of this procedure can be confirmed by larger series, laparoscopic robot-assisted pancreas transplantation could become a new option for diabetic patients needing beta-cell replacement.

Enteroscopic biopsies in the management of pancreas transplants: a proof of concept study for a novel monitoring tool.

BACKGROUND: Although percutaneous biopsies are considered to be the gold standard in diagnosing pancreas graft rejection, they are not performed routinely because of their association with severe complications. On the other hand, correct diagnosis of rejection is essential but may be difficult in cases of enteric drainage, particularly in patients with a pancreas transplant alone or a pancreas after kidney transplant. METHODS: Pancreas recipients who underwent enteroscopy between May 2005 and September 2009 were included in this retrospective analysis. Biopsies were graded 0 to 4 for interstitial and vascular changes. RESULTS: During the study period a total of 65 simultaneous pancreas-kidney transplants, 13 pancreas after kidney transplants and 4 pancreas transplants alone were performed. Sixty-three patients underwent a single enteroscopy, 10 had two, and 6 had three or more. Indications were protocol graft monitoring (n=73), graft dysfunction (n=17), enteric hemorrhage (n=9), or other (n=3). The duodenal segment was accessed in 76 instances (75%) with abnormal findings in 23. A total of 69 biopsies were obtained and revealed normal mucosa in 49 cases (71%). Histology showed signs of acute rejection in 11 cases. The upper gastrointestinal tract was also assessed, and, in 13 cases, additional pathologies were identified including gastroduodenitis (n=10), gastric/duodenal ulcer (n=2), and hemorrhagic esophagitis (n=1). No procedure-related complication occurred. CONCLUSIONS: This series of enteroscopies demonstrates that the duodenal segment of a pancreatic graft is accessible using our implant technique, and thus permitting biopsies to be obtained and endoscopic interventions to be performed.

Preservation of pancreas graft function after complete venous thrombosis: report of four cases treated conservatively.

BACKGROUND: Pancreas graft thrombosis is the most common cause of technical graft failure, with an incidence of up to 20% is some series. In most instances, vascular thrombosis of the graft will require immediate removal to avoid further abdominal complications. We present a total of four cases of complete venous thrombosis with preservation of function that were managed conservatively, resulting in long-term graft function. METHODS: Retrospective analysis of our case series over 10 years was carried out, obtaining patients with complete graft thrombosis by Doppler ultrasound. We included in the study only those patients who remained asymptomatic with preserved graft function. The clinical status of the patients, radiological findings, and therapeutic approach are evaluated. Patient and graft outcomes are analyzed. RESULTS: Retrospective evaluation of 227 transplants, a total of four patients were found to have complete thrombosis of the graft, remaining asymptomatic and preserving function without complications. Graft thrombosis was found on routine Doppler ultrasound evaluation of the transplanted organs at a median time of 19 days (range, 11-28 days), angiographic confirmation was obtained in all cases. The clinical condition and the presence of collateral flow allowed for conservative treatment. Median hospital stay was 29 days (range, 16-38 days), with a median follow-up of 106 months (range, 24-110 months), all patients are alive with a functioning graft. CONCLUSIONS: In rare instances with complete thrombosis of the pancreas transplant in absence of clinical manifestations, the grafts can be closely monitored and treated with systemic anticoagulation, allowing long-term patient and graft survival.

Intra-abdominal infections after simultaneous pancreas - kidney transplantation.

BACKGROUND: Intra-abdominal infections (IAI) are among the most common causes of pancreatic graft loss and recipient death in the early period after simultaneous pancreas - kidney transplantation (SPK). The aim of the study was to analyze risk factors and clinical consequences of IAI in SPK patients. MATERIAL/METHODS: Forty-six consecutive SPK performed from 2004 to 2010 were subjected to analysis. RESULTS: IAI developed in 10 recipients (21.7%). The group of recipients with IAI had a higher rate of patients that required transfusion of more than 2 blood units (90% vs. 47%, p=0.028) or relaparotomy (80% vs. 14%, p<0.001), in comparison with patients without IAI. Additionally, in patients with IAI, both delayed kidney graft function or primary kidney graft nonfunction (40% vs. 11%, p=0.001) and recipient death (40% vs. 3%, p=0.006) were more frequently observed. Logistic regression analysis revealed an increased risk of IAI development in patients who required early relaparotomy (OR=24.8, p<0.001), transfusion of more than 2 blood units (OR=12.6, p=0.02), or postoperative dialysis therapy (OR=14.1, p=0.003). CONCLUSIONS: Perioperative blood loss requiring transfusion and necessity of relaparotomy increase the risk of IAI after SPK. Development of IAI after SPK may result in impaired kidney graft function and increases patient mortality in the early postoperative period.

