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In kidney transplantation, de novo donor-specific antibodies (DSA) correlate with poor graft survival, and Consensus Guidelines recommend a protocol biopsy. In pancreas transplantation, DSA are also associated with poor graft outcomes; however, there are no recommendations on protocol biopsies. We started an antibody screening protocol on pancreas transplant patients at 0, 3, 6, 12 months, and yearly. Patients with DSA or high MFI non-DSA were considered for protocol biopsies of both organs. Results: 143 pancreas recipients were screened. 84 patients had negative antibodies throughout the study, 11 patients were found to have antibodies at graft dysfunction, and 48 patients had positive antibodies at screening without acute organ dysfunction (study group). Among the 30 non-DSA patients, 9 had protocol simultaneous pancreas and kidney biopsies performed with negative results in all of them. In contrast, among the 18 DSA patients, 15 had these biopsies performed, and 47% presented with subclinical rejection of the kidney, the pancreas, or both. In addition, some of the DSA patients without a protocol biopsy presented with rejection during the first 15 months of follow-up. Conclusion: We conclude that protocol biopsies of both grafts may play a role in the follow-up of pancreas transplant patients with de novo DSA appearance., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Simultaneous pancreas and kidney transplants offer significant therapeutic advantages but present a diagnostic approach dilemma in the diagnosis of rejection. Because both organs are from the same donor, the kidney has been treated traditionally as the "sentinel" organ to biopsy, presumably representing the status of both allografts. Truly concurrent biopsy studies, however, are needed to confirm this hypothesis. We examined 101 concurrent biopsies from 70 patients with dysfunction in either or both organs. Results showed concurrent rejection in 23 of 57 (40%) of cases with rejection; 19 of 57 (33.5%) and 15 of 57 (26.5%) showed kidney or pancreas only rejection, respectively. The degree and type of rejection differed in the majority (13 of 23, 56.5%) of cases with concurrent rejection, with the pancreas more often showing higher rejection grade. Taking into account pancreas dysfunction, a positive kidney biopsy should correctly predict pancreas rejection in 86% of the instances. However, the lack of complete concordance between the 2 organs, the discrepancies in grade and type of rejection, and the tendency for higher rejection grades in concurrent or pancreas only rejections, all support the rationale for pancreas biopsies. The latter provide additional data on the overall status of the organ, as well as information on nonrejection-related pathologies., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

As there is no precise laboratory test or imaging study for detection of pancreas allograft rejection, there is increasing interest in obtaining pancreas tissue for diagnosis. Pancreas allograft biopsies are most commonly performed percutaneously, transcystoscopically, or endoscopically, yet pancreas transplant surgeons often lack the skills to perform these types of biopsies. We have performed 160 laparoscopic pancreas biopsies in 95 patients. There were 146 simultaneous kidney-pancreas biopsies and 14 pancreas-only biopsies due to pancreas alone, kidney loss, or extraperitoneal kidney. Biopsies were performed for graft dysfunction (89) or per protocol (71). In 13 cases, an additional laparoscopic procedure was performed at the same operation. The pancreas diagnostic tissue yield was 91.2%; however, the pancreas could not be visualized in eight cases (5%) and in 6 cases the tissue sample was nondiagnostic (3.8%). The kidney tissue yield was 98.6%. There were four patients with intraoperative complications requiring laparotomy (2.5%) with two additional postoperative complications. Half of all these complications were kidney related. There were no episodes of pancreatic enzyme leak and there were no graft losses related to the procedure. We conclude that laparoscopic kidney and pancreas allograft biopsies can be safely performed with very high tissue yields., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Paracoccidioides brasiliensis is the cause of paracoccidioidomycosis, one of the most important systemic mycoses in Latin America. Human disease has been observed in a limited geographic and ecological niche, and it is attributed to exposure to the fungus in soil. Most primary infections are subclinical, as the infection is contained by the host mainly through cell-mediated immune response. However, as the fungus has the ability to survive in a dormant state for long periods, an impairment of the immune response may lead to reactivation and clinical disease. Surprisingly, paracoccidioidomycosis has rarely been reported in transplanted patients. The aim of this communication is to report a case occurring in a kidney recipient in an acute clinical form immediately after transplantation, and to review the available information on previously reported cases., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Multiple factors have been implicated in the process of ischemia-reperfusion injury (IRI) in organ transplantation. Among these factors, oxidative damage seems to initiate the injury. α-lipoic acid (ALA) is a potent antioxidant that is used in patients with diabetic polyneuropathy. The aim of the present study was to determine the effect of ALA in patients undergoing simultaneous kidney-pancreas transplant by evaluating the functional recovery of the graft and biochemical markers of IRI., Methods: Twenty-six patients were included in the following groups: (i) untreated control; (ii) donor and recipient (DR) ALA-treated, in which ALA was administered both to the deceased donor and to the recipients; and (iii) recipient ALA-treated group. The expression of inflammatory genes, as observed in biopsies taken at the end of surgery, as well as the serum cytokines, secretory leukocyte protease inhibitor, regenerating islet-derived protein 3β/pancreatitis-associated protein, amylase, lipase, glucose, and creatinine levels were quantified as markers of organ function., Results: The DR group showed high levels of TGFβ and low levels of C3 and TNFα in the kidneys, whereas high levels of C3 and heme oxygenase were identified in pancreas biopsies. Decreases in serum IL-8, IL-6, secretory leukocyte protease inhibitor, and regenerating islet-derived protein 3 β/pancreatitis-associated protein were observed after surgery in the DR group. Serum lipase and amylase were lower in the DR group than in the control and recipient groups. Early kidney dysfunction and clinical pancreatitis were higher in the control group than in either treatment group., Conclusions: These results show that ALA preconditioning is capable of reducing inflammatory markers while decreasing early kidney dysfunction and clinical posttransplant pancreatitis.

