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The National Kidney Registry (NKR) Advanced Donation Program enables living donors the opportunity to donate altruistically, or in advance of a potential recipient's transplant, and to receive a voucher that can be redeemed for a future transplant facilitated by the NKR. Family vouchers allow a donor to identify multiple individuals within their immediate family, with the first person in that group in need of a transplant being prioritized to receive a kidney. An increase in vouchers introduces concerns that demand for future voucher redemptions could exceed the supply of available donors and kidneys. A Monte Carlo simulation model was constructed to estimate the annual number of voucher redemptions relative to the number of kidneys available over a 50-year time horizon under several projected scenarios for growth of the program. In all simulated scenarios, the number of available kidneys exceeded voucher redemptions every year. While not able to account for all real-life scenarios, this simulation study found that the NKR should be able to satisfy the likely redemption of increasing numbers of vouchers under a range of possible scenarios over a 50-year time horizon. This modeling exercise suggests that a donor family's future needs can be satisfied through the voucher program.

This retrospective review of the largest United States kidney exchange reports characteristics, utilization, and recipient outcomes of kidneys with simple compared to complex anatomy and extrapolates reluctance to accept these kidneys. Of 3105 transplants performed, only 12.8% were right kidneys and 23.1% had multiple renal arteries. 59.3% of centers used fewer right kidneys than expected and 12.1% transplanted zero right kidneys or kidneys with more than 1 artery. Five centers transplanted a third of these kidneys (35.8% of right kidneys and 36.7% of kidneys with multiple renal arteries). 22.5% and 25.5% of centers currently will not entertain a match offer for a left or right kidney with more than one artery, respectively. There were no significant differences in all-cause graft failure or death-censored graft loss for kidneys with multiple arteries, and a very small increased risk of graft failure for right kidneys versus left of limited clinical relevance for most recipients. Kidneys with complex anatomy can be used with excellent outcomes at many centers. Variation in use (lack of demand) for these kidneys reduces the number of transplants, so systems to facilitate use could increase demand. We cannot know how many donors are turned away because perceived demand is limited.

Increasing numbers of compatible pairs are choosing to enter paired exchange programs, but motivations, outcomes, and system-level effects of participation are not well described. Using a linkage of the Scientific Registry of Transplant Recipients and National Kidney Registry, we compared outcomes of traditional (originally incompatible) recipients to originally compatible recipients using the Kaplan–Meier method. We identified 154 compatible pairs. Most pairs sought to improve HLA matching. Compared to the original donor, actual donors were younger (39 vs. 50 years, p < .001), less often female (52% vs. 68%, p < .01), higher BMI (27 vs. 25 kg/m(2), p = .03), less frequently blood type O (36% vs. 80%, p < .001), and had higher eGFR (99 vs. 94 ml/min/1.73 m(2), p = .02), with a better LKDPI (median 7 vs. 22, p < .001). We observed no differences in graft failure or mortality. Compatible pairs made 280 additional transplants possible, many in highly sensitized recipients with long wait times. Compatible pair recipients derived several benefits from paired exchange, including better donor quality. Living donor pairs should receive counseling regarding all options available, including kidney paired donation. As more compatible pairs choose to enter exchange programs, consideration should be given to optimizing compatible pair and hard-to-transplant recipient outcomes.

BACKGROUND: Despite the institution of a new Kidney Allocation System in 2014, A2/A2B to B transplantation has not increased as expected. The current Organ Procurement and Transplantation Network policy requires subtyping on two separate occasions, and in the setting of discrepant results, defaulting to the A1 subtype. However, there is significant inherent variability in the serologic assays used for blood group subtyping and genotyping is rarely done. METHODS: The National Kidney Registry, a kidney paired donation (KPD) program, performs serological typing on all A/AB donors, and in cases of non-A1/non-A1B donors, confirmatory genotyping is performed. RESULTS: Between 2/18/2018 and 9/15/2020, 13.0% (145) of 1,111 type A donors registered with the NKR were ultimately subtyped as A2 via genotyping. Notably, 49.6% (72) of these were subtyped as A1 at their donor center, and in accordance with OPTN policy, ineligible for allocation as A2. CONCLUSION: Inaccurate A2 subtyping represents a significant lost opportunity in transplantation, especially in KPD where A2 donors can not only facilitate living donor transplantation for O and highly sensitized candidates, but can also facilitate additional living donor transplants. This study highlights the need for improved accuracy of subtyping technique, and the need for policy changes encouraging optimal utilization of A2 donor kidneys.

Background and objectives In the United States, kidney paired donation networks have facilitated an increasing proportion of kidney transplants annually, but transplant outcome differences beyond 5 years between paired donation and other living donor kidney transplant recipients have not been well described. Design, setting, participants, & measurements Using registry-linked data, we compared National Kidney Registry (n=2363) recipients to control kidney transplant recipients (n=54,497) (February 2008 to December 2017). We estimated the risk of death-censored graft failure and mortality using inverse probability of treatment weighted Cox regression. The parsimonious model adjusted for recipient factors (age, sex, black, race, body mass index ≥30 kg/m2, diabetes, previous transplant, preemptive transplant, public insurance, hepatitis C, eGFR, antibody depleting induction therapy, year of transplant), donor factors (age, sex, Hispanic ethnicity, body mass index ≥30 kg/m2), and transplant factors (zero HLA mismatch). Results National Kidney Registry recipients were more likely to be women, black, older, on public insurance, have panel reactive antibodies >80%, spend longer on dialysis, and be previous transplant recipients. National Kidney Registry recipients were followed for a median 3.7 years (interquartile range, 2.1–5.6; maximum 10.9 years). National Kidney Registry recipients had similar graft failure (5% versus 6%; log-rank P=0.2) and mortality (9% versus 10%; log-rank P=0.4) incidence compared with controls during follow-up. After adjustment for donor, recipient, and transplant factors, there no detectable difference in graft failure (adjusted hazard ratio, 0.95; 95% confidence interval, 0.77 to 1.18; P=0.6) or mortality (adjusted hazard ratio, 0.86; 95% confidence interval, 0.70 to 1.07; P=0.2) between National Kidney Registry and control recipients. Conclusions Even after transplanting patients with greater risk factors for worse post-transplant outcomes, nationalized paired donation results in equivalent outcomes when compared with control living donor kidney transplant recipients.