Donor-dependent risk factors for early surgical complications after simultaneous pancreas-kidney transplantation.

INTRODUCTION: The success of simultaneous pancreas-kidney transplantation (SPK) depends in a large degree on avoidance of surgical complications in the early postoperative period. The aim of the study was to analyze the Pre-procurement Pancreas Allocation Suitability Score (P-PASS) and the deceased donor parameters included within it as risk factors for early surgical complications after SPK. MATERIAL AND METHODS: Forty-six consecutive donors whose kidney and pancreas were simultaneously transplanted were included in the study. RESULTS: Donor age was older among recipients who lost their pancreatic grafts: 30.4±6.9 versus 24.1±6.9 years. Donor age was also older among recipients who lost their pancreatic grafts or died compared with those discharged with a functioning graft: 29.3±5.7 versus 24.0±6.9 years. Donor body mass index (BMI) was higher among patients who died compared with those who were discharged: 25.3±1.1 versus 23.2±2.5 kg/m2. P-PASS was higher in patients who lost their pancreatic grafts (17.6±2.1 vs 15.2±1.8) or died (15.3±1.9 vs 17.2±1.9), or lost pancreatic graft or died (15.2±1.8 vs 17.0±2.2) or with intra-abdominal infections (IAI; 17.1±1.7 vs 15.0±1.8). The incidence of donors≥30 years old was higher among recipients with IAI (45.4% vs 14.3%; P=.04). An higher rate of donors with P-PASS>16 was revealed among patients who lost their pancreatic grafts (26.7% vs 3.2%), died (26.7% vs 3.2%), lost the pancreatic graft or died (33.3% vs 6.4%), or experienced IAI (46.7% vs 9.7%). Multivariate logistic regression analysis revealed P-PASS (odds ratio 2.57; P=.014) and serum sodium (odds ration, 0.91; P=.048) to be important predictors of IAI development. CONCLUSION: Older age and higher BMI among deceased donors increased the risk of IAI, pancreatic graft loss, or recipient death after SPK. Transplantation of a pancreas from a donor with a low P-PASS score was associated with a lower risk of surgical complications after SPK.

Kidney-pancreas transplantation is associated with near-normal sexual function in uremic type 1 diabetic patients.

BACKGROUND: Sexual function is altered in patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD), thus affecting quality of life. The present study aimed to analyze sexual function in patients with T1D and ESRD (T1D+ESRD) who received a simultaneous kidney-pancreas (KP) or kidney-alone (KD) transplantation. METHODS: Ten KP, 10 KD, 9 T1D+ESRD patients and 11 healthy control subjects were evaluated according to the following parameters: (1) medical/sexual history and physical examination; (2) International Index of Erectile Function; (3) Beck's inventory for depression; (4) assessment of hormonal profile; (5) quantitative sensory testing of both hand and penile sensory thresholds; and (6) hemodynamic penile assessment. RESULTS: Controls and KP patients showed a higher rate of self-reported satisfactory erectile function as compared with KD and T1D+ESRD patients. Circulating androgens level resulted lower in both groups of transplanted patients and in patients with T1D+ESRD compared with healthy controls, albeit a relatively better profile was observed in KP. Both transplanted and T1D+ESRD patients showed peripheral hyposensitivity; however, healthy controls and KP showed better penile hemodynamic parameters compared with KD and T1D+ESRD. CONCLUSIONS: Our study demonstrates that sexual function, circulating sex steroids milieu, penile sensitivity, and hemodynamics are near-normalized for the most part in KP transplantation. Further studies are needed to assess the beneficial role and the overall impact of KP transplantation on sexual function in a long-term setting and a larger cohort of patients.

Impact of delayed pancreatic graft function in simultaneous pancreas-kidney transplantation.

