Murine cytomegalovirus promotes renal allograft inflammation via Th1/17 cells and IL-17A.

Human cytomegalovirus (HCMV) infection is associated with renal allograft failure. Allograft damage in animal models is accelerated by CMV-induced T helper 17 (Th17) cell infiltrates. However, the mechanisms whereby CMV promotes Th17 cell-mediated pathological organ inflammation are uncharacterized. Here we demonstrate that murine CMV (MCMV)-induced intragraft Th17 cells have a Th1/17 phenotype co-expressing IFN-γ and/or TNF-α, but only a minority of these cells are MCMV specific. Instead, MCMV promotes intragraft expression of CCL20 and CXCL10, which are associated with recruitment of CCR6+ CXCR3+ Th17 cells. MCMV also enhances Th17 cell infiltrates after ischemia-reperfusion injury, independent of allogeneic responses. Pharmacologic inhibition of the Th17 cell signature cytokine, IL-17A, ameliorates MCMV-associated allograft damage without increasing intragraft viral loads or reducing MCMV-specific Th1 cell infiltrates. Clinically, HCMV DNAemia is associated with higher serum IL-17A among renal transplant patients with acute rejection, linking HCMV reactivation with Th17 cell cytokine expression. In summary, CMV promotes allograft damage via cytokine-mediated Th1/17 cell recruitment, which may be pharmacologically targeted to mitigate graft injury while preserving antiviral T cell immunity.

Allo-specific immune response profiles indicative of acute rejection in kidney allografts using an in vitro lymphocyte culture-based model.

BACKGROUND: Ability to predict the manner in which a recipient's immune system would respond to a transplanted graft by analyzing cytokine profiles of the "allograft antigen sensitized" recipient lymphocytes in vitro might provide a means to identify patients at risk to adverse clinical endpoints. METHODS: Cytokine/chemokine gene expression profiles of peripheral blood mononuclear cells co-cultured with allograft antigen-pulsed macrophages were studied in 49 renal transplant recipients-12 with acute cellular rejection (ACR) with or without antibody-mediated rejection (AMR), 7 with AMR (without ACR), and 30 with stable allografts (SA). An 86-gene inflammatory cytokines and receptors PCR array was used to measure fold changes in gene expression between pulsed and un-pulsed cultures. RESULTS: On linear discriminant analysis and multivariate analysis of variance, a gene set comprising C3, CCL3, IL1B, TOLLIP, IL10, CXCL5, ABCF1, CCR3, IL10RB, CXCL1, and IL1R1 differentiated the ACR-AMR from the SA group. Similarly, a gene set comprising IL10, C3, IL37, IL1B, CCL3, CARD18, and TOLLIP differentiated the AMR from the SA group. No significant difference was found between the ACR-AMR vs AMR groups. CONCLUSION: Distinct post in vitro stimulation cytokine profiles at the time of transplantation thus correlated with the occurrence of post-transplantation rejection episodes which indicated feasibility of this in vitro model to assess the recipient's anti-graft response at an early stage.

Esophageal tuberculosis with coexisting opportunistic infections in a renal allograft transplant recipient.

We report a renal allograft transplant recipient with esophageal tuberculosis (TB) coinfected with herpes simplex virus (HSV) and Candida. The patient presented with oropharyngeal candidiasis and was started on fluconazole. Upper gastrointestinal endoscopy showed whitish patches with mucosal ulcers in the esophagus. Histopathological examination confirmed TB and HSV infection. The patient recovered after antiviral, antifungal, and anti-tubercular therapy with reduction in immunosuppression. In a TB-endemic zone, TB can coexist with opportunistic infections in an immunocompromised host.

Evaluation of oxidant and antioxidant status in living donor renal allograft transplant recipients.