Importance Although optimal access is accepted as the key to quality care, an accepted methodology to ascertain potential disparities in surgical access has not been defined. Objective To develop a systematic approach to detect surgical access disparities. Design, Setting, and Participants This cross-sectional study used publicly available data from the Health Cost and Utilization Project State Inpatient Database from 2016. Using the surgical rate observed in the 5 highest-ranked counties (HRCs), the expected surgical rate in the 5 lowest-ranked counties (LRCs) in North Carolina were calculated. Patients 18 years and older who underwent an inpatient general surgery procedure and patients who underwent emergency inpatient cholecystectomy, herniorrhaphy, or bariatric surgery in 2016 were included. Data were collected from January to December 2016, and data were analyzed from March to July 2020. Exposures Health outcome county rank as defined by the Robert Wood Johnson Foundation. Main Outcomes and Measures The primary outcome was the proportional surgical ratio (PSR), which was the disparity in surgical access defined as the observed number of surgical procedures in the 5 LRCs relative to the expected number of procedures using the 5 HRCs as the standardized reference population. Results In 2016, approximately 1.9 million adults lived in the 5 HRCs, while approximately 246 854 lived in the 5 LRCs. A total of 28 924 inpatient general surgical procedures were performed, with 4521 being performed in those living in the 5 LRCs and 24 403 in those living in the 5 HRCs. The rate of general surgery in the 5 HRCs was 13.09 procedures per 1000 population. Using the 5 HRCs as the reference, the PSR for the 5 LRCs was 1.40 (95% CI, 1.35-1.44). For emergent/urgent cholecystectomy, the PSR for the 5 LRCs was 2.26 (95% CI, 2.02-2.51), and the PSR for emergent/urgent herniorrhaphy was 1.83 (95% CI, 1.33-2.45). Age-adjusted rate of obesity (body mass index [calculated as weight in kilograms divided by height in meters squared] greater than 30), on average, was 36.6% (SD, 3.4) in the 5 LRCs vs 25.4% (SD, 4.6) in the 5 HRCs (P = .002). The rate of bariatric surgery in the 5 HRCs was 33.07 per 10 000 population with obesity. For the 5 LRCs, the PSR was 0.60 (95% CI, 0.51-0.69). Conclusions and Relevance The PSR is a systematic approach to define potential disparities in surgical access and should be useful for identifying, investigating, and monitoring interventions intended to mitigate disparities in surgical access that effects the health of vulnerable populations.

Timing of bilateral nephrectomy (BN) is controversial in patients with refractory symptoms of autosomal dominant polycystic kidney disease (APKD) in need of a renal transplant.Adults who underwent live donor renal transplant (LRT) + simultaneous BN (SBN) from August 2003 to 2013 at a single transplant center (n = 66) were retrospectively compared to a matched group of APKD patients who underwent LRT alone (n = 52). All patients received general health and polycystic kidney symptom surveys.Simultaneous BN increased operative duration, estimated blood loss, transfusions, intravenous fluid, and hospital length of stay. Most common indications for BN were pain, loss of abdominal domain, and early satiety. There were more intraoperative complications for LRT + SBN (6 vs 0, P = 0.03; 2 vascular, 2 splenic, and 1 liver injury; 1 reexploration to adjust graft positioning). There were no differences in Clavien-Dindo grade I or II (39% vs 25%, P = 0.12) or grade III or IV (7.5% vs 5.7%, P = 1.0) complications during the hospital course. There were no surgery-related mortalities. There were no differences in readmission rates (68% vs 48%, P = 0.19) or readmissions requiring procedures (25% vs. 20%, P = 0.51) over 12 months. One hundred percent of LRT + SBN allografts functioned at longer than 1 year for those available for follow-up. Survey response rate was 40% for LRT-alone and 56% for LRT + SBN. One hundred percent of LRT + SBN survey responders were satisfied with their choice of having BN done simultaneously.Excellent outcomes for graft survival, satisfaction, and morbidity suggest that the combined operative approach be preferred for patients with symptomatic APKD to avoid multiple procedures, dialysis, and costs of staged operations.

Kidney paired donation (KPD) is an important tool to facilitate living donor kidney transplantation (LDKT). Concerns remain over prolonged cold ischemia times (CIT) associated with shipping kidneys long distances through KPD. We examined the association between CIT and delayed graft function (DGF), allograft survival, and patient survival for 1267 shipped and 205 nonshipped/internal KPD LDKTs facilitated by the National Kidney Registry in the United States from 2008 to 2015, compared to 4800 unrelated, nonshipped, non-KPD LDKTs. Shipped KPD recipients had a median CIT of 9.3hours (range=0.25-23.9hours), compared to 1.0hour for internal KPD transplants and 0.93hours for non-KPD LDKTs. Each hour of CIT was associated with a 5% increased odds of DGF (adjusted odds ratio: 1.05, 95% confidence interval [CI], 1.02-1.09, P.9). This study of KPD-facilitated LDKTs found no evidence that long CIT is a concern for reduced graft or patient survival. Studies with longer follow-up are needed to refine our understanding of the safety of shipping donor kidneys through KPD.

The continued growth of kidney paired donation (KPD) to facilitate transplantation for otherwise incompatible or suboptimal living kidney donors and recipients has depended on a balance between the logistics required for patients and the collaborating transplant centers. The formation of chains for KPD and the shipping of kidneys have permitted networks such as the National Kidney Registry (NKR) to offer KPD to patients over a transcontinental area. However, over the last 3 years, we have encountered patient requests for a more flexible experience in KPD to meet their individual needs often due to rigid time constraints. To accommodate these requests, we have developed an Advanced Donation Program (ADP) in which the donor desires to donate by a specific date, but their paired recipient has not yet been matched to a specific donor or scheduled for surgery. After obtaining careful informed consent from both the donor and paired recipient, 10 KPD chains were constructed using an ADP donor. These 10 ADP donors have facilitated 47 transplants, and thus far eight of their paired recipients have received a kidney within a mean of 178 (range 10-562) days. The ADP is a viable method to support time limited donors in a KPD network.