OBJECTIVE: Simultaneous pancreas-kidney transplantation is an effective treatment for patients with type 1 diabetes mellitus and end-stage chronic kidney disease. Delayed pancreatic graft function is a common and multifactor condition with significant impact in short-term outcome of simultaneous pancreas-kidney transplantations. The aim of this study was to analyze the impact of pancreatic delayed pancreatic graft function on simultaneous pancreas-kidney transplantation. METHODS: Donor and recipient's demographic data, percentage of panel reactivity, acute rejection incidence, and patient and grafts survivals were retrospectively analyzed in 180 SPKT performed between 2002 and 2007. RESULTS: The incidence of pancreatic delayed pancreatic graft function was 11%. Donors older than 45 years had significant risk of pancreatic delayed pancreatic graft function (OR 2.26; p < 0,05). Patients with pancreatic delayed pancreatic graft function had higher rates of acute renal rejection (47 versus 24%; p < 0.05), altered fasting plasma glucose (25 versus 5%; p < 0.05) and mean glycated hemoglobin (5.8 versus 5.4%; p < 0.05), than patients without pancreatic delayed pancreatic graft function at the end of the first year of follow up. There were no significant differences between patients with and without pancreatic delayed pancreatic graft function regarding patient survival (95 versus 88.7%; p = 0.38), pancreatic graft survival (90 versus 85.6%; p = 0.59) and renal graft survival (90 versus 87.2%; p = 0.70), respectively at the sample period of time. CONCLUSION: Pancreatic delayed pancreatic graft function had no significant impact in the short-term outcome of simultaneous pancreas-kidney transplantations. Although delayed pancreatic graft function had no impact on 1-year pancreas graft survival, it contributed to early pancreas graft dysfunction, as assessed by enhanced insulin and oral anti-diabetic drugs requirements.

Donor pretreatment with tetrahydrobiopterin saves pancreatic isografts from ischemia reperfusion injury in a mouse model.

Depletion of the nitric oxide synthase cofactor tetrahydrobiopterin (H4B) during ischemia and reperfusion is associated with severe graft pancreatitis. Since clinically feasible approaches to prevent ischemia reperfusion injury (IRI) by H4B-substitution are missing we investigated its therapeutic potential in a murine pancreas transplantation model using different treatment regimens. Grafts were subjected to 16 h cold ischemia time (CIT) and different treatment regimens: no treatment, 160 µM H4B to perfusion solution, H4B 50 mg/kg prior to reperfusion and H4B 50 mg/kg before recovery of organs. Nontransplanted animals served as controls. Recipient survival and endocrine graft function were assessed. Graft microcirculation was analyzed 2 h after reperfusion by intravital fluorescence microscopy. Parenchymal damage was assessed by histology and nitrotyrosine immunohistochemistry, H4B tissue levels by high pressure liquid chromatography (HPLC). Compared to nontransplanted controls prolonged CIT resulted in significant microcirculatory deterioration. Different efficacy according to route and timing of administration could be observed. Only donor pretreatment with H4B resulted in almost completely abrogated IRI-related damage showing graft microcirculation comparable to nontransplanted controls and restored intragraft H4B levels, resulting in significant reduction of parenchymal damage (p < 0.002) and improved survival and endocrine function (p = 0.0002 each). H4B donor pretreatment abrogates ischemia-induced parenchymal damage and represents a promising strategy to prevent IRI following pancreas transplantation.

Outcomes after simultaneous pancreas and kidney transplantation and the discriminative ability of the C-peptide measurement pretransplant among type 1 and type 2 diabetes mellitus.