Simultaneous pancreas-kidney (SPK) transplantation is the treatment of choice for type 1 diabetics with end-stage renal disease. Recently patients with type 2 diabetes have been considered for transplantation. Despite that the patient and graft survival rates have improved over the past years, it continues to be a procedure with high surgical complication rates. We herein report a case of a pancreatic graft with a duodenal complication rescued using a total duodenectomy, a procedure that is seldom used. A 57-year-old type 2 diabetic underwent a SPK transplantation with systemic-enteric drainage. He was converted to a Roux en Y at day 7 for a small duodenal fistula without peritonitis. At day 13, with good graft function, he presented with gastrointestinal and abdominal bleeding. At laparotomy he had a congestive duodenum with intraluminal bleeding and an anastomotic fistula. We performed a total duodenectomy with enteric drainage. The patient was discharged home on day 39 with a pancreatic fistula on intramuscular Octretotide that lasted for 3 months. He was never readmitted and has good pancreas and kidney function at 16 months of follow-up. We think this is an option to rescue a pancreas graft with duodenal complications in selected cases.

Objective: Small donors have long been considered a potential source of organs for simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone (PTA). Our aim was to analyze our experience with SPK and PTA using small donors weighing <28 kg., Patients and Methods: Between September 2006 and October 2008, we performed 68 SPK, 3 PTA, and 3 pancreas after kidney transplantations (PAK). All recipients were adults with type 1 diabetes mellitus, including 8 who received small donor organs (<28 kg): 6 SPK and 2 PTA. We used 3 graft combinations for SPK: pancreas and single kidney; pancreas and en bloc kidneys; and en bloc dual kidney-pancreas. In contrast, we used conventional grafts for PTA. Mean weight among donors was 20.82 kg (range, 9.6-27 kg)., Results: We observed neither delayed graft function nor mortality. At a follow-up of approximately 281 days, all patients were free of insulin and dialysis treatments., Conclusions: Kidneys and pancreas from donors weighing <28 kg can be used in adult type 1 diabetic patients with excellent results. These small pediatric donors enabled us to enlarge the number of transplantations by 10.81%.

The increasing number of patients on waiting lists and the relatively stable organ procurement rate provide the groundwork for the use of expanded criteria deceased donors. While calcineurin-inhibitors (CNI) are excellent immunosuppressive drugs, their nephrotoxicity is largely responsible for the lack of improvement in long-term graft survival. The objective of this study was to analyze the results obtained with the use of a calcineurin inhibitor-free immunosuppressive protocol (polyclonal antibody induction, plus sirolimus, mycophenolate mofetil, and low doses of steroids) in terms of graft and patient survival as well as posttransplant clinical complications over 2 years. Under this immunosuppressive protocol, 78.04% of the patients completed the follow-up. A protocol biopsy was performed on 17 patients (53.1%) within 2 years posttransplant of which 82.31% were diagnosed as chronic allograph nephropathy grade I. The incidence of clinical complications was low and not significantly different from that reported with other immunosuppressive schemes. Death-censored graft survival was 95.12%. In conclusion, the use of a calcineurin inhibitor-free protocol in renal-transplant recipients of expanded criteria deceased donors was associated with excellent graft and patient survival rates and a low incidence of adverse events.