The development of cytomegalovirus (CMV) drug resistance has become an emerging clinical challenge. In kidney transplant recipients (KTR), CMV infection is a risk factor for acute rejection, has a detrimental effect on patient survival, and predisposes patients to secondary opportunistic infections. We report here the case of a kidney transplant patient on valganciclovir prophylaxis who developed recurrent CMV infections, complicated by UL97 ganciclovir (GCV) resistance. Our patient underwent unsuccessful treatment courses with high dose GCV, foscarnet and cidofovir. Compassionate use maribavir was initiated and resulted in full recovery. Through this case report and literature review, we highlight potential strategies for the successful management of CMV resistance.

The single-port approach has been associated with an unacceptably high rate of umbilical port hernias in large series of patients undergoing single-port cholecystectomy and colectomy and with additional surgical risks thought secondary to technical and ergonomic limitations. A retrospective review of 378 consecutive laparoendoscopic single-site(LESS) donor nephrectomies performed between 04/15/2009 and 04/09/2014 was conducted. Twelve patients (3%) developed an umbilical hernia. Eleven (92%) were female and eight (73%) of these patients had a prior pregnancy. Hernias were reported 13.5 ± 6.9 months after donation, and the mean size was 5.1 ± 3.7 cm. Seven additional cases (1.9%) required a return to the operating room for internal hernia (2), evisceration (1), bleeding (1), enterotomy (1), and wound infection (2). The original incision was utilized for reexploration. One patient required emergent conversion to an open procedure for bleeding during the initial donation. There were no mortalities. Recipient patient and graft survival were 99% and 99% at 1 year, respectively. Although reports associated with earlier experiences with single-site procedures suggested an unacceptably high rate of hernias at the surgical site, this does not seem to be the case at our center. This technique is a reliable surgical technique for left donor nephrectomy at this institution.

The characteristic of our diabetic population has been ever changing. No longer are our Type 1 diabetics young and thin; they too suffer from the obesity epidemic and now present later with the complications of diabetes (renal dysfunction, hypoglycemic unawareness, vision loss, neuropathy, etc.). Even with all of our medical and technological advances to combat diabetes, there are many who are not very well controlled. We evaluated the pancreas transplant recipients in the last three years at the University of Maryland to study the outcomes of these older and higher body mass index (BMI) recipients, as well as the impact of using older and higher BMI donors. We saw no difference in the survival of the patient or the allograft of recipients who were older or had higher BMIs. We also saw no difference in morbidity for these patients. There also was no difference when using older or higher BMI donor organs, longer cold ischemic times, different types of donors (donation after cardiac death versus brain dead donors), or different types of organs (simultaneous pancreas kidney, pancreas transplant alone, or pancreas after kidney). In reviewing our waitlist, our patients range widely in age and BMI. As long as they are fit for surgery, we will continue to transplant our ever growing population of older and obese diabetics without any more adverse outcomes than occur in our normal weight and younger patients.

Purpose To explore the safety and efficacy of PRT-201. Methods Randomized, double-blind, placebo-controlled, single-dose escalation study of PRT-201 (0.0033 to 9 mg) applied after arteriovenous fistula (AVF) creation. Participants were followed for one year. The primary outcome measure was safety. Efficacy measures were the proportion with intra-operative increases in AVF outflow vein diameter or blood flow ≥25% (primary), changes in outflow vein diameter and blood flow, AVF maturation and lumen stenosis by ultrasound criteria and AVF patency. Results The adverse events in the PRT-201 group (n=45) were similar to those in the placebo group (n=21). There were no differences in the proportion with ≥25% increase in vein diameter or blood flow, successful maturation or lumen stenosis. There was no statistically significant difference in primary patency between the dose groups (placebo n=21, Low Dose n=16, Medium Dose n=17 and High Dose n=12). In a subgroup analysis that excluded three participants with early surgical failures, the hazard ratio (HR) for primary patency loss of Low Dose compared with placebo was 0.38 (95% CI 0.10-1.41, P=0.15). In a Cox model, Low Dose (HR 0.27, 95% CI 0.04-0.79, P=0.09), white race (HR 0.17, 95% CI 0.03-0.79, P=0.02), and age Conclusions PRT-201 was not different from placebo for safety or efficacy measures. There was a suggestion for improved AVF primary patency with Low Dose PRT-201 that is now being studied in a larger clinical trial.

BACKGROUND Candidacy for kidney transplantation is being progressively liberalized, and the safety and efficacy of early withdrawal of corticosteroids in high-risk patients have not been fully characterized. METHODS We analyzed the safety and efficacy of an early corticosteroid withdrawal regimen of rabbit antithymocyte globulin induction, tacrolimus, mycophenolate mofetil, and steroid withdrawal by day 5 after transplantation in our study cohort of 634 kidney transplant recipients that included 27% African American and 18% Hispanic recipients. Fifty-five percent of the recipients were recipients of deceased-donor kidneys, and 46% of deceased-donor kidneys were kidneys from expanded criteria donors. RESULTS Kaplan-Meier patient survival at 1, 3, and 5 years after transplantation was 98.6%, 94.6%, and 90.2%, and death-censored graft survival was 96.2%, 91.9%, and 87.6%, respectively. During a mean follow-up of 57 months, 89.3% of patients remained off of corticosteroids, and the incidence of acute rejection including subclinical rejection identified by protocol biopsy was 12.0%. Multivariable analysis identified age older than 60 years as protective against (P=0.01) and the African American ethnicity as a risk factor for (P=0.03) rejection. Delayed graft function (P

BACKGROUND Despite the increasing use of older living donors in kidney transplantation, intermediate-term donor and recipient outcomes are poorly characterized. METHODS We retrospectively compared 143 recipients from donors older than 50 years (older) to 319 recipients from donors 50 years or younger (younger). RESULTS Mean older donor age (years) was 58; younger age was 37 (P

Laparoendoscopic single-site (LESS) surgery has been shown to be feasible in living donor nephrectomies (DNs). Obesity is an established risk factor for perioperative morbidity. We sought to determine whether LESS-DN is safe and effective in the obese (body mass index [BMI] ≥30 kg/m(2)) population.Between August 2009 and September 2010, 125 consecutive LESS-DN were performed; 32 patients were obese. This group was matched to 32 nonobese LESS-DN (BMI30 kg/m(2)) patients, 32 obese conventional laparoscopic DN (obese LAP-DN) patients, and 32 nonobese LAP-DN patients. Comparison parameters included organ recovery time, operative time, estimated blood loss (EBL), warm ischemia time (WIT), incision length, complications, and recipient allograft function.Demographic data were similar between the groups, except BMI (P0.0001). Organ recovery time, EBL, WIT, complications, and recipient allograft function were similar between the obese LESS-DN group and the other three groups (P0.05). Total operative time was longer in the obese LESS-DN compared with the nonobese LAP-DN (P0.0001); however, incision length was shorter in the obese LESS-DN group compared with either LAP group (P0.0001). Complete LESS-DN was successful in 62 (97%) cases (two obese donor cases were converted to hand-assisted laparoscopy).Our results indicate that LESS-DN can be performed safely in obese donors without increased donor morbidity and similar recipient allograft outcomes compared with ideal-sized donors as well as with conventional LAP-DN patients.