BACKGROUND: Earlier studies reporting outcomes after pancreas transplantation have included a combination of C-peptide cutoffs and clinical criteria to classify type 2 diabetes mellitus (T2DM). However, because the kidney is the major site for C-peptide catabolism, C-peptide is unreliable to discriminate the type of diabetes in patients with kidney disease. METHODS: To improve the discriminative power and better classify the type of diabetes, we used a composite definition to identify T2DM: presence of C-peptide, negative glutamic acid decarboxylase antibody, absence of diabetic ketoacidosis, and use of oral hypoglycemics. Additionally among T2DM patients with end-stage renal disease (ESRD), body mass index of <30 kg/m(2) and use of <1 u/kg of insulin per day were selection criteria for suitablity for simultaneous pancreas and kidney transplantation (SPKT). We compared graft and patient survival between T1DM and T2DM after SPKT. RESULTS: Our study cohort consisted of 80 patients, 10 of whom were assigned as T2DM based on our study criteria. Approximately 15% of patients with T1DM had detectable C-peptide. Cox regression survival analyses found no significant differences in allograft (pancreas and kidney) or patient survival between the 2 groups. The mean creatinine clearance at 1 year estimated by the modification of Diet in Renal Disease (MDRD) equation was not significantly different between the 2 groups. Among those with 1 year of follow-up, all patients with T2DM had glycosylate hemoglobin of <6.0 at 1 year versus 92% of those with T1DM. CONCLUSION: SPKT should be considered in the therapeutic armamentarium for renal replacement in selected patients with T2DM and ESRD. Use of C-peptide measurements for ESRD patients can be misleading as the sole criterion to determine the type of diabetes.

Pancreata from pediatric donors restore insulin independence in adult insulin-dependent diabetes mellitus recipients.

CONTEXT: The use of pediatric donors can increase the number of donors available for pancreas transplantation. AIM: The aim of this study was to verify if pancreas transplantation from pediatric donors is as effective as transplantation from adult donors to restore metabolic control in type 1 diabetic patients. MATERIALS AND METHODS: From 2000 to April 2009 we performed 17 pancreas transplantations from pediatric donors: 9 simultaneous kidney-pancreas (SPK), 6 pancreas transplantation alone (PTA), and 2 pancreas after kidney (PAK). All subjects received whole organs with enteric diversion of exocrine secretions; 11 underwent systemic and 6 underwent portal venous graft drainage. The immunosuppressive therapy was as follows: prednisone, mycophenolate mofetil, anti-thymocyte globulin (ATG), and cyclosporine or tacrolimus. The pediatric donor population had a mean age of 15.3 years (range, 12-17), a mean weight of 60.1 kg (range, 42-75), and a mean body mass index (BMI) of 21 (range, 17.9-23.4). RESULTS: After 9 years the overall patient survival rate was 94.12%, whereas the graft survival rate was 63.35%. Normal glucose and insulin levels were maintained either fasting or during oral glucose tolerance test (OGTT). The group of recipients of pediatric organs was compared with patients receiving organs from adult donors (n = 125); the mean glucose values were lower in the pediatric group, whereas insulin production was higher in the adult patients. Early venous thrombosis was 17.6% in the pediatric group and 20% in adult recipients (Fisher exact test, P = not significant [NS]). CONCLUSION: Pediatric donors restored insulin independence in adult diabetic recipients, representing a valid source of organs for pancreas transplantation.

Effects of pancreas transplantation on oxidative stress in pulmonary tissue from alloxan-induced diabetic rats.

PURPOSE: There is considerable evidence that cellular oxidative stress caused by hyperglycemia plays an important role in the genesis and evolution of chronic diabetic lesions. In this study, we determined the effectiveness of pancreas transplantation (PT) in preventing the imbalance caused by excessive production of reactive oxygen species over antioxidant defenses in lungs of rats rendered diabetic by alloxan injection. METHODS: Sixty inbred male Lewis rats, weighing 250-280 g, were randomly assigned to 3 experimental groups: NC, 20 nondiabetic control rats; DC, 20 untreated diabetic control rats; and PT, 20 diabetic rats that received syngeneic PT from normal donor Lewis rats. Each group was further divided into 2 subgroups of 10 rats each which were killed after 4 and 12 weeks of follow-up. Plasma glucose, glycosylated hemoglobin, and insulin levels were determined in all rats. Lipid hydroperoxide (LPO) concentrations and enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were measured in the pulmonary tissue of all rats. RESULTS: The DC rats showed elevated blood glucose and glycosylated hemoglobin levels, with insulin blood levels significantly lower than the NC rats (P < .001). They also showed significantly increased LPO concentrations in the lungs (P < .01) after 4 and 12 weeks of follow-up. In contrast, SOD, CAT, and GSH-Px antioxidant activities were significantly reduced in these periods (P < .01) 12 weeks after diabetes induction. Successful PT corrected all clinical and metabolic changes in the diabetic rats, with sustained normoglycemia throughout the study. Excessive lung LPO production and low SOD, CAT, and GSH-Px antioxidant activities were already back to normal 4 weeks after PT. CONCLUSION: PT can control oxidative stress in pulmonary tissue of diabetic rats. It may be the basis for preventing chronic diabetic lesions in lungs.

