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Introduction: The purpose of this study was to compare early outcomes of de novo LCPT (once-daily extended-release tacrolimus) to IR TAC (twice-daily immediate-release tacrolimus) in a predominantly African American (AA) adult kidney transplant population., Methods: This is a single center, retrospective cohort study. Patients were divided into two cohorts: IR TAC (administered between January 1, 2017, and January 31, 2019) and LCPT (administered between February 1, 2019, and May 31, 2020). Primary endpoints were changes in tacrolimus trough levels (ng/mL) and estimated glomerular filtration rate up to 12 months post-transplantation. Clinical endpoints included graft survival, delayed graft function, biopsy-proven rejection, CMV viremia, and BK. A propensity score weighted generalized linear mixed effects model was used for analysis., Results: The rate of change in tacrolimus levels was significantly higher in the LCPT cohort compared to the IR TAC cohort at 14 days post-discharge (.2455 ng/mL per day vs. .1073 ng/mL, respectively; p < .001). Subsequently, the LCPT cohort had a slightly higher rate of decline (-.015 ng/mL per day vs. -.010 ng/mL with IR TAC; p = .0894) up to 12 months post-discharge. Although eGFR was similar between the two cohorts at 12 months post-transplant, the rate of increase was slower in the LCPT cohort (.1371 mL/min per day vs. .1852 mL/min per day, p = .0314). No significant differences were found in graft survival, DGF, BPAR, CMV, or BK infection., Conclusion: This study demonstrates that despite higher early trough levels with immediate post-transplant LCPT use, clinical outcomes are comparable to IR TAC at one-year post-transplant. Notably, LCPT use does not increase the incidence of DGF and that this formulation of CNI can be used as first line therapy post-transplant., (© 2024 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

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., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

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.

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., (© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

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/m 2 , 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/m 2 ), 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., (Copyright © 2020 by the American Society of Nephrology.)

Background: To evaluate outcomes and patency of arteriovenous grafts (AVGs) created using Gore hybrid vascular grafts in hemodialysis patients with limited venous outflow or challenging anatomy., Materials and Methods: A retrospective review was performed in two academic centers of all patients between July 2013 and December 2016 who underwent surgical AVG creation using a Gore hybrid vascular graft in a brachial artery to axillary configuration. Patient characteristics and comorbidities as well as graft patency, function, and subsequent need for percutaneous interventions were recorded., Results: Forty-six patients including 30 females (65.2%) and 16 males (34.8%) with a mean age of 63 ± 13 years were identified. The most common indications for a hybrid vascular graft were limited surgical accessibility and/or revision of existing AVG due to severe stenotic lesions at the venous outflow in 33 patients (72%). One-year primary unassisted and assisted patency rates were 44 ± 8% and 54 ± 8%, respectively, compared with 1-year secondary patency rate of 66 ± 8%. The rate of percutaneous interventions to maintain graft function and patency was approximately one intervention per graft per year., Conclusions: Access created with the hybrid vascular graft in a brachial-axillary (brachial artery to axillary vein) configuration is an acceptable option for patients with limited venous outflow reserve and challenging anatomy. Twelve-month primary and secondary patency rates and need for percutaneous interventions were comparable to traditional AVGs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction:: Centers for Medicare and Medicaid Services have determined that chronic dialysis units should have <12% of their patients utilizing central venous catheters for hemodialysis treatments. On the Eastern Shore of Maryland, the central venous catheter rates in the dialysis units averaged >45%. A multidisciplinary program was established with goals of decreasing catheter rates in order to decrease central line-associated bloodstream infections, decrease mortality associated with central line-associated bloodstream infection, decrease hospital days, and provide savings to the healthcare system., Methods:: We collected the catheter rates within three dialysis centers served over a 5-year period. Using published data surrounding the incidence and related costs of central line-associated bloodstream infection and mortality per catheter day, the number of central line-associated bloodstream infection events, the costs, and the related mortality could be determined prior to and after the initiation of the dialysis access program., Results:: An organized dialysis access program resulted in a 82% decrease in the number of central venous catheter days which lead to a concurrent reduction in central line-associated bloodstream infection and deaths. As a result of creating an access program, central venous catheter rates decreased from an average rate of 45% to 8%. The cost savings related to the program was calculated to be over US$5 million. The decrease in the number of mortalities is estimated to be between 13 and 27 patients., Conclusion:: We conclude that a formalized access program decreases catheter rates, central line-associated bloodstream infection, and the resultant hospitalizations, mortality, and costs. Areas with high hemodialysis catheter rates should develop access programs to better serve their patient population.