Afaneh C, Rich B, Aull MJ, Hartono C, Kapur S, Leeser DB. Pancreas transplantation considering the spectrum of body mass indices. Clin Transplant 2011: 25: E520–E529. © 2011 John Wiley & Sons A/S. Abstract: Background: In kidney, liver, heart, and lung transplantation, extremes of body mass index (BMI) have been reported to influence post-operative outcomes and even survival. Given the limited data in pancreas transplantation, we sought to elucidate the influence of BMI on outcomes. Methods: We reviewed 139 consecutive pancreas transplants performed at our institution and divided them into four categories based on BMI: underweight (≤18.5 kg/m2), normal (18.6–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2). Parameters analyzed included post-operative complications, early graft loss, one-yr acute rejection rate (AR), non-surgical infections, and survival. Results: Demographic data were similar between the groups. Compared with normal, only obese patients trended toward more post-operative complications (p = 0.06). Underweight and obese patients had significantly more post-operative infectious complications than normal (p = 0.0005 and p = 0.03, respectively). Obese patients had more complications requiring percutaneous drainage compared with normal (p = 0.03). Overweight and obese patients had significantly more complications requiring re-laparotomy (p = 0.03 and p = 0.048, respectively). Early graft loss, AR, non-surgical infections, and patient and graft survival rates were not different between normal and underweight, overweight, or obese patients (p > 0.05). Conclusions: Extremes of BMI were associated with increased morbidity. Donors and recipients should be carefully selected to maximize potential for successful outcomes.

Aim To determine the appropriate target cell for assessment of anti-A titer in blood group B kidney transplant patients waiting for a deceased donor and qualify for blood group A2 (A subgroup) donors according to OPTN/UNOS guidelines. Methods 248 sera samples collected from 57 blood group B candidates (56% male, 79% African American) and tested after DTT treatment. Titers were done using A1 and A2 reagent target cells using the MTS Gel anti-IgG card method. Standard commercial blood bank reagents were used for all testing (2 donors per lot of A1 or A2 cells). The same technologist performed all titers. The titer for eligibility is ⩽ 8. Results 37 patients were eligible (titer ⩽ 8) with either A1 or A2 cells. 20 patients (35%) shown below had titers from 16 up to 128 with A1 cells. 2(4%) patients had a titer >8 with A2 cells. Of these 20 patients, the cPRA varied from 0–100% and was not correlated with anti-A titer. Sex and race was also not correlated with an anti-A titer ⩾ 8. Conclusions Patient eligibility may vary considerably depending on the target cell used. Additional clinical studies will be required to determine the optimum approach.

Transplant glomerulopathy (TG) is associated with rapid decline in glomerular filtration rate and poor outcome. We used low-density arrays with a novel probabilistic analysis to characterize relationships between gene transcripts and the development of TG in allograft recipients. Retrospective review identified TG in 10.8% of 963 core biopsies from 166 patients; patients with stable function were studied for comparison. The biopsies were analyzed for expression of 87 genes related to immune function and fibrosis by using real-time PCR, and a Bayesian model was generated and validated to predict histopathology based on gene expression. A total of 57 individual genes were increased in TG compared with stable function biopsies (P < 0.05). The Bayesian analysis identified critical relationships between ICAM-1, IL-10, CCL3, CD86, VCAM-1, MMP-9, MMP-7, and LAMC2 and allograft pathology. Moreover, Bayesian models predicted TG when derived from either immune function (area under the curve [95% confidence interval] of 0.875 [0.675 to 0.999], P = 0.004) or fibrosis (area under the curve [95% confidence interval] of 0.859 [0.754 to 0.963], P < 0.001) gene networks. Critical pathways in the Bayesian models were also analyzed by using the Fisher exact test and had P values

Obesity is an important co-morbidity within end-stage renal disease (ESRD) and renal transplant populations. Previous studies have suggested that chronic corticosteroids result in increased body weight post-transplant. With the recent adoption of steroid-sparing immunosuppressive strategies, we evaluated the effect of these strategies on body mass index (BMI) after renal transplantation. We examined 95 renal transplant recipients enrolled in National Institutes of Health clinical transplant trials over the past three yr who received either lymphocyte depletion-based steroid sparing or traditional immunosuppressive therapy that included steroids for maintenance immunosuppression. Recipients were overweight prior to transplant and no significant differences existed in pre-transplant BMI among treatment groups. Regardless of therapy, BMI increased post-transplant in all recipients. The BMI increase consisted of an average weight gain of 5.01 +/- 7.12 kg (mean, SD) post-transplant. Additionally, in a number of recipients placed on maintenance steroids, subsequent withdrawal at a mean of 100 d post-transplant had no impact on weight gain. Thus, body weight and BMI increase following kidney transplantation, even in the absence of steroids. Thus, patients gain weight after renal transplantation regardless of the treatment strategy. Steroid avoidance alone does not reduce risk factors associated with obesity in our patient population.

Mechanisms for the generation of memory CD4 T cells and their delineation into diverse subsets remain largely unknown. In this study, we demonstrate in two Ag systems, divergent generation of heterogeneous memory CD4 T cells from activated precursors in distinct differentiation stages. Specifically, we show that influenza hemagglutinin- and OVA-specific CD4 T cells activated for 1, 2, and 3 days, respectively, exhibit gradations of differentiation by cell surface phenotype, IFN-γ production, and proliferation, yet all serve as direct precursors for functional memory CD4 T cells when transferred in vivo into Ag-free mouse hosts. Using a conversion assay to track the immediate fate of activated precursors in vivo, we show that day 1- to 3-activated cells all rapidly convert from an activated phenotype (CD25highIL-7RlowCD44high) to a resting memory phenotype (IL-7RhighCD25lowCD44high) 1 day after antigenic withdrawal. Paradoxically, stable memory subset delineation from undifferentiated (day 1- to 2-activated) precursors was predominantly an effector memory (CD62Llow) profile, with an increased proportion of central memory (CD62Lhigh) T cells arising from more differentiated (day 3-activated) precursors. Our findings support a divergent model for generation of memory CD4 T cells directly from activated precursors in multiple differentiation states, with subset heterogeneity maximized by increased activation and differentiation during priming.

