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The role of induction in preemptive second kidney recipients is unclear. We examined the association between induction therapy and the long-term graft and recipient survival in the settings of tacrolimus and mycophenolate maintenance.We identified all preemptive second kidney transplant recipients between 2000 and 2020 in the Scientific Registry of Transplant Recipients. We excluded those with missing or mixed induction regimens and positive crossmatch. We grouped recipients by induction type into 3 groups: anti-thymocyte globulin (n = 1442), alemtuzumab (n = 362), and interleukin-2 receptor antagonist (IL-2RA; n = 481). We generated Kaplan-Meier curves of the recipient and death-censored graft survival (DCGS) with follow-up censored at 10 years. We used multivariable Cox proportional hazards models to examine the association between induction and the above outcomes. We adjusted the models for recipient and donor variables.Rates of delayed graft function, rejection, hospitalization, and post-transplant lymphoproliferative disorder at one year were not statistically different. Recipient survival did not vary by induction type in the Kaplan-Meier analysis (log-rank P = .189) or in the multivariable model. However, DCGS was the lowest in the Alemtuzumab group (log-rank P = .01). In the multivariable models, alemtuzumab was associated with a 57% increased risk of graft loss (1.57, 95% confidence interval (1.08, 2.30), P = .019) compared to anti-thymocyte. Live-donor kidneys were associated with significantly better recipient survival and DCGS.Compared to anti-thymocyte induction, alemtuzumab, but not IL-2RA, was associated with inferior graft survival in preemptive second transplant recipients discharged on tacrolimus and mycophenolate.

Steroid avoidance in kidney transplantation has been proven noninferior. Long-term outcome data on steroid avoidance in simultaneous pancreas-kidney (SPK) remains scant.Utilizing the Scientific Registry of Transplant Recipients between 2000 and 2020, we studied all primary crossmatch negative SPK recipients (N = 5683) who received antithymocyte globulin induction and were discharged alive with functioning grafts on tacrolimus and mycophenolate ± steroid maintenance. Recipients were grouped according to steroid use into 2 groups: steroid maintenance (n = 4191) and steroid avoidance (n = 1492). Kaplan-Meier curves censored at 10 y were generated for recipient and allograft survival by steroid maintenance. Predictors for recipient and graft survival were examined using Cox Proportional Hazards. Models were adjusted for age, body mass index, ethnicity, diabetes type, human leukocyte-antigen mismatches, cold ischemia time, transplant era, preemptive transplantation, and pancreas donor risk index with the transplant center included as a random effect.Steroid avoidance gained popularity over time, accounting for over one-fourth of the studied cohort. One-year acute rejection rates by steroid avoidance were comparable for kidney (8.6% versus 9%, P = 0.783); however, the pancreas rejection rate was lower in the steroid avoidance group (7.9% versus 10%; P = 0.035). After adjustment, steroid avoidance did not influence recipient survival (lower level of confidence interval, adjusted hazard ratio, upper level of confidence interval: 0.94, 1.15, 1.39), pancreas (0.75, 0.93, 1.16), or kidney (0.95, 1.18, 1.45) death-censored survival, compared with steroid maintenance.Accounting for the recipient and graft characteristics, steroid avoidance is associated with similar recipient, pancreas, and kidney graft outcomes compared with steroid maintenance in SPK recipients after antithymocyte globulin induction with tacrolimus and mycophenolate maintenance.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.

BACKGROUND Bariatric surgery (BS) may be associated with significant malabsorption and nutritional deficiencies. METHODS Between March 1987 and January 2017, we performed 922 liver transplants (LT) at our institution; 33 had antecedent BS. We matched the BS cohort to LT recipients without BS (1:3 matching) based on exact matching for gender and cancer and inverse variance matching for age, LT body mass index, MELD score, and transplant date. RESULTS We analyzed outcomes in 132 LT recipients (33 BS; 99 non-BS). The BS cohort comprised 26 (79%) women with a mean age of 52.4 years. The BS procedures included 20 Roux-en-Y gastric bypass (61%), 6 jejunoileal bypass (18%), 3 gastric band (9%), 2 sleeve gastrectomy (6%), and 1 duodenal switch (3%). The primary indications for LT listing were alcoholic cirrhosis (9; 27%), nonalcoholic steatohepatitis (7; 21%), hepatitis C (8; 24%), and hepatocellular carcinoma (3; 9%). At LT, body mass index for the BS cohort was 29.6, and MELD was 24. Compared with matched controls, BS recipients did not have longer LT length of hospital stay (17.8 versus 15.7 d, P = 0.71), longer intensive care unit length of stay (5.3 versus 4.1 d, P = 0.16), or higher 30-day complication rate (76% versus 85%, P = 0.43). Overall patient survival was similar (1- and 3-y survival was 90.1% and 75.9% for BS; 90.9% and 76.4% for non-BS, P = 0.34). CONCLUSIONS A history of BS does not portend a deleterious effect on LT outcomes.