The objective of this study was to evaluate the oxidant and antioxidant status in living donor renal allograft transplant recipients. Ninety-two renal transplant recipients with mean age of 34.75 ± 11.22 years were included in the present study. Venous samples of the recipients were drawn: before the transplant (baseline), 5 min after reperfusion, and 2 weeks after transplant. Samples were processed for the measurement of markers of oxidant and antioxidant status viz. malondialdehyde, catalase, glutathione peroxidase, reduced glutathione, ascorbic acid, and total antioxidant system. The mean baseline levels of reduced glutathione, ascorbic acid, and total antioxidant system were 1.61 ± 0.84 mg/g hemoglobin, 3.64 ± 1.49 mg/dL, and 1.42 ± 0.14 mmol/L which decreased at 5 min after reperfusion to 1.32 ± 0.72 (p = 0.010), 2.96 ± 1.25 (p = 0.002), and 1.36 ± 0.12 (p = 0.042), respectively. The malondialdehyde levels increased from a baseline value of 3.11 ± 1.02 µmol/mL to 3.32 ± 1.09 at 5 min after reperfusion (p = 0.344) and 4.01 ± 1.21 (p = 0.000) at 2 weeks. Glutathione peroxidase level decreased from 68.59 ± 32.79 units/g hemoglobin (baseline) to 63.65 ± 32.92 at 5 min after reperfusion (p = 0.530) and increased significantly at 2 weeks to 86.38 ± 37.18 (p = 0.00). There was no significant change in the catalase level. In living donor renal transplantation, oxidative stress starts after reperfusion and is reflected by fall in antioxidant factors and enzymes in the early period. Over the next 2 weeks, there is increased oxidative stress and simultaneous strengthening of antioxidant system which is implied by increase in malondialdehyde and improvement in the markers of antioxidant status.

Safety and efficacy of autologous mesenchymal stromal cells transplantation in patients undergoing living donor kidney transplantation: a pilot study.

AIM: This pilot study assesses the safety and feasibility of autologous mesenchymal stromal cell (MSC) transplantation in four patients that underwent living donor renal transplantation, and the effect on the immunophenotype and functionality of peripheral T lymphocytes following transplantation. METHODS: All patients received low dose ATG induction followed by calcineurin inhibitor-based triple drug maintenance immunosuppression. Autologous MSCs were administered intravenously pre transplant and day 30 post-transplant. Patients were followed up for 6 months. The frequency of regulatory T cells and T cell proliferation was assessed at different time points. RESULTS: None of the four patients developed any immediate or delayed adverse effects following MSC infusion. All had excellent graft function, and none developed graft dysfunction. Protocol biopsies at 1 and 3 months did not reveal any abnormality. Compared to baseline, there was an increase in the CD4 + CD25+FOXP3+ regulatory T cells and reduction in CD4 T cell proliferation. CONCLUSION: We conclude that autologous MSCs can be used safely in patients undergoing living donor renal transplantation, lead to expansion of regulatory T cells and decrease in T cell proliferation. Larger randomized trials studies are needed to confirm these findings and evaluate whether this will have any impact on immunosuppressive therapy.

Prevalence and genotypes of HPV in female renal transplant recipients in North India.

Estimation of the prevalence of high-risk human papillomavirus (HPV) genotypes in female renal transplant recipients is important for formulating strategies for prevention and screening of cervical cancer in the susceptible group. Data from developing countries are very limited. The study was prospective, cross-sectional, and hospital-based. Female renal transplant recipients, who had received the graft at least 6 mo earlier, were enrolled. Women who visited the outpatient unit for varied complaints and who underwent a normal cervical examination were recruited as controls. A pap smear was obtained in all women. HPV genotyping array kit was utilized for identifying 21 HPV genotypes. Forty renal transplant recipient women and 80 controls were enrolled. The median age of cases and controls was 40 yr (range, 24-69 yr) and 38 yr (range, 23-72 yr), respectively. The mean duration since transplant was 53±42.6 mo (range, 6-168 mo). There was no evidence of cervical dysplasia in any pap smear. High-risk HPV was detected in 32.5% (13/40) and 17.5% (14/80) of cases and controls, respectively (P=0.18). Of the 21 genotypes screened, 7 subtypes were detected. HPV 16 and 31 were the most common (5/13; 38.5%) subtypes observed in the cases, followed by HPV 18 (30.7%). HPV 16 was the most common subtype in controls (10/14; 71.4%). Five (38.5%) renal transplant recipients harbored multiple HPV genotypes, as compared with 4 (28.6%) controls (P=1.0). The prevalence of high-risk HPV in female renal transplant recipients was 1.9 times that observed among controls, although there was no evidence of cervical dysplasia.

An analysis of transplant glomerulopathy and thrombotic microangiopathy in kidney transplant biopsies.