Alloreactive memory T cells can significantly impact graft survival due to their enhanced functional capacities, diverse tissue distribution and resistance to tolerance induction and depletional strategies. However, their role in allograft rejection is not well understood primarily due to the lack of suitable in vivo models. In this study, we use a novel approach to generate long-lived polyclonal alloreactive memory CD4 T cells from adoptive transfer of alloantigen-activated precursors into mouse hosts. We demonstrate that CD25 upregulation is a marker for precursors to alloantigen-specific memory and have created a new mouse model that features an expanded population of polyclonal alloreactive memory T cells that is distinguishable from the naive T-cell population. Furthermore, we show that alloreactive memory T cells exhibit rapid recall effector responses with predominant IFN-gamma and IL-2 production, and mediate vigorous allograft rejection. Interestingly, while we found a heterogeneous distribution of allomemory T cells in lymphoid and nonlymphoid tissues, they were all predominantly of the effector-memory (CD62Llo) phenotype. Our results present a unique model for the generation and tracking of polyclonal allospecific memory CD4 T cells in vivo and reveal insights into the distinct and robust nature of alloreactive T-cell memory.

Purpose Vascular access morbidity represents one of the most common indications for readmission in patients with end-stage renal disease (ESRD). We report the use of hybrid grafts in two patients for revision of failed vascular access for hemodialysis (HD). Case Presentations The first patient was a 45-year-old woman with ESRD who presented with an arteriovenous graft (AVG) that had required multiple interventions for maintenance in whom much of the graft was lined with covered stents. The patient presented with erosion of a stent in the AVG through the skin to the emergency department. The second patient was a 41-year-old man with ESRD who also had an AVG that had required multiple interventions for maintenance. He presented to clinic with chronic bleeding from the AVG after HD sessions. Both patients were taken to the operating room for salvage of part of the AVG through the use of hybrid vascular access grafts. The patients have passed six and three months from the procedure, respectively, without needing additional interventions. Conclusions This technique demonstrates successful use of hybrid vascular access grafts, specifically inside existing grafts in locations that contain stents utilizing the existing venous resources in that arm to carry out the surgical repair, thereby preserving venous capital.

Combined simultaneous organ transplantation has become more common as selection criteria for transplantation have broadened. Broadening selection criteria is secondary to improved immunosuppression and surgical techniques. The kidney is the most common extrathoracic organ to be simultaneously transplanted with the heart. A series of 13 patients suffering from both end-stage heart and renal failure underwent 14 simultaneous heart and kidney transplantations at Temple University Hospital between 1990 and 1999. This is the largest series reported from a single center. Three patients died during the initial hospitalization for an in-hospital mortality of 21%. Of 10 patients who left the hospital, 1-year survival was 100% and 2-year survival 75%. One patient required retransplant for rejection within the first year. Overall mortality at 1 and 2 years was 25 and 41%, respectively. Four out of nine (44%) patients greater than 5 years post-transplant were alive. Of the 10 patients who left the hospital, 66% were alive at 5 years. One patient succumbed to primary nonfunction of the cardiac allograft, while the four other deaths were secondary to bacterial or fungal sepsis. The patient's racial backgrounds were equally divided between African-American and white. These results are similar to those reported in a United Network of Organ Sharing Database (UNOS) registry analysis of 84 simultaneous heart and kidney transplants that found 1- and 2-year survival to be 76 and 67%, respectively. Simultaneous heart and kidney transplantation continues to be a viable option for patients suffering from failure of these two organ systems, although the results do not match those of heart transplant alone.

Aortic dissection is the most common catastrophic pathologic process to affect the aorta and its branch vessels. The patient was diagnosed with an acute type III aortic dissection and symptomatic occlusion of the mesenteric, renal, and iliac arteries. The patient was treated with endovascular fenestration and stenting of the iliac and renal arteries followed by open fenestration of the superior mesenteric artery, bowel resection, and cholecystectomy. Duplex ultrasonagraphy demonstrated patency of the mesenteric and iliac vessels and normal size kidneys upon discharge. The combination of traditional surgical and modern endovascular techniques may improve survival of patients with complicated type III aortic dissections.

Comprehensive care of renal transplant recipients involves multidisciplinary team starting with a thorough pretransplant evaluation and continuing as diligent postoperative care. Inherent in the nature of end-stage renal disease is accompanying comorbidity involving multiple organ systems, and many of these require surgical interventions. In this chapter we review common surgical diseases in the pretransplant period, their management, and current recommendations. The operation of renal transplantation and simultaneous kidney-pancreas transplantation along with diagnosis and management of posttransplantation surgical issues is detailed with special emphasis on surgical technique. We also discuss acute illness in the transplant recipient that require surgical consultation such as gastrointestinal hemorrhage, acute abdominal pain and describe current guidelines in their evaluation and management.

Background The outcome of HIV-infected kidney transplant recipients managed with an early corticosteroid withdrawal protocol is not known. Methods Eleven consecutive HIV-infected patients with undetectable plasma HIV RNA and more than 200/mm CD4 T cells underwent deceased-donor (n=8) or living-donor (n=3) kidney transplantation at our center. All were managed with an early corticosteroid withdrawal protocol; 9 of 11 received antithymocyte globulin and 2 received basiliximab induction. We analyzed patient and graft outcomes, acute rejection rate, HIV progression, BKV replication, infections, and urinary cell mRNA profiles. Results The median (range) follow-up was 44.5 (26-73) months. The incidence of acute rejection was 9% at 1 year and the patient and allograft survival rates were 100% and 91%, respectively. Estimated glomerular filtration rate at 1 year (mean ± SD) was 78 ± 39 mL/min/1.73 m. Plasma HIV RNA was undetectable at 24 months and none had BKV replication. Six of the 11 kidney recipients developed eight infections requiring hospitalization. Urinary cell levels of mRNA for complement components and complement regulatory proteins, cell lineage-specific proteins CD3, CD4, CD8, CTLA4, Foxp3, chemokine IP-10, cytotoxic perforin and granzyme B, and BKV VP1 mRNA were not different (P>0.05) between HIV-infected patients and HIV-negative recipients (n=22) with stable graft function and normal biopsy results. Conclusion An early steroid withdrawal regimen with antithymocyte globulin induction was associated with excellent graft and patient outcomes in HIV-infected recipients of kidney allografts. Their urinary cell mRNA profiles are indistinguishable from those of HIV-negative patients with stable graft function and normal biopsy results.