Hydroxychloroquine is an antimalarial drug being tested as a potential treatment for the novel coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2. Although the efficacy of hydroxychloroquine for COVID-19 remains uncertain, it may serve as a potential prophylactic agent especially in those at high risk, such as healthcare workers, household contacts of infected patients, and the immunocompromised. Our aim was to identify possible hydroxychloroquine dosing regimens through simulation in those at high risk of infections by optimizing exposures above the in vitro generated half maximal effective concentration (EC50 ) and to help guide researchers in dose-selection for COVID-19 prophylactic studies. To maintain weekly troughs above EC50 in > 50% of subjects at steady-state in a pre-exposure prophylaxis setting, an 800 mg loading dose followed by 400 mg twice or 3 times weekly is required. In an exposure driven, post-exposure prophylaxis setting, 800 mg loading dose followed in 6 hours by 600 mg, then 600 mg daily for 4 more days achieved daily troughs above EC50 in > 50% subjects. These doses are higher than recommended for malaria chemoprophylaxis, and clinical trials are needed to establish safety and efficacy.

The superior death-censored graft survival of the pancreas allograft in simultaneous pancreas kidney transplants (SPK) over pancreas alone transplants (PTA) has long been recognized. Using data from the Scientific Registry of Transplant Recipients (SRTR) and a high-volume pancreas transplant program, we investigated the possible protective role of the kidney allograft in SPK transplants. We analyzed 19 043 primary pancreas transplants between 2000 and 2020, including 735 transplants performed at the University of Minnesota. SPK transplants demonstrated a superior death-censored graft survival over pancreas after kidney (PAK) and simultaneous pancreas and living donor kidney (SPLK) transplants, which both demonstrated better survival than PTA transplants. This effect was not affected by mode or duration of renal replacement therapy prior to transplant. Furthermore, we found that HLA match at the B-locus between the prior kidney and current pancreas allografts demonstrated a protective effect (HR .54; 95% confidence interval .29-1.00), with a 2-antigen match demonstrating superior death-censored graft survival to a 1- or 0-antigen match. We propose that a homologous kidney allograft in SPK transplants affords protection to the pancreas allograft-likely through a combination of better surveillance for rejection and direct immunoprotection offered by the same-donor kidney.

The overall number of pancreas transplants continued to increase to 1027 in 2018, after a nadir of 947 in 2015. New additions to waiting list remained stable, with 1485 candidates added in 2018. Proportions of patients with type II diabetes waiting for transplant (14.6%) and undergoing transplant (14.8%) have steadily increased since 2016. Waiting times for simultaneous pancreas/kidney transplant have decreased; median months to transplant was 13.5 for simultaneous pancreas/kidney transplant and 19.7 for pancreas transplant alone in 2018. Outcomes, including patient and kidney survival, as well as rejection rates, have improved consistently over the past several years. Pancreas graft survival data are being collected by the Organ Procurement and Transplantation Network and will be included in a future report once there are sufficient cohorts for analysis.

Background Living donor hepatectomy (LDH) is associated with significant postoperative hypophosphatemia. Methods From January 1997 through July 2017, we performed 176 LDH and compared donors who developed liver insufficiency (LI) to those that did not within 30 days of LDH. Using smoothing splines, we constructed a mixed-effects model and assessed receiver operating characteristic curves. Results Of the 176 donors, 161 were included in our study and 10 (6.2%) developed LI. The cohorts differed in minimum observed phosphate levels (1.77 mg/dL, LI cohort; 2.01 mg/dL No LI cohort) at a median nadir of 1.6 days (38 h) postoperatively (p = 0.003). In the ROC analysis, intraoperative time and postoperative phosphate levels best predicted LI (sensitivity, 90%; specificity, 55.6%). Conclusion Mean postoperative phosphate profiles differ significantly between those patients who develop LI and those who do not in the first 38 h after LDH.

Recent changes in policies guiding allocation of transplant kidneys are predicted to increase sharing between distant geographic regions. The potential exists for an increase in cold ischemia time (CIT) with resulting increases in delayed graft function (DGF) and transplant-related costs (TRC). We sought to explore the impact of CIT on metrics that may influence TRC.Between 2006 and 2014, 81 945 adult solitary deceased donor kidney transplants were performed in the United States; 477 (0.6%) at our institution. Regression models were constructed to describe the relationship between CIT on DGF and length of stay (LOS). Using hospital accounting data, we created regression models to evaluate the effect of DGF on LOS and TRC.In multivariable models, longer CIT was associated with an increased rate of DGF (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.38-1.44) and increased LOS (OR, 1.04; 95% CI, 1.02-1.05). Recipients at our institution who developed DGF had longer LOS (OR, 1.71; 95% CI, 1.50-1.95), suggesting that the effect is partially mediated by DGF. After adjusting for LOS, neither CIT nor DGF were independently associated with increased TRC. However, an increased LOS resulted in an increase in TRC by US $3422 (95% CI, US $3180 to US $3664) per additional day, indicating that the effect of CIT on TRC is partially mediated through LOS.The prolongation of CIT is associated with an increase in DGF rates and LOS, resulting in increased TRC. This study raises the need to balance increased access of traditionally underserved populations to kidney transplant with the inadvertent increase in TRC.