The practice of kidney paired donation (KPD) is expanding annually, offering the opportunity for live donor kidney transplant to more patients. We sought to identify if voluntary KPD networks such as the National Kidney Registry (NKR) were selecting or attracting a narrower group of donors or recipients compared with national registries. For this purpose, we merged data from the NKR database with the Scientific Registry of Transplant Recipients (SRTR) database, from February 14, 2008, to February 14, 2017, encompassing the first 9 years of the NKR. Compared with all United Network for Organ Sharing (UNOS) live donor transplant patients (49 610), all UNOS living unrelated transplant patients (23 319), and all other KPD transplant patients (4236), the demographic and clinical characteristics of NKR transplant patients (2037) appear similar to contemporary national trends. In particular, among the NKR patients, there were a significantly (P < .001) greater number of retransplants (25.6% vs 11.5%), hyperimmunized recipients (22.7% vs 4.3% were cPRA >80%), female recipients (45.9% vs 37.6%), black recipients (18.2% vs 13%), and those on public insurance (49.7% vs 41.8%) compared with controls. These results support the need for greater sharing and larger pool sizes, perhaps enhanced by the entry of compatible pairs and even chains initiated by deceased donors, to unlock more opportunities for those harder-to-match pairs., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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., (© 2017 Steunstichting ESOT.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

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., (Copyright© 2016 by the Terasaki Foundation Laboratory.)

Background: Renal transplant outcomes in Hispanics have been conflicting regarding acute rejection (AR) and allograft survival. Additionally, the feasibility of early corticosteroid withdrawal (ECW) regimens among Hispanics has not been adequately addressed. The purpose of this study is to report outcomes following ECW among Hispanic renal transplant recipients., Methods: We retrospectively reviewed 498 consecutive renal transplants performed at our institution between July 2005 and October 2007, including 73 Hispanic and 146 white recipients who had ECW (median follow-up 49 months). Demographics, transplant data, and outcomes of Hispanic and white recipients (WR) were analyzed., Results: Hispanics had a higher incidence of diabetes mellitus and hypertension (p = 0.007), a higher proportion of blood type O (p = 0.006), and a higher serum panel reactive antibody at the time of transplantation (p = 0.02) compared with WR. Additionally, Hispanics were on dialysis longer than WR prior to transplantation (p = 0.03). Nevertheless, the incidence of AR, patient, and graft survival rates was similar (p > 0.05) between Hispanics and WR. Ethnicity was not an independent predictor of inferior patient and graft outcomes in multivariate analyses., Conclusion: Our single-center experience indicates that ECW can be performed in Hispanic renal transplant recipients, with patient and allograft outcomes comparable with those observed in WR., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 <65 years (HR 0.25, CI 0.05-1.15, P=0.08) were associated (P<0.10) with a decreased risk of primary patency loss., 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.

Importance: Despite the potential for altruistic nondirected donors (NDDs) to trigger multiple transplants through nonsimultaneous transplant chains, concerns exist that these chains siphon NDDs from the deceased donor wait list and that donors within chains might not donate after their partner receives a transplant., Objective: To determine the number of transplantations NDDs trigger through chains., Design: Retrospective review of large, multicenter living donor-recipient database., Setting: Fifty-seven US transplant centers contributing donor-recipient pairs to the database., Participants: The NDDs initiating chain transplantation., Main Outcomes Measure: Number of transplants per NDD., Results: Seventy-seven NDDs enabled 373 transplantations during 46 months starting February 2008. Mean chain length initiated by NDDs was 4.8 transplants (median, 3; range, 1-30). The 40 blood type O NDDs triggered a mean chain length of 6.0 (median, 4; range, 2-30). During the interval, 66 of 77 chains were closed to the wait list, 4 of 77 were ongoing, and 7 of 77 were broken because bridge donors became unavailable. No chains were broken in the last 15 months, and every recipient whose incompatible donor donated received a kidney. One hundred thirty-three blood type O recipients were transplanted., Conclusion and Relevance: This large series demonstrates that NDDs trigger almost 5 transplants on average, more if the NDD is blood type O. There were more blood type O recipients than blood type O NDDs participating. The benefits of transplanting 373 patients and enabling others without living donors to advance outweigh the risk of broken chains that is decreasing with experience. Even 66 patients on the wait list without living donors underwent transplantation with living-donor grafts at the end of these chains.