Kidney transplantation remains the most effective modality for the treatment of end-stage renal disease. The development of induction therapy has significantly reduced the incidence of acute rejection within the first six months following kidney transplantation. As a result, induction therapy is typically administered in the majority of kidney transplants. Moreover, early graft function has also improved with the advent and routine administration of induction therapy. Effective induction therapy has also expanded the donor pool as it allows for more effective utilization of marginal donor kidneys including expanded criteria donors and donors after cardiac death. It may also benefit higher immunologic risk recipients such as highly sensitized, African American, and repeat transplant patients. Poly- and monoclonal antibody agents are available for use as induction agents, including rabbit Anti-thymocyte globulin, interleukin-2 receptor antagonists, and alemtuzumab each of which have proven efficacy but have discrete advantages and disadvantages. Tailoring induction therapy to individual patient profiles provides the best opportunity for both short and long-term outcomes of the patient and allograft. Moreover, we explore the role of induction therapy with long-term steroid avoidance immunosuppression regimens in modern kidney transplantation. Overall, we review the safety and efficacy of this important group of induction agents and discuss an approach to tailoring their use for specific patients undergoing kidney transplantation.

Kidney paired donation (KPD) is a safe and effective means of transplantation for transplant candidates with willing but incompatible donors. We report our single-center experience with KPD through participation in the National Kidney Registry. Patient demographics, transplant rates, and clinical outcomes including delayed graft function (DGF), rejection, and survival were analyzed. We also review strategies employed by our center to maximize living donor transplantation through KPD. We entered 44 incompatible donor/recipient pairs into KPD from 9/2007 to 1/2011, enabling 50 transplants. Incompatibility was attributable to blood type (54.4%) and donor-specific sensitization (43.2%). Thirty-six candidates (81.8%) were transplanted after 157 d (median), enabling pre-emptive transplantation in eight patients. Fourteen candidates on the deceased donor waiting list also received transplants. More than 50% of kidneys were received from other transplant centers. DGF occurred in 6%; one-yr rejection rate was 9.1%. One-yr patient and graft survival was 98.0% and 94.8%. KPD involving participation of multiple transplant centers can provide opportunities for transplantation, with potential to expand the donor pool, minimize waiting times, and enable pre-emptive transplantation. Our experience demonstrates promising short-term outcomes; however, longer follow-up is needed to assess the impact of KPD on the shortage of organs available for transplantation.

We report the results of a large series of chain transplantations that were facilitated by a multicenter US database in which 57 centers pooled incompatible donor/recipient pairs. Chains, initiated by nondirected donors, were identified using a computer algorithm incorporating virtual cross-matches and potential to extend chains. The first 54 chains facilitated 272 kidney transplants (mean chain length = 5.0). Seven chains ended because potential donors became unavailable to donate after their recipient received a kidney; however, every recipient whose intended donor donated was transplanted. The remaining 47 chains were eventually closed by having the last donor donate to the waiting list. Of the 272 chain recipients 46% were ethnic minorities and 63% of grafts were shipped from other centers. The number of blood type O-patients receiving a transplant (n = 90) was greater than the number of blood type O-non-directed donors (n = 32) initiating chains. We have 1-year follow up on the first 100 transplants. The mean 1-year creatinine of the first 100 transplants from this series was 1.3 mg/dL. Chain transplantation enables many recipients with immunologically incompatible donors to be transplanted with high quality grafts.

1.1 Historical overview Renal transplantation remains the most effective treatment modality for end-stage renal disease. The initial results with renal transplantation were plagued with significant perioperative morbidity and high rates of immunological events. At the time, the transplant physician’s armamentarium consisted of glucocorticoids and azathioprine. As modifications and improvements in surgical technique reduced morbidity, immunological events remained formidable foes to the transplant physician. Significant efforts were undertaken to elucidate the components and mechanisms of these immunological events, ultimately leading to the discovery of lymphocytes as the primary culprits in acute rejection. Early preclinical trials demonstrated that lymphocyte-specific antibodies could be induced in animal models by injecting them with lymphocytes. The serum could then be isolated and re-injected in other animals to decrease the lymphocyte count. Thus, these experiments lead to the earliest forms of antilymphocyte antibody formulations, including antithymocyte globulin, antilymphocyte serum, and antilymphocyte globulin (Bishop et al., 1975; Cosimi et al., 1976). These initial medications had little specificity and broad effects, but their potent ability to treat acute rejection episodes led to their widespread use in the 1970’s (Cosimi, 1981a). The extensive use of these formulations exposed their various drawbacks. Because of nonspecific binding, cross-reactivity with various hematopoietic cells revealed dose-limiting side effects including thrombocytopenia, anemia, and neutropenia (Henricsson et al., 1977; Rosenberg, 1975). Additionally, the method of preparation was not standardized, thus leading to dosing variations. Because these formulations were typically made in rabbits or horses, the proteins had potential antigenic properties leading to the development of serum sickness, cytokine release syndrome, or even anaphylaxis (Niblack et al., 1987; Prin Mathieu et al., 1997; Tatum et al., 1984). The development of specific, monoclonal antibodies by Kohler and Milstein circumvented many of the drawbacks of polyclonal formulations, including lack of specificity and variability in preparation (Kohler & Milstein, 1975). Muromonab, or OKT3, was the first monoclonal antibody prepared from mouse, which is specific for cluster of differentiation 3 (CD3) (Cosimi et al, 1981b). OKT3 was effective at specifically depleting T cells from the