Glomerular diseases of the transplanted kidney are the most important cause of poor long- term outcome. The estimation of the magnitude of this problem and an elucidation of pathogenic mechanism is essential for improvement of graft survival. This study from the Indian subcontinent aims (i) to determine the incidence of transplant glomerulopathy (TG) and thrombotic microangiopathy (TMA) in a large cohort of indicated renal transplant biopsies, (ii) to evaluate the histological and ultrastructural features of TG and TMA, and (iii) to assess the relationship between the two glomerular lesions. Of a total of 1792 indication renal transplant biopsies received over 5 years (2006-2010), 266 biopsies (of 249 patients) had significant glomerular pathology and were further analyzed along with immunofluorescence, electron microscopy (EM), and C4d immunohistochemistry. TG is the most common glomerular lesion followed by TMA seen in 5.97% and 5.08% of allograft biopsies, respectively, which constitutes 40.23% and 34.2% of biopsies with significant glomerular lesions. Pathologic antibody-mediated rejection (AMR) is associated with both TG and TMA in 71% and 46.5%, respectively. A coexistent TG was found in 18.4% of biopsies with TMA. Endothelial swelling with subendothelial widening, a feature of TMA, is also seen in early TG by EM. Our findings support the concept that TG evolves from a smoldering TMA of various causes.

Potential of organ donation from deceased donors: study from a public sector hospital in India.

Deceased donor organ programme is still in infancy in India. Assessing deceased donation potential and identifying barriers to its utilization are required to meet needs of patients with organ failure. Over a 6-month period, we identified and followed all presumed brainstem dead patients secondary to brain damage. All patients requiring mechanical ventilation with no signs of respiratory activity and dilated, fixed and nonreacting pupils were presumed to be brainstem dead. All events from suspicion of brainstem death (BSD) to declaration of BSD, approach for organ donation, recovery and transplants were recorded. Subjects were classified as possible, potential and effective donors, and barriers to donation were identified at each step. We identified 80 presumed brainstem dead patients over the study period. The mean age of this population was 35.9 years, and 67.5% were males. When formally asked for consent for organ donation (n = 49), 41 patients' relatives refused. The conversion rate was only 8.2%. The number of possible, potential and effective donors per million population per year were 127, 115.7 and 9.5, respectively. The poor conversion rate of 8.2% suggests a huge potential for improvement. Family refusal in majority of cases reflects poor knowledge and thus warrants interventions at community level.

Attitude and knowledge of healthcare workers in critical areas towards deceased organ donation in a public sector hospital in India.

BACKGROUND: The attitude of healthcare workers towards organ donation can either facilitate or hinder the process of organ donation. We assessed the attitude of healthcare workers employed in intensive or emergency care units of our hospital towards organ donation, and the influence of various factors on willingness for self-organ donation after death. METHODS: All doctors, paramedical workers, nursing staff and other staff members working in six distinct intensive or emergency care units in the hospital were requested to fill a completely anonymous, voluntary and self-administered questionnaire. Younger individuals, women and nurses constituted a majority of the study population. RESULTS: The questionnaire completion rate was 99%. About 55% of the study population were agreeable to donating organs after death and 27% were undecided. The factors that positively influenced their willingness to donate organs after death were favourable attitude of the spouse, religious beliefs supporting organ donation, knowledge of hospital's organ transplant programme, personal experience of the organ donation scenario, having ever donated blood or involvement in social activities, willingness to become an eye donor and willingness to become a living kidney donor. CONCLUSION: A largely favourable attitude towards organ donation was seen in our study population. However, the study reflects incomplete knowledge leading to confusion and thus, desire to know more among participants with respect to various aspects regarding organ donation. The factors identify that positively influence decisions regarding organ donation can be used as direct interventions.

Mesenchymal Stromal Cells Mediate Clinically Unpromising but Favourable Immune Responses in Kidney Transplant Patients.