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<0.0001), rejection (P<0.0001), and transplant panel reactive antibody 20% or more (P=0.03) were risk factors for graft loss. Opportunistic infections included viral in 15.3%, fungal in 1.6%, and parasitic in 0.6% of the patients. Posttransplantation malignancy occurred in 9.1% of patients., Conclusions: An early corticosteroid withdrawal regimen of rabbit antithymocyte globulin induction, tacrolimus, and mycophenolate mofetil is associated with excellent patient and kidney graft survival in an ethnically diverse population with risk factors for poor outcomes.

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.

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<0.001). One-year, three-year, and five-year patient survival was 99.3%, 94.1%, and 91.3% in recipients of older donors and 99.7%, 98.7%, and 95.4% in recipients of younger donors respectively (P=not significant). One-year, three-year, and five-year death-censored graft survival was 99.2%, 95.0%, and 93.7% in older recipients and 99.7%, 96.7%, and 95.4% in younger recipients respectively (P=not significant). Older and younger recipients demonstrated equivalent rates of vascular complications (2.7% vs. 1.2%, P=not significant) and acute rejection (7.7% vs. 9%, P=not significant). Recipients from donors aged 51 to 59 (n=95), 60 to 69 (n=42), and older than 70 years (n=6) had diminished graft function (eGFR=46±13, 44.9±16, 32.2±18.6 mL/min/1.73m(2) at 5 years respectively) compared with younger donor recipients (58.4±20.0 mL/min/1.73m(2), P<0.001). Older donors had decreased baseline renal function compared with younger donors (eGFR of 82.5±35.12 and 105.3±46.7 mL/min/1.73m(2), respectively). No progressive decline in renal function was observed in older donors (3 years after donation)., Conclusion: Older living donor kidneys can be transplanted with low perioperative risk without compromising recipient 5-year patient or graft survival or donor renal function. Younger donor kidneys have superior graft function 5 years after transplantation, highlighting the need for appropriate donor/recipient matching.

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., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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.

Background and Purpose: 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., Patients and Methods: 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 (BMI <30 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., Results: Demographic data were similar between the groups, except BMI (P>0.0001). Organ recovery time, EBL, WIT, complications, and recipient allograft function were similar between the obese LESS-DN group and the other three groups (P>0.05). Total operative time was longer in the obese LESS-DN compared with the nonobese LAP-DN (P<0.0001); however, incision length was shorter in the obese LESS-DN group compared with either LAP group (P<0.0001). Complete LESS-DN was successful in 62 (97%) cases (two obese donor cases were converted to hand-assisted laparoscopy)., Conclusions: 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.

Purpose: 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., Materials and Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We compared postoperative complications of laparoendoscopic single site and standard laparoscopic living donor nephrectomy using a standardized complication reporting system., Materials and Methods: 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., Results: 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 (p <0.05) as well as higher oral but lower intravenous in hospital analgesic requirements (p <0.05). 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%, p >0.05). 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., Conclusions: 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., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

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/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., 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., (© 2011 John Wiley & Sons A/S.)

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., (Copyright © 2011. Published by Elsevier Inc.)

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 <2.0 mg/dL in all (including the four with lower urine output) but one patient, occurring at a median of 3 days (IQR 2-5, range 1-49). No patients experienced delayed graft function as defined by the need for dialysis in the first week. Current evidence suggests that live donor kidney transport is safe and feasible., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction. Pancreas transplantation (PTx) is the only definitive intervention for type 1 diabetes. Medical advancements in diabetes care have led to an aging PTx candidate pool. We report our experience with patients ≥50 years of age undergoing PTx. Methods. We reviewed 136 consecutive PTx patients at our institution from 1996-2010; 17 were ≥50 years of age. We evaluated demographics, surgical complications, acute rejection (AR) rates, nonsurgical infections, and survival outcomes. Results. Demographic data was similar (P > .05) between groups, excluding age. The two groups had comparable major and minor surgical complication rates (P = .10 and P = .25, resp.). The older group had a lower 1-year and overall AR rate (P = .04 and P = .03, resp.). The incidence of non-surgical infections and overall patient and graft survival was similar between groups (P > .05). Conclusion. Older patients with type 1 diabetes are feasible candidates for PTx, as surgical morbidity, incidence of infections, and AR rates are low.