Pancreas transplantation prevents morphologic and ultrastructural changes in pulmonary parenchyma of alloxan-induced diabetic rats.

PURPOSE: The aim of this study was to evaluate whether pancreas transplantation (PT) is a suitable method for controlling histopathologic changes in lungs of alloxan-induced diabetic rats. METHODS: Sixty inbred male Lewis rats were randomly assigned to 3 experimental groups: NC, 20 nondiabetic control rats; DC, 20 untreated diabetic control rats; and PT, 20 diabetic rats that received syngeneic PT from normal donor Lewis rats. Each group was further divided into 2 subgroups of 10 rats each, which were killed after 4 and 12 weeks of follow-up. Clinical and laboratory parameters, fresh and fixed lung weights, and fixed lung volumes were recorded for all rats. Total number of alveoli, alveolar perimeter, alveolar surface area, and alveolar epithelial (AE) and endothelial capillary (EC) basal laminae thickening were randomly measured in 5 rats from each subgroup by using an image analyzer. For light microscopy, 250 alveoli were analyzed in each subgroup. For electron microscopy, 50 electron micrographs were examined for each subgroup. RESULTS: The DC rats showed elevated blood glucose and glycosylated hemoglobin levels, with insulin blood levels significantly lower than the NC rats (P < .001). Fresh and fixed lung weights and fixed volumes were significantly reduced in these rats, although their proportions to body weight were increased at 12 weeks (P < .01). The total number of alveoli in diabetic rats was higher than in control rats, whereas alveolar perimeter and surface area were significantly diminished (P < .01). AE and EC basal laminae were significantly thicker in DC than in NC (P < .01). Successful PT corrected all clinical and metabolic changes in diabetic rats, with sustained normoglycemia throughout the study. Morphologic and morphometric changes observed in diabetic lungs were completely prevented in PT rats from 4 weeks after transplant. CONCLUSION: We conclude that PT can control morphologic and ultrastructural changes in pulmonary parenchyma, suggesting a promising perspective for preventing other chronic diabetic lesions.

Islets of Langerhans are protected from inflammatory cell recruitment during reperfusion of rat pancreas grafts.

BACKGROUND: Ischemia/reperfusion (I/R) injury plays a pivotal role in the development of graft pancreatitis, with ischemia time representing one of its crucial factors. However, it is unclear, whether exocrine and endocrine tissue experience similar inflammatory responses during pancreas transplantation (PTx). This study evaluated inflammatory susceptibilities of islets of Langerhans (ILH) and exocrine tissue after different preservation periods during early reperfusion. METHODS: PTx was performed in rats following 2 h (2h-I) or 18 h (18h-I) preservation. Leukocyte-endothelial cell interactions (LEI) were analyzed in venules of acinar tissue and ILH in vivo over 2 h reperfusion. Nontransplanted animals served as controls. Tissue samples were analyzed by histomorphometry. RESULTS: In exocrine venules leukocyte rolling predominated in the 2h-I group. In the 18h-I group, additionally, high numbers of adherent leukocytes were found. Histology revealed significant edema formation and leukocyte extravasation in the 18h-I group. Notably, LEI in postcapillary venules of ILH were significantly lower. Leukocyte rolling was only moderately enhanced and few leukocytes were found adherent. Histology revealed minor leukocyte extravasation. CONCLUSION: Ischemia time contributes decisively to the extent of the I/R-injury in PTx. However, ILH have a significantly lower susceptibility towards I/R, even when inflammatory reactions in adjacent exocrine tissue are evident.

Influence of preexisting hepatitis C virus antibody positivity in simultaneous pancreas-kidney transplant recipients.