BACKGROUND: Allograft rejection postkidney transplantation (KTx) is a major clinical challenge despite increased access to a healthcare system and improvement in immunosuppressive (IS) drugs. In recent years, mesenchymal stromal cells (MSCs) have aroused considerable interest in field of transplantation due to their immunomodulatory and regenerative properties. This study was aimed at investigating safety, feasibility, and immunological effects of autologous MSCs (auto-MSCs) and allogeneic MSCs (allo-MSCs) as a complement to IS drug therapy in KTx patients. METHODS: 10 patients undergoing KTx with a living-related donor were analysed along with 5 patients in the control group. Patients were given auto-MSCs or allo-MSCs at two time points, i.e., one day before transplant (D-0) and 30 days after transplant (D-30) at the rate of 1.0-1.5 × 106 MSCs per kg body weight in addition to immunosuppressants. Patients were followed up for 2 years, and 29 immunologically relevant lymphocyte subsets and 8 cytokines and important biomarkers were analysed at all time points. RESULTS: Patients displayed no signs of discomfort or dose-related toxicities in response to MSC infusion. Flow cytometric analysis revealed an increase in B regulatory lymphocyte populations and nonconventional T regulatory cells and a decrease in T effector lymphocyte proportions in auto-MSC-infused patients. No such favourable immune responses were observed in all MSC-infused patients. CONCLUSION: This study provides evidence that auto-MSCs are safe and well tolerated. This is the first ever report to compare autologous and allogeneic MSC infusion in KTx patients. Importantly, our data demonstrated that MSC-induced immune responses in patients did not completely correlate with clinical outcomes. Our findings add to the current perspective of using MSCs in KTx and explore possibilities through which donor/recipient chimerism can be achieved to induce immune tolerance in KTx patients.

Use of autogenous internal iliac artery for bridging the external iliac artery after excision of Aspergillus mycotic aneurysm in renal transplant recipients.

Repair of vascular defects in the presence of infection remains a challenging task in immunocompromised patients. We report two patients with postrenal transplant Aspergillus mycotic aneurysms of the allograft renal artery involving the external iliac artery which were excised along with the allograft. The defect in the external iliac artery was repaired successfully with interposition of autogenous internal iliac artery graft. Use of an internal iliac artery graft in such settings has been rarely reported in English literature. Autogenous internal iliac artery grafts provide a useful method to bridge the vascular defects created by radical debridement in the presence of fungal infections.

Challenges in containing the burden of hepatitis B infection in dialysis and transplant patients in India.

AIM: Whether or not completing the hepatitis B vaccination in patients who have undergone kidney transplantation in the middle of incomplete vaccination schedule leads to development of protective antibody titres is not known. This study was designed to determine whether the strategy of completing hepatitis B virus (HBV) vaccination after transplantation is efficacious. METHODS: Sixty-four end-stage renal disease (ESRD) patients were screened for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B surface antigen (anti-HBs), hepatitis B e-antigen (HBeAg) and HBV DNA. HBsAg negative patients received four doses of 40 µg recombinant HBV vaccine. Schedule was continued in after transplantation period if it was incomplete before transplant. Anti-Hbs titres were evaluated at 1, 3, 6, 9 and 12 months. RESULTS: Past HBV infection was noted in 12 patients: 10 by serology plus viraemia and two by viraemia alone. Of the 46 patients without current or past HBV infection who had received at least two doses of the vaccine before transplant, 17 each had received two and three doses and 12 had completed the schedule. Seventeen (37%) exhibited protective titres. Patients who had completed vaccination were more likely to have protective titres than those incompletely vaccinated (P = 0.02). Five patients responded to post-transplant vaccination. CONCLUSION: Partially vaccinated patients do not mount an adequate antibody response despite continued vaccination in the post-transplant period, whereas complete vaccination provides protection in 60%. The present study data highlights the need of administration of a full schedule of HBV vaccination before kidney transplantation. Nucleic acid-based tests can identify occult HBV infection.

Cytomegalovirus Infection in Postrenal Transplant Recipients: 18 Years' Experience From a Tertiary Referral Center.

BACKGROUND: Cytomegalovirus (CMV) reactivation or infection is one of the most important infectious complications in transplant recipient leading to significant morbidity and mortality. Its early detection and prompt treatment is imperative to improve transplant outcome. The present study estimated the frequency of CMV in renal transplant recipients (RTR). Various aspects of pp65Ag assay and quantitative real-time polymerase chain reaction (qRT-PCR) were evaluated in relation to the recent guidelines for CMV detection and treatment. METHODS: Retrospectively, data of clinically suspected cases of CMV (1610 out of total 2681 renal transplants) were analyzed along with a comparison of pp65Ag assay and qRT-PCR. RESULTS: The overall incidence of CMV syndrome was 14.25%; however, the incidence of CMV viremia in the clinically suspected group was 23.73%. The proportion of positive cases with pp65Ag assay and qRT-PCR were 13.6% (95% CI; 7.9-22.3) and 19.3% (95% CI; 12.4-28.8) with a substantial agreement (Cohen's kappa = 0.632) between the 2 techniques. CMV positive recipients were treated with ganciclovir until their viral count was negative or up to 3 weeks, followed by 3 months of prophylaxis with valganciclovir. No graft failure or mortality was reported secondary to CMV infection until 3 to 5 years of follow-up. RESULTS: CMV infection is quite prevalent in RTR, and early detection and immediate treatment or prophylaxis is of utmost importance. qRT-PCR is the gold standard and preferred over other methods; however pp65Ag assay still holds its importance in low-economic countries and populations where CMV infection is more prevalent and financial constraints are a major limitation.