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., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: We present our initial experience in 40 patients undergoing laparoendoscopic single site donor nephrectomy., Materials and Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: A major unmet challenge is to reduce the islet mass needed for insulin independence in type 1 diabetic recipients after islet transplantation. The recombinant homodimer of human annexin V, diannexin, has completed a Phase II Clinical Trial in Kidney Transplantation (NCT00615966)., Methods: We developed a marginal islet mass transplantation model (10-12 islets per gram of recipient body weight) and investigated whether diannexin prevents β-cell apoptosis and improves islet graft function. Diannexin was administered to islet cell donors shortly before pancreas harvest, added to isolation reagents, and infused into recipients at the time of transplantation and repeated daily until day 4., Results: In the syngeneic marginal islet mass transplantation model, the median time needed to achieve normoglycemia was reduced from 17.0 days among untreated controls to 3.5 days among diannexin-treated recipients (P=0.004). Histologic analysis of islet grafts harvested on day 3 posttransplantation revealed decreased macrophage (44.7%±9.8% vs. 19.2%±3.2%, P=0.007) and T-cell infiltration (25.9%±5.5% vs. 9.1%±1.1%, P=0.004), and a lower rate of islet cell apoptosis (20.5%±2.8% vs. 7.6%±2.3%, P=0.01) with diannexin treatment. Expression profiling of the islet grafts showed significantly lower levels of mRNA for the proapoptotic molecule Bid, but higher levels of interleukin-6, interferon-γ, and immunosuppressive cytokine interleukin-10., Conclusions: Our findings demonstrate that diannexin improves the early function of marginal mass islet grafts, and its effects are associated with reductions in inflammatory cell infiltration and β-cell death by apoptosis after islet transplantation.

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.

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 <0.005. This study demonstrates that evaluating quantitative gene expression profiles with Bayesian modeling can identify significant transcriptional associations that have the potential to support the diagnostic capability of allograft histology. This integrated approach has broad implications in the field of transplant diagnostics.

Purpose: Intravenous heparin has traditionally been given during living donor laparoscopic nephrectomy despite the paucity of evidence supporting its use. We present the results of our experience with laparoscopic donor nephrectomy done without intraoperative systemic heparinization., Materials and Methods: We retrospectively reviewed the records of 167 consecutive laparoscopic donor nephrectomies done without intravenous heparin from July 2005 to October 2007 at our institution. We evaluated preoperative donor characteristics, intraoperative and postoperative complications, recipient renal function and graft outcomes., Results: All 138 left nephrectomies were done using a conventional laparoscopic approach while 25 of 29 right nephrectomies were done using the hand assisted technique. Warm ischemia time was approximately 3.0 minutes in each group. Mean +/- SE estimated blood loss was 183 +/- 29 ml for left and 115 +/- 16 ml for right nephrectomy. Postoperatively hematocrit decreased an average of 4.5%. There were no intraoperative complications or open conversion requirements. The postoperative complication rate was 4.8%, including 2 patients (1.2%) in whom retroperitoneal hematoma developed. Only 1 of these patients (0.6%) required blood transfusion. Two grafts (1.2%) were lost due to vascular thrombosis in the immediate postoperative period and another 2 recipients experienced delayed graft function. Average 6, 12 and 24-month serum creatinine was 1.5, 1.5 and 1.6 mg/dl, respectively. Renal allograft survival was 97% 2 years after transplantation., Conclusions: Results indicate that laparoscopic donor nephrectomy can be successfully done without systemic heparinization with few donor complications, and excellent recipient graft survival and renal function up to 2 years after transplantation., (Copyright 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

This pilot study compared the use of the Lifor Organ Preservation Medium (RTLF) at room temperature with hypothermic Belzer machine preservation solution (CMPS) and room in vitro temperature Belzer machine preservation solution (RTMPS) in a porcine model of uncontrolled donation after cardiac death (DCD). In this study, 5 porcine kidneys for each perfusate group were recovered under a DCD protocol. The kidneys were recovered, flushed, and placed onto a renal preservation system following standard perfusion procedures. The average flow rate for CMPS was 36.2 +/- 7.2549 mL/min, RTMPS was 90.2 +/- 9.7159 mL/min, and RTLF was 103.1 +/- 5.1108 mL/min. The average intrarenal resistance for CMPS was 1.33 +/- 0.1709 mm Hg/mL per minute, RTMPS was 0.84 +/- 0.3586 and RTLF was 0.39 +/- 0.04. All perfusion parameters were statistically significant (P < .05) at all time points for the CMPS when compared with both RTMPS and RTLF. All perfusion parameters for RTMPS and RTLF were equivalent for the first 12 hours; thereafter, RTLF became significantly better than RTMPS at 18 and 24 hours. It appears that both RTMPS and RTLF have equivalent perfusion characteristic for the initial 12 hours of perfusion, but LF continues to maintain a low resistance and high flow up to 24 hours. The results of this pilot study indicate that RTLF may represent a better alternative to pulsatile perfusion with CMPS and requires validation in an in vivo large animal transplant model.