BACKGROUND: Preexisting hepatitis C virus (HCV) infection is implicated in diminished patient and graft survivals in renal transplant recipients. The impact of HCV infection on patient and graft survival in simultaneous pancreas-kidney transplantations is unclear. We evaluated the effect of preexisting HCV infection on patient and graft survival in simultaneous pancreas-kidney transplant (SPKT) recipients in the United States. METHODS: Using the Organ Procurement and Transplant Network/United Network for Organ Sharing database as of March 2009, adult primary SPKT recipients transplanted from 1995 to 2008 were studied. We stratified recipients based on pretransplant HCV status as HCV positive (HCV+) or HCV negative (HCV-). Overall kidney graft, pancreas graft, and patient survival were compared. RESULTS: A total of 10,809 adults received primary SPKT, of which 350 (3.2%) were HCV+. Less than 2% of the HCV+ recipients received organs from HCV+ donors. There were no significant differences in baseline donor and recipient characteristics between groups. Rates of acute kidney rejection at 1 year were similar: 22.9% for HCV+ and 23.0% for HCV- recipients (P=0.49). There was no difference in serum creatinine between groups up to 3 years. After controlling for confounding factors, HCV positivity was not associated with worsened overall kidney graft (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.61-1.03), pancreas graft (HR 0.80, 95% CI 0.63-1.00), or patient survival (HR 0.78, 95% CI 0.56-1.08). CONCLUSIONS: Only 3.2% of SPKT recipients had preexisting HCV infection. Preexisting HCV infection had no significant impact on kidney graft, pancreas graft, or patient survival.

Renal allograft failure predictors after PAK transplantation: results from the New England Collaborative Association of Pancreas Programs.

BACKGROUND: The reasons for kidney allograft failure subsequent to pancreas after kidney (PAK) are multifactorial; therefore, we examined these factors to identify a meaningful risk assessment that could assist in patient selection. METHODS: Five transplant centers in New England collaborated for this multiinstitutional retrospective study of 126 PAK transplantation recipients who had a functioning pancreas allograft 7 days after transplantation. Host factors (age at pancreas transplant, gender, body weight, glomerular filtration rate at 3 months pre-PAK and at 3-, 6-, 9-, and 12-month post-PAK, presence of proteinuria, pre- or post-PAK kidney rejection, pancreas rejection, cytomegalovirus disease, and HbA1C at 6-month post-PAK) and transplant factors (time to PAK, use of induction antibody therapy, and combinations of immunosuppressive medications) were assessed in both univariate and multivariate analyses for the primary outcome of kidney allograft failure. RESULTS: Of the variables assessed, factors associated with kidney allograft loss after PAK include impaired renal function in the 3 months before PAK, proteinuria, the occurrence of a post-PAK kidney rejection episode, and interval between kidney and pancreas transplantation more than 1 year. CONCLUSIONS: In our analysis, post-PAK kidney allograft loss was strongly associated with glomerular filtration rate less than 45 mL/min pre-PAK, K to P interval of over 1 year, pre-PAK kidney rejection episode, and pre-PAK proteinuria. Diabetic candidates for PAK with any of these conditions should be counseled regarding the risk of post-PAK renal transplant failure.

Family history of diabetes as a new determinant of insulin sensitivity and secretion in patients who have undergone a simultaneous pancreas-kidney transplant.

OBJECTIVES: We used homeostasis model assessment to investigate insulin sensitivity and secretion after a simultaneous pancreas-kidney transplant or kidney transplant alone. In that model, fasting plasma glucose and C-peptide levels are used to evaluate insulin sensitivity and beta-cell function. MATERIALS AND METHODS: Factors (eg, age, sex, race, delayed kidney allograft function) were correlated with homeostasis model assessment of beta-cell function and homeostasis model assessment of insulin sensitivity values after simultaneous pancreas-kidney transplant (n=89) or kidney transplant alone (n=68), and the results were compared with those in healthy subjects (n=49). RESULTS: Homeostasis model assessment of beta-cell function values were similar in patients who underwent kidney transplant alone or a simultaneous pancreas-kidney transplant, and were higher than homeostasis model assessment of beta cell function values in healthy subjects. The homeostasis model assessment of insulin sensitivity showed intermediate values for patients who underwent a simultaneous pancreas-kidney transplant and correlated with prednisone dosages (in those who underwent kidney transplant alone) and tacrolimus levels (in patients who underwent a simultaneous pancreas-kidney transplant). Homeostasis model assessment of beta-cell function values correlated with prednisone dosages in both groups and with tacrolimus levels in only those who underwent a simultaneous pancreas-kidney transplant. The body mass index of subjects who underwent kidney transplant alone correlated with both homeostasis model assessment of beta-cell function results and homeostasis model assessment of insulin sensitivity results. A family history of diabetes in subjects who underwent a simultaneous pancreas-kidney transplant correlated with homeostasis model assessment of beta-cell function results and homeostasis model assessment of insulin sensitivity results. CONCLUSIONS: Immunosuppressive regimen and body mass index were linked with reduced insulin sensitivity after kidney transplant. A family history of diabetes was linked with higher values of insulin secretion and lower insulin sensitivity in patients who underwent a simultaneous pancreas-kidney transplant.