Single-phase 16-slice multidetector computed tomographic angiography in the evaluation of the venous system in potential laparoscopic renal donors.

OBJECTIVE: Our objective was to assess the efficacy of single-arterial-phase, 16-slice multidetector computed tomographic (16-MDCT) angiography in the evaluation of both the renal arterial and venous systems in prospective renal donors with surgical (laparoscopic) correlation. METHODS: Fifty-one consecutive renal donors (age range, 20-62 years; 12 men and 39 women) underwent 16-MDCT angiography followed by laparoscopic donor nephrectomy. Approval from institutional review board was obtained with waiver of consent. The arterial-phase image data set was reviewed independently by 2 abdominal radiologists for the number of renal arteries and veins, anomalies, and degree of opacification of the renal veins. Computed tomographic angiography results were compared with the surgical findings. Interobserver agreement was assessed using kappa statistics. RESULTS: The sensitivity, specificity, and accuracy for identifying the number of renal veins in the arterial phase on 16-MDCT angiography were 96.3%, 96.07%, and 96.2% for reviewer 1 and 94.44%, 94.11%, and 94.3% for reviewer 2, respectively. Both reviewers correctly identified all venous anomalies and had substantial interobserver agreement (kappa coefficient = 0.68). CONCLUSIONS: A single-arterial-phase image data set is sufficient for evaluation of both the renal arterial and venous anatomy in potential renal donors before laparoscopic nephrectomy. Venous-phase acquisition is not necessary, thereby substantially reducing the radiation burden on the donor.

Successful Implantation of a Renal Allograft With Quintuple Arteries Retrieved From a Living Donor.

In renal transplant, multiple renal arteries in a donor require meticulous vascular reconstruction for successful allograft function in the recipient. Presence of more than 4 renal arteries is usually considered to be a relative contraindication for proceeding with renal donation. We report a living-donor renal transplant procedure where preoperative radiologic imaging of the donor showed 3 left renal arteries. Two additional arteries were identified intraoperatively. All 5 arteries were reconstructed during the back-table procedure, and the allograft was implanted in the recipient. At 3-month follow-up, computed tomographic imaging demonstrated patency of all 5 renal arteries, and the patient had a serum creatinine level of 0.8 mg/dL. Unidentified arteries on preoperative imaging may occasionally require complex reconstruction. A renal allograft with 5 renal arteries is usually a contraindication for renal donation. Here, we describe the first published case of successful kidney transplant after reconstruction of 5 renal arteries in the donor graft.

Effect of discontinuing morning dose of antihypertensive for renal transplant surgery on haemodynamic and early graft functioning: A prospective, double-blind, randomised study.

BACKGROUND AND AIMS: Antihypertensive drugs are continued until the day of renal transplant surgery. These are associated with increased incidence of hypotension and bradycardia. Hence, this study was designed to evaluate perioperative haemodynamic and early graft functioning in renal recipients with discontinuation of antihypertensive drugs on the morning of surgery. METHODS: This prospective, randomised, double-blind study recruited 120 patients. Group 1 patients received placebo tablet while Group 2 patients received usual antihypertensive drugs on the day of surgery. Perioperative haemodynamics and time for reinstitution of antihypertensives were the primary outcome measures. The secondary outcome measures were need for inotropic support and graft function. Perioperative haemodynamics were analysed using ANOVA and Student's t-tests with Bonferroni correction. Fischer's exact test was used for analysis. RESULTS: Systolic blood pressure (SBP) declined, which was more in Group 2. Forty-one patients developed significant hypotension; a correlation was found between the maximum observed hypotension and number of antihypertensive medications (P = 0.003). Four cases had slow graft function (one in Group 1 and three in Group 2). Twenty-eight patients in Group 2 required mephentermine boluses to maintain their SBP compared to 13 patients in Group 1 (P < 0.001). Two patients in Group 2 required dopamine to maintain SBP above 90 mmHg after the establishment of reperfusion as compared to none in Group 1. CONCLUSION: Single dose of long-acting antihypertensive drugs can be omitted on the morning of surgery without any haemodynamic fluctuations and graft function in controlled hypertensive end-stage renal disease renal transplant patients receiving a combined epidural and general anaesthesia.