The Food and Drug Administration (FDA) has been regulating human islets for allotransplantation as a biologic drug in the US. Consequently, the requirement of a biological license application (BLA) approval before clinical use of islet transplantation as a standard of care procedure has stalled the development of the field for the last 20 years. Herein, we provide our commentary to the multiple FDA’s position papers and guidance for industry arguing that BLA requirement has been inappropriately applied to allogeneic islets, which was delivered to the FDA Cellular, Tissue and Gene Therapies Advisory Committee on 15 April 2021. We provided evidence that BLA requirement and drug related regulations are inadequate in reassuring islet product quality and potency as well as patient safety and clinical outcomes. As leaders in the field of transplantation and endocrinology under the “Islets for US Collaborative” designation, we examined the current regulatory status of islet transplantation in the US and identified several anticipated negative consequences of the BLA approval. In our commentary we also offer an alternative pathway for islet transplantation under the regulatory framework for organ transplantation, which would address deficiencies of in current system.

The combination of the transplant organ deficit, the increase in HCV nucleic acid positive donors (HCV NAT+), and the development of direct-acting antiviral agents (DAAs) has resulted in a rapid increase in HCV NAT+ organ transplants into HCV naive recipients. Early clinical experience with HCV NAT+ donor organs has shown promising outcomes; however, best practices are lacking to guide transplant programs during all phases of patient care. Transplant programs developing protocols for the utilization of HCV NAT+ organs will need a multidisciplinary team to address all aspects of pre-transplant and post-transplant patient care. Reports of fibrosing cholestatic hepatitis in HCV NAT+ organ transplant recipients receiving delayed DAA initiation highlight the need for the transplant community to develop safe and effective protocols. A failure to do so will inevitably lead to the erosion of public trust from cases of missed or inadequately treated donor-derived HCV infections. Herein, we provide best practice guidelines for the utilization of HCV NAT+ organs into HCV-negative recipients based on literature review and expert opinion from the faculty of the ASTS Standards and Quality Committee.

The overall number of pancreas transplants decreased slightly, from 1027 in 2018 to 1015, in 2019, up from a nadir of 947 in 2015. However, the number of simultaneous pancreas-kidney transplants (SPKs) increased in 2019, with a corresponding drop in pancreas-after-kidney transplants (PAKs) and pancreas transplants alone (PTAs). New waitlist registrations increased to 1772 in 2019, from 1606 in 2018. This was predominately driven by SPK listings, and those with type 2 diabetes. Waiting time for SPK decreased by 2 months, to a median of 12 months in 2019, but PTA recipient mean waiting time remained substantially higher, at 24 months, in 2018. Both short- and long-term outcomes, including patient survival, kidney graft survival, and acute rejection-free graft survival, have shown consistent improvement over the last decade. Pancreas graft survival data with the uniform definition of allograft failure is being collected by the Organ Procurement and Transplant Network (OPTN) and will be included in a future report.

Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368, Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888, Funder: Pisa University Hospital, Pisa, Italy, Funder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514, The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

An understanding of long-term outcomes for kidney transplant(KTx) recipients who survive with graft function beyond a specific time posttransplant is the first step in creating protocols to optimize care for current and improve outcomes for future recipients. We studied 831KTx recipients-580 living donor(LD); 251 deceased donor(DD)—with graft survival(GS) >20 years. For primary LD recipients, 25-year patient survival(PS) was 83%; 35-year, 59%. Their 25-year death-censored graft survival(DCGS) was 89%; 35-year, 72%. DD recipients had lower PS(P 3 antigens, pretransplant type 1 diabetes mellitus(DM1); in CNI era, a history of rejection, female gender. New comorbidities after 20 years were common: CVD(13%, non-DM1;18%, DM1), infections(27%, non-DM1;37%, DM1), 20-29 years posttransplant. Cancer after 20 years included: nonmelanotic skin cancer,22%; solid organ,7%; post-transplant lymphoproliferative disease(PTLD),2%. To improve long-term outcomes, clinical trials on prevention, recognition, and treatment of new comorbidities are needed.