Objective: To analyze risk factors for Pneumocystis carinii pneumonia (PCP) in kidney transplant recipients., Study Design: In a case-control study, 17 PCP cases diagnosed between July 1994 and July 2000 were matched with two controls each (previous and subsequent kidney transplant recipients who did not develop PCP during the same follow-up period). Demographics, organ origin, human leukocyte antigen (HLA) mismatches, use of poly- or monoclonal anti-CD3 antibodies (Po/MoAb) for induction or rejection treatment, rejection episodes, cumulative steroid dose for rejection treatment, immunosuppressive regimens, and other infections were analyzed., Results: No significant differences were seen in gender (male 10 vs. 15), mean age (39.7 vs. 35.4 years), organ origin (cadaver donor 13 vs. 19), HLA mismatches, or Po/MoAb use in induction treatment. Significant differences were observed in PCP cases for rejection history (P=0.02), and median and total number of rejection episodes (P=0.0018). The relative risks for PCP for 1, 2, and > or =3 rejection treatments vs. no such treatment were 1, 1.05, and 6.30, respectively (P=0.021). The relative risk for PCP for steroid-resistant rejection was 4.34 (95% confidence interval [CI], 1.04-18.89) (P=0.019), and that for the use of Po/MoAb for rejection treatment was 7.23 (95% CI, 1.28-49.34) (P=0.006). The relative risk for PCP for 0, 1, and > or =2 previous or concomitant cytomegalovirus (CMV) infection vs. no such infections were 1.0, 2.32, and 13.0, respectively (P=0.012). The relative risks for PCP for tuberculosis (TB) was 18 (95% CI, 1.76-852.03), that for bacterial pneumonia was 14.22 (95% CI, 2.16-150.23), and that for hepatitis C virus infection was 5.25 (95% CI, 1.03-28.91). Immunosuppressive regimens with tacrolimus, mycophenolate mofetil (MMF), steroids (P=0.06), and MMF as a single variable (P=0.05) were more frequently used in cases. Primary trimethoprim-sulfamethoxazole prophylaxis failure was observed in 12 patients in association with heavy immunosuppression and concomitant infections., Conclusions: The risk of PCP in kidney transplant recipients is related to the number and type of rejection treatments. It is also related to the occurrence of CMV infection, and to other immunomodulating infections such as TB and hepatitis C, and might also be increased with the use of newer and more potent immunosuppressive agents. Primary prophylaxis failure may occur in association with some of these risk factors.

Background: The aim of this study was to compare the effectiveness of intravenous immunoglobulin (IVIg) versus monoclonal anti-CD3 as a treatment for steroid-resistant rejections. From January 1995 to June 1997, 30 patients were analyzed. They were randomized into two groups. Resistant rejections were diagnosed by core biopsy. Group A received 500 mg/ kg/day IVIg (Sandoglobulin) for 7 consecutive days, whereas group B received 5 mg/day of OKT3 for 14 consecutive days. Daily T cell CD3+ peripheral count was performed for 14 days for group B. The immunosuppression was similar for both groups. Cyclosporine was stopped during both treatments., Methods: Demographic factors, HLA mismatch, creatinine levels before and after treatment, and the incidence of rejections after treatment (up to 1 month) were taken into account for this study., Results: Data from different samples were compared using Fisher's exact test. Graft and patient survival were analyzed using the Kaplan-Meier method. The were no significant differences found in age, graft origin, HLA mismatch, or time of follow-up until the episode of rejection. Success was achieved for 11 (73.3%) of 15 of group A and 13 (86.6%) of 15 of group B (P=0.79). Creatinine levels before and after treatment were as follows: A, 2.99+/-1.30 mg/dl and 2.1+/-0.70 mg/dl versus B, 3.1+/-1.1 mg/dl and 2.5+/-0.8 mg/dl. Besides, we did not observe differences in the creatinine 1 month after treatment (A: 2.35+/-0.78 mg/dl; B: 2.51+/-1.10 mg/dl; P=0.66) nor in the third month (A: 1.83+/-0.58 mg/dl; B: 2.30+/-0.89 mg/dl; P=0.24). The incidence of rejections after treatment was 5 (46%) of 11 for group A and 9 (75%) of 12 for group B (P=0.4). The patient survival rates 2 years after treatment were 87 and 92% for A and B groups, respectively. Graft survival was identical (80% in both groups)., Conclusion: Should the favorable result presented in this report be confirmed in larger number of patients, IVIg could become the preferable choice of rejection treatment for steroid-resistant rejection because of a complete absence of the unwanted side effects commonly associated with OKT3.