Ultrasound-guided angioplasty for treatment of peripheral stenosis of arteriovenous fistula - a single-center experience.

PURPOSE: In patients with end-stage renal disease, arteriovenous fistulas (AVFs) are the access of choice for hemodialysis but are often complicated by stenosis. We present single-center experience of 78 ultrasound-guided angioplasty procedures for treating peripheral stenoses of AVFs. METHODS: Between January 2013 and November 2015, 78 angioplasties were performed under ultrasound guidance in 53 patients with end-stage renal disease who were referred from dialysis centers with low flow rate, difficult cannulation, increased cannulation site bleeding, immature or thrombosed AVF. Angioplasties were carried out in the presence of a structural lesion in the AVF resulting in at least 50% reduction in vein diameter with a blood flow of <250 mL/min or a peak systolic velocity >300 cm/s. Clinical success, anatomical success and post-intervention primary and secondary patency rates at 6, 12, 18 and 24 months were studied. RESULTS: In 49/53 patients (92.4%), 74 angioplasty procedures were successfully performed, whereas 4/53 patients (7.6%) had primary failure. A total of 35/49 patients (71.4%) underwent single angioplasty procedure whereas 14/49 patients (28.6%) underwent multiple angioplasty procedures. Post-intervention primary patency rates at 6, 12, 18 and 24 months were 78.6%, 60.2%, 53.8% and 48.9%, respectively. Post-intervention secondary patency rates at 6, 12, 18 and 24 months were 100%, 100%, 95.4% and 89%, respectively. Clinical success and anatomical success was 94.8% and 89.7%, respectively. CONCLUSIONS: Ultrasound-guided angioplasty is an effective method with good long-term outcomes in selected dialysis patients with peripheral stenosis of AVF.

Early recurrence of proliferative glomerulonephritis with monoclonal immunoglobulin deposits in a renal allograft.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMIDs) is a clinico-pathologic entity, the recurrence of which in the renal allograft has only recently been described. A 55-year-old male presented with rapid deterioration of renal function. Light microscopy showed membranoproliferative glomerulonephritis with kappa light chain restriction and only one sub-class of IgG. He subsequently underwent renal transplant. Two months later, he developed acute graft dysfunction. Renal biopsy showed a recurrence of the disease. Work up for multiple myeloma was positive. Membranoproliferative pattern of injury in the posttransplant setting has a wide range of differential diagnosis, PGNMID being one of them.

Management of Graft Duodenal Leak in Simultaneous Pancreas Kidney Transplant-a Case Report from India and Review of Literature.

Pancreatic transplantation is currently the only effective cure for Type 1 diabetes mellitus. It allows long-term glycemic control without exogenous insulin and amelioration of secondary diabetic complications. In India, pancreas transplant has not yet established with only a single successful transplant reported so far in the literature. We report a 24-year-old Type 1 diabetic patient with renal failure who underwent a simultaneous pancreas kidney transplant. On postoperative day 15, he had leak from the graft duodenal stump for which a tube duodenostomy and proximal diversion enterostomy was done. He had a high output pancreatic fistula following the procedure which was managed conservatively. The tube duodenostomy was removed at three and half months and enterostomy closure with restoration of bowel continuity was done at 6 months. After a follow up of 7 months, patient is doing well with a serum creatinine of 0.8 mg/dl and normal blood sugars, not requiring any exogenous insulin or oral hypoglycemic drugs. Managing patients with graft duodenal complications after pancreas transplant is challenging. Tube duodenostomy is a safe option in management of duodenal leak, although can lead to a persistent pancreatic fistula. A proximal diversion enterostomy allows early oral feeding and avoids the cost as well as the long term complications associated with parenteral nutrition.