Objective To identify factors that accurately predict 1-year survival for liver transplant recipients with a MELD score ≥40. Background Although transplant is beneficial for patients with the highest acuity (MELD ≥40), mortality in this group is high. Predicting which patients are likely to survive for >1 year would be medically and economically helpful. Methods The Scientific Registry of Transplant Recipients database was reviewed to identify adult liver transplant recipients from 2002 through 2016 with MELD score ≥40 at transplant. The relationships between 44 recipient and donor factors and 1-year patient survival were examined using random survival forests methods. Variable importance measures were used to identify the factors with the strongest influence on survival, and partial dependence plots were used to determine the dependence of survival on the target variable while adjusting for all other variables. Results We identified 5309 liver transplants that met our criteria. The overall 1-year survival of high-acuity patients improved from 69% in 2001 to 87% in 2016. The strongest predictors of death within 1 year of transplant were patient on mechanical ventilator before transplantation, prior liver transplant, older recipient age, older donor age, donation after cardiac death, and longer cold ischemia. Conclusions Liver transplant outcomes continue to improve even for patients with high medical acuity. Applying ensemble learning methods to recipient and donor factors available before transplant can predict survival probabilities for future transplant cases. This information can be used to facilitate donor/recipient matching and to improve informed consent.

Changes to the United States kidney allocation system targeted at reducing organ discard have failed to improve organ utilization. High Kidney Donor Profile Index kidneys continue to be discarded at high rates as a result of the regulatory and financial barriers to widespread utilization of these organs. However, there are potential changes to clinical practice that could improve organ utilization. Expediting the time from initial offer to final organ acceptance would reduce cold ischemic time and should improve utilization. Implementation of procurement biopsy standards to avoid biopsy of low risk organs may prevent organ discards due to inaccurate data or excessive cold ischemia time. Further, standardization of procurement biopsy pathological interpretation coupled with electronic accessibility would enable early acceptance of difficult to transplant organs. These changes to allocation practice patterns are vital given proposals to expand the geographic sharing of deceased donor kidneys. Implementation of new allocation policies must be evaluated to ensure they result in higher transplant rates and acceptable post-transplant outcomes.

Background. Complications associated with bladder-drained pancreata necessitating enteric conversion are common. Data on the outcomes after enteric conversion are conflicting. We studied the association between enteric conversion and the pancreas graft rejection, loss, and mortality. Methods. At our center, 1117 pancreas transplants were performed between 2000 and 2016. We analyzed 593 recipients with bladder-drained pancreata, of which 523 received solitary transplants and 70 received simultaneous pancreas-kidney transplants. Kaplan-Meier function was used to estimate time to conversion by transplant type. Cox proportional hazards models were utilized to evaluate patient survival, death-censored graft survival, and acute rejection-free survival while treating conversion as a time-dependent covariate. Subsequently, we examined the association between timing of conversion and the same outcomes in the conversion cohort. Results. At 10 y posttransplant, 48.8% of the solitary pancreas recipients and 44.3% of simultaneous pancreas-kidney transplant recipients had undergone enteric conversion. The enteric conversion was associated with 85% increased risk of acute rejection (hazard ratio [HR] = 1.85; 95% confidence interval [CI] = 1.37-2.49; P < 0.001). However, the conversion was not associated with graft loss or mortality. In the conversion cohort, a longer interval from engraftment to conversion was associated with an 18% lower rejection rate (HR = 0.82; 95% CI = 0.708-0.960; P = 0.013) and a 22% better graft survival (HR = 0.78; 95% CI = 0.646-0.946; P = 0.01). Conclusions. Enteric conversion was associated with increased risk of rejection, but not increased risks of graft loss or mortality. The decision to convert should consider the increased rejection risk. A longer interval from engraftment to conversion appears favorable.

Background An elevated body mass index (>30 kg/m2) has been a relative contraindication for living kidney donation; however, such donors have become more common. Given the association between obesity and development of diabetes, hypertension, and end-stage renal disease, there is concern about the long-term health of obese donors. Methods Donor and recipient demographics, intraoperative parameters, complications, and short- and long-term outcomes were compared between contemporaneous donors—obese donors (body mass index ≥30 kg/m2) versus nonobese donors (body mass index Results Between the years 1975 and 2014, we performed 3,752 donor nephrectomies; 656 (17.5%) were obese donors. On univariate analysis, obese donors were more likely to be older (P 30 days) readmissions. Estimated glomerular filtration rate and rates of end-stage renal disease were not significantly different between donor groups >20 years after donation (P = .71). However, long-term development of diabetes mellitus (adjusted hazard ratio (HR) 3.14; P Conclusion Obese donors develop diabetes mellitus and hypertension more frequently and earlier than nonobese donors after donation, raising concerns about increased rates of end-stage renal disease.

β-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas and Islet Transplant Association and European Pancreas and Islet Transplantation Association held a workshop to develop consensus for an International Pancreas and Islet Transplant Association and European Pancreas and Islet Transplant Association Statement on the definition of function and failure of current and future forms of β-cell replacement therapy. There was consensus that β-cell replacement therapy could be considered as a treatment for β-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA(1c)) and the occurrence of severe hypoglycemia. Optimal β-cell graft function is defined by near-normal glycemic control (HbA(1c) ≤6.5% [48 mmol/mol]) without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C-peptide. Good β-cell graft function requires HbA(1c) less than 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C-peptide production. Marginal β-cell graft function is defined by failure to achieve HbA(1c) less than 7.0% (53 mmol/mol), the occur-rence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C-peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed β-cell graft is defined by the absence of any evidence for clinically significant C-peptide production. Optimal and good function are considered successful clinical outcomes.