In kidney, liver, heart, and lung transplantation, extremes of body mass index (BMI) have been reported to influence post-operative outcomes and even survival. Given the limited data in pancreas transplantation, we sought to elucidate the influence of BMI on outcomes.We reviewed 139 consecutive pancreas transplants performed at our institution and divided them into four categories based on BMI: underweight (≤18.5 kg/m(2)), normal (18.6-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese (≥30 kg/m(2)). Parameters analyzed included post-operative complications, early graft loss, one-yr acute rejection rate (AR), non-surgical infections, and survival.Demographic data were similar between the groups. Compared with normal, only obese patients trended toward more post-operative complications (p = 0.06). Underweight and obese patients had significantly more post-operative infectious complications than normal (p = 0.0005 and p = 0.03, respectively). Obese patients had more complications requiring percutaneous drainage compared with normal (p = 0.03). Overweight and obese patients had significantly more complications requiring re-laparotomy (p = 0.03 and p = 0.048, respectively). Early graft loss, AR, non-surgical infections, and patient and graft survival rates were not different between normal and underweight, overweight, or obese patients (p 0.05).Extremes of BMI were associated with increased morbidity. Donors and recipients should be carefully selected to maximize potential for successful outcomes.

Laparoendoscopic single site surgery is a recent advance in minimally invasive urology. We report outcomes from our initial 100 consecutive laparoendoscopic single site live donor nephrectomies done by a single surgeon and provide a matched comparison of conventional laparoscopic live donor nephrectomies done by the same surgeon.From 2009 to 2010 at a tertiary referral center 100 consecutive laparoendoscopic single site live donor nephrectomies were performed by a single surgeon through a periumbilical incision using the GelPoint® system. No extraumbilical incisions or punctures were made. A retrospective review was performed using a prospectively managed database of standard perioperative and convalescent parameters. Comparison was made using a matched cohort of conventional live donor nephrectomies done by the same surgeon.Mean operative time was longer in the laparoendoscopic single site group (156 vs 130 minutes) but there was no difference in estimated blood loss or warm ischemia time. There was no difference in the complication rate between the 2 groups. Mean hospital stay and visual analog pain scores were similar in the groups but the laparoendoscopic group showed improved convalescence with faster return to work, normal activity and 100% recovery. Recipient graft function was equivalent in the 2 groups.In this retrospective, matched comparison laparoendoscopic single site live donor nephrectomy was associated with longer operative time but equivalent recipient graft function and improved convalescence. The benefits of laparoendoscopic single site surgery over conventional laparoscopy may be limited. However, with respect to live donor nephrectomy the benefits of laparoendoscopic single site surgery may nevertheless prove beneficial to decrease barriers to live organ donation.

In 2007, Rane presented the first single port nephrectomy for a small non-functioning kidney at the World Congress of Endourology. Since that time, the use of single port surgery for nephrectomy has expanded to include donor nephrectomy. Over the next two years the technique was adopted for many others types of nephrectomies to include donor nephrectomy. We present our technique for single port donor nephrectomy using the Gelpoint device. We have successfully performed this surgery in over 100 patients and add this experience to our experience of over 1000 laparoscopic nephrectomies. With the proper equipment and technique, single port donor nephrectomy can be performed safely and effectively in the majority of live donors. We have found that our operative times and most importantly our transplant outcomes have not changed significantly with the adoption of the single port donor nephrectomy. We believe that single port donor nephrectomy represents a step forward in the care of living donors.

Optimizing the possibilities for kidney-paired donation (KPD) requires the participation of donor–recipient pairs from wide geographic regions. Initially it was envisaged that donors would travel to the recipient center; however, to minimize barriers to participation and simplify logistics, recent trends have involved transporting the kidneys rather than the donors. The goal of this study was to review outcomes of this practice. KPD programs throughout the United States were directly queried about all transplants involving live donor kidney transport. Early graft function was assessed by urine output in the first 8 h, postoperative serum creatinine trend, and incidence of delayed graft function. Between April 27, 2007 and April 29, 2010, 56 live donor kidneys were transported among 30 transplant centers. Median CIT was 7.2 h (IQR 5.5–9.7, range 2.5–14.5). Early urine output was robust (>100 cc/h) in all but four patients. Creatinine nadir was

We compared postoperative complications of laparoendoscopic single site and standard laparoscopic living donor nephrectomy using a standardized complication reporting system.We retrospectively analyzed the records of consecutive patients who underwent a total of 663 laparoscopic living donor nephrectomies and 101 laparoendoscopic single site donor nephrectomies. All data were recorded retrospectively. The 30-day complication rate was compiled and graded using the modified Clavien complication scale. Multivariate binary logistic regression was used to determine independent predictors of complications.Baseline demographics were comparable between the groups. Compared to those with laparoscopic living donor nephrectomy patients who underwent laparoendoscopic single site donor nephrectomy had a shorter hospital stay and less estimated blood loss but longer operative time (p0.05) as well as higher oral but lower intravenous in hospital analgesic requirements (p0.05). Mean warm ischemia time was marginally lower in the laparoendoscopic single site donor nephrectomy group (3.9 vs 4 minutes, p = 0.03). At 30 days there was no difference in the overall complication rate between the laparoscopic living and laparoendoscopic single site donor nephrectomy groups (7.1% vs 7.9%, p0.05). There were 8 major complications (grade 3 to 5) in the laparoscopic living donor nephrectomy group but only 1 in the laparoendoscopic single site group. Multivariate binary logistic regression analysis revealed that estimated blood loss was a predictor of fewer complications at 30 days.With appropriate patient selection and operative experience laparoendoscopic single site donor nephrectomy may be a safe procedure associated with postoperative outcomes similar to those of laparoscopic living donor nephrectomy as well as low morbidity. Using a standardized complication system can aid in counseling potential donors in the future.