An ex-vivo model for hypothermic pulsatile perfusion of porcine pancreata: hemodynamic and morphologic characteristics.

OBJECTIVES: Hypothermic machine perfusion is a well-established preservation method for kidneys that allows for better preservation over longer periods and pretransplant assessment of graft viability. This technique has only sporadically been used for pancreatic grafts. The aim of this study was to establish a hypothermic machine perfusion model for porcine pancreas perfusion. MATERIALS AND METHODS: Fifteen porcine pancreata were subjected to 25 minutes of warm ischemia and 149 minutes of cold ischemia before undergoing meticulous bench work preparation and perfusion, via an aortic segment, on the RM3 perfusion machine with University of Wisconsin (Barr Laboratories Inc., Pomona, NY, USA) solution. Perfusion variables (degrees C, temperature; mm Hg, systolic perfusion pressure; mL/min, flow volume; mm Hg/mL/min, resistance) were recorded every 30 minutes. Tissue samples were assessed for each pancreas preperfusion and postperfusion using a semiquantitative scoring scale to grade histopathologic changes: acinar cell damage (0-4), islet cell damage (0-3), inflammation (0-3), and edema (0-3). RESULTS: Hypothermic machine perfusion time was set at 315 minutes, and all grafts were maintained between 4-10 degrees C. The results were as follows (range, mean -/+ SD): systolic perfusion pressures were 5-13 mm Hg (9.61 -/+ 3.25 mm Hg) during the first 60 minutes (priming), and 15-23 mm Hg (21.07 -/+ 4.26 mm Hg) during the maintenance period. Target flow volumes reached 141-152 mL/min (147.6 -/+ 8.969 mL/min) at 60 pulses per minute. Intrapancreatic resistance decreased throughout priming to 0.03-0.09 mm Hg/mL/min (0.083 -/+ 0.042 mm Hg/mL/min), and remained unchanged until completion of perfusion. Pancreatic weight increase varied from 3.2% to 18.3% (13.36% -/+ 4.961%). There was significant postperfusion reduction in islet and acinar cell damage (P = .001 and P = .01 respectively). CONCLUSIONS: We have developed a model of machine perfusion for porcine pancreata which is simple, reliable, and protects graft histopathologic integrity. The model can be used in further studies to improve the quality of pancreas preservation, and assess and improve the viability of the condition of borderline pancreatic grafts.

Analysis of reoperations and their impact on the results of pancreas transplantation.

BACKGROUND: Many factors, including the advances in surgical techniques and immunosuppression, have been brought significant improvement to graft and patient survivals of patients undergoing pancreatic transplantations. However, one third of these patients require reoperations (ReOps). PURPOSE: We sought to evaluate the distribution of ReOps in the early or late postoperative period and analyze their impact on patient and graft survivals. PATIENTS AND METHODS: This unicenter, retrospective study was performed using data from 182 patient charts after pancreas transplantation from January 2000 through December 2007. RESULTS: We performed 88 ReOps on 73 patients; 43 early and 41 late operations. The simultaneous pancreas-kidney transplantation group showed a greater incidence of premature ReOps. The group undergoing early ReOp showed a lower survival rate (87.2%) compared with the nonoperated group, but a similar survival rate (97.5%) to the late ReOp group. In relation to the survival of pancreatic grafts after 1 year, the early ReOp group showed inferior survival to the late ReOp group, both of which were significantly worse results then those of the group without ReOp. CONCLUSION: ReOps were related to the success of the procedure. When they were performed in the first 3 months they had a negative impact on patient and graft survival.