BACKGROUND Short- and intermediate-term results have been reported after rapid discontinuation of prednisone (RDP) in kidney transplant recipients. Yet there has been residual concern about late graft failure in the absence of maintenance prednisone. METHODS From October 1, 1999, through June 1, 2015, we performed a total of 1553 adult first and second kidney transplants-1021 with a living donor, 532 with a deceased donor-under our RDP protocol. We analyzed the 15-year actuarial overall patient survival (PS), graft survival (GS), death-censored GS (DCGS), and acute rejection-free survival (ARFS) rates for RDP compared with historical controls on maintenance prednisone. RESULTS For living donor recipients, the actuarial 15-year PS rates were similar between groups. But RDP was associated with increased GS (P = 0.02) and DCGS (P = 0.01). For deceased donor recipients, RDP was associated with significantly better PS (P < 0.01), GS (P < 0.01) and DCGS (P < 0.01). There was no difference between groups in the rate of acute or chronic rejection, or in the mean estimated glomerular filtration rate at 15 years. However, RDP-treated recipients had significantly lower rates of avascular necrosis, cytomegalovirus, cataracts, new-onset diabetes after transplant, and cardiac complications. Importantly, for recipients with GS longer than 5 years, there was no difference between groups in subsequent actuarial PS, GS, and DCGS. CONCLUSIONS In summary, at 15 years postkidney transplant, RDP did not lead to decreased in PS or GS, or an increase in graft dysfunction but as associated with reduced complication rates.

Introduction Kidney allograft torsion (KAT) is a rare complication of kidney transplantation (KT) that occurs when the transplanted kidney rotates around its vascular pedicle, which may result in a catastrophic compromise of the graft's blood supply, deterioration of kidney function, and eventually premature graft death. Case Report We report the case of a patient who had an acute kidney injury (AKI) episode from KAT. Her diagnosis was ascertained expeditiously and she had prompt surgical management. Five years after the KAT event, her baseline creatinine (Cr) stabilized around 1.6 mg/dL and she has achieved >8-year graft survival. Discussion This case illustrates the reversibility of injury that can occur after a KAT event with a commensurate return to baseline kidney function when KAT is promptly diagnosed and treated. A high index of suspicion of this uncommon but catastrophic complication of KT must be maintained to achieve desirable long-term outcomes. A diagnosis of KAT must be considered when routine etiologies of an acute deterioration of kidney allograft function have been excluded. Finally, prophylactic nephropexy must be strongly considered with intraperitoneal placement of a kidney allograft to avoid KAT.

Background Post-transplant malignancy (PTM) remains a concern among pediatric kidney transplant (PKT) recipients. Study Design Between 1963 and 2015, 884 pediatric (age 0 to 17 years old) patients received 1,055 PKTs at our institution. Cox proportional hazards models were constructed to identify risk factors for PTM after PKT with time-to-first-PTM as a primary outcome. Secondly, the hazard of death or graft loss was calculated in patients who developed PTM. Results Median patient survival was 33 years (interquartile range [IQR] 18.7 to 47 years); 260 patients died during the study period and 47 had been diagnosed with PTM. There were 235 PTMs that occurred in 136 (15.4%) recipients at a median age of 29 years (IQR 17.8 to 37 years). The percentages of patients with PTM were 13% at 20 years post-PKT and 26% at 30 years post-PKT. Of PTM patients who died, 63.8% died of PTM. Among those who developed PTM, there was a higher hazard of death or graft loss (hazard ratio [HR] 1.62; 95% CI 1.11 to 2.38). In multivariable proportional hazards models, factors associated with PTM were increasing age at PKT (adjusted HR [AHR] 3.14; 95% CI 1.80 to 5.48 for 14 to 17 year-olds compared with children less than 3 years), having a living unrelated donor (LURD; AHR 3.25; 95% CI 1.27 to 8.35 compared with a living related donor), or implanting an Epstein-Barr virus (EBV)-positive allograft in an EBV-negative recipient (AHR 5.66; 95% CI 1.11 to 29.0). Compared with the general population, the cancer rate for PKT recipients was 6 times higher (126 vs 21 per 100,000 person-years). Conclusions Pediatric kidney transplant recipients are at increased risk of PTM, which adversely affects survival. Children receiving transplants at an older age, from a LURD, or who receive an EBV-positive organ, should be monitored closely for the development of PTM.