Background: Laparoscopic donor nephrectomy represents a significant source of allografts to patients with end- stage renal disease. Given the increasing wait-list and limited number of deceased donors, utilization of the right kidney is necessary to maximize the donor pool. Materials: We retrospectively reviewed 122 right-sided kidney donors; 73 hand-assisted laparoscopic donor nephrectomies (R-HAL-DN), 36 standard laparoscopic donor nephrectomies (R-LAP-DN), and 13 laparoendoscopic single site donor nephrectomies (R-LESS-DN). We compared these groups to matched left donors and each other, analyzing various parameters including operative times, warm ischemia time (WIT), estimated blood loss (EBL), incision length, length of stay (LOS), convalescence data and complications. Results: Right and left donors demonstrated no difference in analysis parameters in all 3 procurement techniques. When comparing all right donors total operative time and allograft extraction time were lowest in the R-LAP-DN group (p=0.003 & p=0.04, respectively). The R-LESS-DN group had the lowest EBL (p=0.06) and shortest incision length (p

Background The outcomes of single kidneys transplanted from pediatric donors into standard adult recipients (>60 kg) are unknown. Furthermore, the outcomes of single kidneys transplanted from pediatric donors less than or equal to 10 kg are also unknown. Methods We retrospectively compared 27 recipients of single kidneys from pediatric donors younger than or equal to 5 years with 69 recipients of adult cadaveric kidneys. Results The mean pediatric kidney recipient weight was 69 kg. Two-year patient and graft survival in pediatric kidney recipients was 100% and 92.5% respectively, compared with 98.5% and 89.8% in adult kidney recipients (P=NS). Mean time (days) to achieve creatinine less than 3 mg/dL was 14+/-9 compared with 14+/-20 in adult kidney recipients (P=NS). Estimated glomerular filtration rate at discharge, 6, 12, 18, and 24 months was equivalent in both cohorts. Stratifying pediatric kidney recipients by donor weight, there were no differences in acute rejection or graft loss in recipients of kidney from donors less than or equal to 10 kg (n=11; mean weight=8.85 kg), but there was a higher incidence of delayed graft function (7 of 11 vs. 1 of 16; P=0.002). Estimated glomerular filtration rate at discharge, 6, 12, 18, and 24 months was equivalent in both cohorts. Conclusions Single pediatric kidneys from donors younger than or equal to 5 years can be transplanted into standard adult recipients without compromising outcomes. Transplanting single kidneys from pediatric donors less than or equal to 10 kg into standard adult recipients is associated with an increased risk of delayed graft function; however, this does not compromise 2-year graft survival or function.

Objective To present our initial experience with right-sided laparoendoscopic single-site donor nephrectomy (LESS-RDN). Laparoendoscopic single-site (LESS) donor nephrectomy, although in its infancy, represents a potential exciting advancement over conventional laparoscopic donor nephrectomy (LDN). Almost all of the reported cases thus far have been left-sided kidneys. Methods Between August 2009 and June 2010, a total of 85 consecutive LESS DN were performed. Of these, 6 (7%) were LESS-RDN. Donor outcomes analyzed included operative time, estimated blood loss, complications, visual analog pain scores, and recovery time. Renal vein lengths were measured on preoperative computed tomography scans. Recipient outcomes analyzed included recipient creatinine at discharge and at 1 and 3 months. All data were prospectively accrued in an institutional review board-approved database. Results Five LESS-RDN were successfully performed. One case was converted to hand-assisted laparoscopy to optimize hilar dissection. The mean (± SE) operative time until allograft extraction was 89 ± 5.1 minutes, total operative time was 146 ± 12.8 minutes, warm ischemia time was 3.9 ± 0.2 minutes, and estimated blood loss was 92 ± 27 mL. The mean renal vein length was 2.7 ± 0.3 cm. There were no perioperative complications. All allografts functioned after transplantation. When compared with a matched cohort of LESS-LDN, there was no difference in allograft function at discharge and at 1 and 3 months. Conclusions Although technically challenging, LESS-RDN in experienced hands can be performed safely and should be considered as an alternative if it is the preferred kidney for transplantation.

Background Induction therapy and haplotype matching are utilized to mitigate immunologic risk in renal transplantation. The incidence of acute rejection (AR) of renal allografts has been reported to be as low as 9.3% within the first year among two-haplotype-matched siblings with no induction and triple-drug maintenance immunosuppression. We report our use of basiliximab induction in a series of two-haplotype-matched living donor renal transplants (LDRT). Methods We retrospectively reviewed 25 patients who received a two-haplotype-matched LDRT with basiliximab induction therapy. The primary endpoints were acute rejection (AR) episodes at 6 and 12 months and 1-year patient and graft survival rates. The secondary endpoints were the incidence of delayed graft function (DGF), cytomegalovirus (CMV), and BK virus (BKV). Results The rate of AR at 6 months was 0% (0/25) and 4% (1/25) at 12 months. The 1-year graft and patient survival rates were 100%. The incidence of DGF was 4% (1/25), while the incidences of CMV and BKV were 0%. Conclusion Basiliximab induction therapy with a steroid-sparing regimen yields favorable results in two-haplotype-matched LDRT, including a notable reduction in the rates of AR as compared to triple-drug maintenance immunosuppression without induction. These patients have excellent graft survival with no increased incidences of secondary infections.

We present our initial experience in 40 patients undergoing laparoendoscopic single site donor nephrectomy.We prospectively collected data on 40 consecutive patients. A single access GelPOINT™ device was inserted into the abdomen through a 4 to 5 cm periumbilical incision. We used a bariatric camera with a right angle attachment for the light cord to maximize triangulation. Parameters analyzed included warm ischemia time, operative time, estimated blood loss, visual analog pain score, time to recipient creatinine less than 3 mg/dl, and recipient creatinine at discharge home, and 3 and 6 months.A total of 38 left and 2 right donor nephrectomies were performed. Complete laparoendoscopic single site donor nephrectomy was successful in 38 cases. One left and 1 right case were converted to a hand assisted approach. Average ± SD body mass index was 26.1 ± 5.2 kg/m(2). Mean operative time to allograft extraction was 93.5 ± 27.5 minutes and mean total operative time was 166.7 ± 33.8 minutes. Average estimated blood loss was 106.7 ± 93.5 cc. Mean warm ischemia time was 3.96 ± 0.72 minutes. Mean hospital stay was 1.77 ± 0.43 days and median time to recipient creatinine less than 3.0 mg/dl was 54.2 ± 110.3 hours. Mean recipient creatinine at discharge home, and at 3 and 6 months was 1.48 ± 0.67, 1.29 ± 0.38 and 1.19 ± 0.34 mg/dl, respectively. Complications included hyponatremia in 1 patient, wound infection in 1, and a grade III laceration in an allograft that was sustained during extraction.Our initial experience with laparoendoscopic single site donor nephrectomy is encouraging. This approach to kidney donation without an extra-umbilical incision could become particularly relevant to minimize morbidity in young, healthy organ donors.