The United Network for Organ Sharing recommends that fellowship-trained surgeons participate in 15 laparoscopic donor nephrectomy (LDN) procedures to be considered proficient. The American Society of Transplant Surgeons (ASTS) mandates 12 LDNs during an abdominal transplant surgery fellowship. We performed a retrospective intraoperative case analysis to create a risk-adjusted cumulative summation (RACUSUM) model to assess the learning curve of novice transplant surgery fellows (TSFs). Between January 2000 and December 2014, 30 novice TSFs participated in the organ procurement rotation of our ASTS-approved abdominal transplant surgery fellowship. Measures of surgical performance included intraoperative time, estimated blood loss, and incidence of intraoperative complications. The performance of senior TSFs was used to benchmark novice TSF performance. Scores were tabulated in a learning curve model, adjusting for case complexity and prior TSF case volume. Rates of adverse surgical events were significantly higher for novice TSFs than for senior TSFs. In univariable analysis, multiple renal arteries, high BMI, prior abdominal surgery, male donor, and nephrolithiasis were correlated with higher incidence of adverse surgical events. Based on the RACUSUM model, high intraoperative time is mitigated after 28 procedures, incidence of intraoperative complications tends to diminish after 24 procedures, and improvement in estimated blood loss did not remain consistent. TSFs exhibit a tipping point in LDN performance by 24-28 cases and proficiency by 35-38 cases.

In this study, our goal was to analyze nearly 4 decades of experience since the first living donor pancreas transplant in 1979, focusing on what constitutes optimal donor selection and ideal post donation follow-up. When combined with a living donor kidney transplant, a living donor pancreas transplant offers patients with concurrent renal failure and diabetes the option of a single procedure: a living donor simultaneous pancreas-kidney (SPK) transplant. Living donor SPK transplants not only can reduce the waiting time in areas where it is long but also, for highly sensitized patients, can electively identify a donor with a negative crossmatch. Although living donor pancreas (and simultaneous pancreas-kidney) transplants were initially performed open, they evolved to laparoscopic procedures in 1999. The technical failure rates have improved over the years. Guidelines for reducing donor morbidity have incorporated the use of biochemical markers and stricter donor selection criteria. Predonation assessment of donors’ beta-cell mass may help identify those at risk of developing diabetes. Living donor pancreas transplants can be performed safely and with good outcomes; they remain an important option for highly sensitized transplant candidates and can reduce waiting time in areas where it is long. For donors, stringent selection criteria, robust predonation counseling, and meticulous postdonation follow-up are essential.

Currently, two strategies exist for β-replacement therapy for type 1 diabetes mellitus: whole pancreas (PTx) and pancreas islet transplantation (ITx). PTx is by far the most common approach given the historic challenges of ITx at achieving insulin independence, the nuances of islet isolation techniques, and the attrition of functioning islets after transplant. One of the fundamental differences between PTx and ITx recipients lies in the indications for β-replacement. While end-stage renal disease from diabetic nephropathy is the primary indication for PTx, hypoglycemic unawareness remains the primary indication for ITx. Although the Edmonton protocol has made tremendous strides in the ITx field, enthusiasm has been tempered by long-term outcome data and its use of multiple deceased donors for a single recipient. Furthermore, of the donor risk characteristics that impact outcomes for PTx and ITx, donor age and obesity are the risk factors that have been most intensely studied and have shaped allocation policy. Currently, US allocation guidelines recommend that organs from older (> 50 years old) or obese (BMI > 30 kg/m2) donors should preferentially be allocated to ITx whereas younger and leaner donors are preferentially allocated to PTx. This has created discontent in the ITx community, viewing these allocation guidelines as unfair and unequal. To understand the evolution of deceased donor pancreas allocation, it is important to understand how specific donor risk factors, specifically age and obesity, have influenced the decision-making algorithm for choosing a specific modality over the other. Finally, it is critical to contextualize the historic allocation guidelines in the United States and the United Kingdom with considerations into how donor risk and payer reimbursement within each system have shaped this dynamic process.

In 2017, 1492 patients were added to the pancreas transplant waiting list, 964 listed as active, a slight increase from 2016. This is significant because for the first time in the past decade, the steady downward trend in additions to the waiting list has been reversed. Proportions of pancreas donors with cerebrovascular accident as cause of death decreased, with a concomitant increase in proportions with anoxia and head trauma. This is partly a result of the national opioid crisis, and it reflects increasing use of younger donors for pancreas transplant. The 2017 outcome report remains compromised by previous variation in reporting graft failure. Although the OPTN Pancreas Transplantation Committee has approved more precise definitions of pancreas graft failure, implementation of these definitions took place recently, and the data are not reflected in this report.

The number of pancreas transplants performed in the United States stabilized over the last 3 years after nearly a decade of steady decline. Numbers of new additions to the list also stabilized during the same period. Notably, the persistent decline in pancreas after kidney transplants also seems to have abated, at least for now. The first full year of data after implementation of the new pancreas allocation system revealed no change in the distribution of organs between simultaneous pancreas-kidney (SPK) transplant and pancreas transplant alone. The percentage of kidneys used in SPK transplants was also unchanged. While a uniform definition of pancreas graft failure was approved in June 2015, it is awaiting implementation. Meanwhile, SRTR will refrain from publishing pancreas graft failure data in the program-specific reports. Therefore, it is difficult to track trends in outcomes after pancreas transplant over the past 2 years. New initiatives by the OPTN/UNOS Pancreas Transplantation Committee include facilitated pancreas allocation and broadened allocation of pancreata across compatible ABO blood types to increase organ utilization.

To enhance selection of appropriate deceased donors for pancreas transplants, we sought to determine whether HLA matching improved posttransplantation outcomes. In this single-center study of 1219 pancreas transplants, we correlated posttransplantation outcomes with HLA-A, -B, -C, -DR, and -DQ matches and mismatches. Rejection was linearly correlated with the number of mismatches. The individual number of HLA mismatches reached significance at four or more with a 2.3- to 2.9-fold increase in rejection. The effect was most predominant with HLA-B (1.8-fold with one mismatch and 2.0-fold with two mismatches) and -DR (1.9-fold with two mismatches) loci, whereas HLA-A, -C, and -DQ matches or mismatches did not independently predict acute rejection. The affect was strongest in solitary pancreas transplants, with little impact for simultaneous pancreas and kidney (SPK). In contrast, HLA matching did not affect graft or patient survival rates but was associated with a reduced risk of opportunistic infection. Avoidance of acute rejection saved an estimated $32 000 for solitary pancreas recipients and $52 000 for SPK recipients in hospital costs. Our data do not support the use of HLA matching for predicting pancreas graft survival but do support its significance for the reduction of acute rejection, particularly for solitary pancreas recipients.

The development of minimally invasive surgical approaches to donor nephrectomy (DN) has been driven by the potential advantages for the donor, with questions remaining about long-term outcomes.All living DN performed from June 1963 through December 2014 at the University of Minnesota were reviewed. Outcomes were compared among 4 DN techniques.We performed 4286 DNs: 2759 open DN (ODNs), 1190 hand-assisted (HA) laparoscopic DNs (LDNs), 203 pure LDN (P-LDNs), and 97 robot-assisted-LDN. Laparoscopic DN was associated with an older (P0.001) and heavier (P0.001) donor population. Laparoscopic DN was associated with a higher probability of left kidney procurement (P0.001). All 3 LDN modalities required a longer operative time (P0.001); robot-assisted-LDN took significantly longer than HA-LDN or P-LDN. Laparoscopic DN decreased the need for intraoperative blood transfusion (P0.001) and reduced the incidence of intraoperative complications (P0.001) and hospital length of stay (P0.001). However, LDN led to a significantly higher rate of readmissions, both short-term (30 day, P0.001) and long-term (30 day, P0.001). Undergoing HA-LDN was associated with a higher rate of an incisional hernia compared with all other modalities (P0.001). For recipients, LDN seemed to be associated with lower rates of graft failure at 1 year compared with ODN (P = 0.002). The odds of delayed graft function increased for kidneys with multiple arteries procured via P-LDN compared with HA-LDN (OR 3 [1,10]) and ODN (OR 5 [2, 15]).In our experience, LDN was associated with decreased donor intraoperative complications and hospital length of stay but higher rates of readmission and long-term complications.

Background Living donor segmental pancreas transplants (LDSPTx) have been performed selectively to offer a preemptive transplant option for simultaneous pancreas-kidney recipients and to perform a single operation decreasing the cost of pancreas after kidney transplant. For solitary pancreas transplants, this option historically provided a better immunologic match. Although short-term donor outcomes have been documented, there are no long-term studies. Methods We studied postdonation outcomes in 46 segmental pancreas living donors. Surgical complications, risk factors (RF) for development of diabetes mellitus (DM) and quality of life were studied. A risk stratification model (RSM) for DM was created using predonation and postdonation RFs. Recipient outcomes were analyzed. Results Between January 1, 1994 and May 1, 2013, 46 LDSPTx were performed. Intraoperatively, 5 (11%) donors received transfusion. Overall, 9 (20%) donors underwent splenectomy. Postoperative complications included: 6 (13%) peripancreatic fluid collections and 2 (4%) pancreatitis episodes. Postdonation, DM requiring oral hypoglycemics was diagnosed in 7 (15%) donors and insulin-dependent DM in 5 (11%) donors. RSM with three predonation RFs (oral glucose tolerance test, basal insulin, fasting plasma glucose) and 1 postdonation RF, greater than 15% increase in body mass index from preoperative (Δ body mass index >15), predicted 12 (100%) donors that developed postdonation DM. Quality of life was not significantly affected by donation. Mean graft survival was 9.5 (±4.4) years from donors without and 9.6 (±5.4) years from donors with postdonation DM. Conclusions LDSPTx can be performed with good recipient outcomes. The donation is associated with donor morbidity including impaired glucose control. Donor morbidity can be minimized by using RSM and predonation counseling on life style modifications postdonation.

Biologic or biomechanical therapy capable of replacing the β cell mass has the potential to positively impact the health and well being of millions of people with insulindependent diabetes. Research in this area stands at a pivotal moment at which a number of viable strategies exist or are under development. Broad application depends on achieving both technical and financial feasibility. The ultimate goal of a "true cure," in which diabetic individuals achieve euglycemia with a single procedure associated with minimal risk, without long-termtoxic drugs, and unfettered by external devices and/or frequent monitoring, appears to still be some years away. However, dramatic progress has been achieved toward themore proximate objectives of improved glycemic control and elimination of hypoglycemia and long-term vascular complications. Long-term whole organ pancreas and isolated islet results have improved significantly over the last decade,with the latter now approaching the success of the former in insulin independence rates at the 5-year mark. It seems likely that allogeneic pancreas and islet transplantation will remain a treatment of choice for the foreseeable future in kidney recipients already obligated to lifelong immunosuppression until a more complete and permanent restoration of euglycemia is available. Nascent tolerance promoting protocols could aid in improving the risk-to-benefit balance for both islets and whole organ pancreas. With the present supply of transplantable pancreases used optimally, nomore than 13% of the annual incident cases of T1D can be cured. In practical terms though, today, fewer than 5% of the annual incident cases are transplanted. The reality of the limited supply of deceased donor organs ultimately constrains the impact of islet and pancreas transplantation and compels researchers to press forward to develop broader strategies such as the AP, xenogeneic islets, and stem cell-derived β cells for which the supply will be limitless; in these areas, recent progress has been most impressive. The AP continues to be refined withmore sophisticated delivery algorithms, improved sensors and exploration of mobile device control. For xenogeneic islets, dramatic progress is evident in the long-term survival of porcine islets in primates using genetically modified donors and/or improved biologic immunosuppressants. Microencapsulation and macroencapsulation devices that exclude direct immunity by physical means may further aid in fostering xenogeneic islet graft survival but will likely find their primary place in the containment and protection of early versions of stem cell-derived allogeneic β cells. Deriving functional β cells from stem cells has experienced the most celebrated recent advances. Improved differentiation protocols that permit large scale/ unlimited production of IPCs are nowavailable, and although "normal" β-cell function has not yet been achieved, the ever quickening pace of progress suggests they are not far off. Importantly, this therapeutic modality will ultimately need to confront the likely requirement for a containment device and the need to be retransplanted periodically. These blemishes notwithstanding, the tremendous perceived potential of the approach for clinical application is evident in the huge venture capital investment that was rapidly garnered after the report of the most recent advance in embryonic stem cell differentiation into proper β cells. Consistent with the informal survey we conducted, iPS-derived β cells, which currently suffer from regulatory hurdles and the lack of a viable business model, and the seemingly more remote regeneration of native β cells,may offer the ultimate chance for a personalized true cure of insulin-dependent diabetes by avoidance of barrier devices and toxic immunosuppressive drugs. The research agenda we have detailed is designed to facilitate full exploration of the potential of each proposed β-cell replacement solution so the optimal therapy is advanced as quickly as possible. Success in this endeavor will require broad and deep financial support from philanthropic (JDRF, Diabetes Research and Wellness Foundation, ADA, and so on) and public funding agencies worldwide; the investment needed is large but the potential reward will be profound. It is imperative that high impact, scientifically sound approaches are not overwhelmed by industry, private, or venture capital-supported priorities just because they hold a more lucrative near-term business model; scientific merit should dictate the course. The adherence of the historical funding agencies to traditional peer-reviewed methodology will be the incubator of novel approaches. This is a rapidly evolving landscape, and new data and novel ideas may radically divert the path forward. However, the diverse recent progress is tangible and undeniable, and the next decade is bound to witness a fascinating unfolding of competing solutions to cure insulin-dependent diabetes. Our assessment of the data presented creates the opportunity for IPITA/TTS to endorse the following broad agenda for specific support by the peer-reviewed agencies.

Kidney transplantation entails well-coordinated complex care delivery. Patient-provider cultural and linguistic discordance can lead to healthcare disparities. We analyzed kidney transplantation outcomes among our institution's Hmong recipients using a retrospective cohort study. From 1995 to 2015, 2164 adult (age ≥18) recipients underwent kidney transplantation at our institution; 78 self-identified as Hmong. Survival rates were analyzed and compared to Caucasian recipients (n = 2086). Fifty (64.1%) Hmong recipients consistently requested interpreters. Mean follow-up was 9.8 years for both groups. Hmong recipients (N = 78) were on average younger at transplant (45.7 vs 49.7 years; P = 0.02), more likely to be female (56% vs 38%; P = 0.001), and had higher gravidity (5.0 vs 1.9 births; P