Assessment of pulsatile perfusion (PP) is limited to measurements of flow (V) and resistance (R). We investigated infrared (IR) imaging during PP as a means for precise organ assessment. IR was used to monitor 10 porcine kidneys during 18 hr of PP in an uncontrolled Donation after Cardiac Death model. An IR camera (Lockheed Martin) was focused on the anterior surfaces of the kidneys. The degree of temperature homogeneity was compared with standard measurements of V and R. IR thermal images correlated with V and R (R=0.92, P<0.001). IR detected an increase in homogeneity during PP by comparing standard deviation differences before and after PP (P=0.002), which was not evident by standard measurements of V and R. Finally, IR assessment allowed for measurement of dynamic changes in perfusion.

Background: We report the influence of race on transplant outcomes in the Department of Defense (DOD) system., Methods: Retrospective cohort analysis of all kidney transplants performed at WRAMC from 1996 to 2005. Kaplan-Meier analysis was used to assess for differences in graft survival, and Cox regression was used to calculate adjusted hazard ratios for graft loss. For our analyses, we used the cutoff of 6 years (year 2000) when we introduced thymoglobulin induction; maintenance immunosuppression consisted of mycophenolate mofetil and tacrolimus, and rapid steroid taper (completed withdrawal at 6 weeks) was used for all patients., Results: There were 220 transplants (91 Blacks, 107 Caucasians and 22 Asians). Because the curve for graft survival for Blacks over time violated the proportional hazards assumption (at 6 years post-transplant), analysis was segregated into two segments. Through 6 years of follow-up, graft survival was 77% for Blacks and 81% for non-Blacks (p = 0.74 by log rank). Through 9 potential years of follow-up, graft survival for Blacks was 56% and 78% for Whites (p = 0.005). In Cox regression analysis, Black race, compared with non-Black race, was not significantly associated with graft loss at 6 years, but was significantly associated with graft loss occurring after 6 years., Conclusions: In the DOD health system, no significant differences were seen in graft survival among recipients of different races at 6 years. Black recipients who received a kidney transplant before the year 2000 showed decreased graft survival compared to non-Blacks. This was consistent with change in immunosuppressive regimen in our institution with the introduction of thymoglobulin induction and maintenance therapy with tacrolimus, mycophenolate mofetil and withdrawal of prednisone at 6 weeks.

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-gamma 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 (CD25(high)IL-7R(low)CD44(high)) to a resting memory phenotype (IL-7R(high)CD25(low)CD44(high)) 1 day after antigenic withdrawal. Paradoxically, stable memory subset delineation from undifferentiated (day 1- to 2-activated) precursors was predominantly an effector memory (CD62L(low)) profile, with an increased proportion of central memory (CD62L(high)) 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.

Pancreas transplant has become a reliably predictable treatment and cure for patients with type 1 diabetes mellitus and hypoglycemic unawareness or renal failure. During the past 2 years, the use of enteric drainage has been shown to decrease morbidity over traditional bladder drainage, and the use of the portal system for venous drainage continues to be explored. Technically, the use of circular staplers, over a hand-sown anastomosis for duodenal drainage, has gained popularity, and alternative arterial reconstruction methods have been developed. Living donor pancreas and kidney transplants are also becoming more common throughout the world. In the area of immunosuppression, steroid-free protocols, now commonplace in kidney transplants, are being applied successfully to pancreas transplantation. Finally, the benefit of solitary pancreas and pancreas after kidney transplantation has been questioned, and a more complete analysis of pancreas alone and pancreas after kidney transplants is anticipated in the near future.

Machine pulsatile perfusion for whole pancreas preservation might improve yield, viability, and function of human islets recovered after prolonged cold ischemia times. Four human pancreata were procured from cadaver donors (1 non-heart-beating donor) and stored in cold University of Wisconsin (UW) solution for a mean 13 hours prior to placement on a machine pulsatile perfusion device. The four pancreata were perfused for 4 hours with UW solution before undergoing islet isolation. Islets were quantified, viability was assessed, and insulin secretion was measured. Results were compared with nonpumped islet isolations stratified for cold ischemia time (CIT) <8 hours or cold ischemia time >8 hours. The islet yield for the four pumped pancreata was 3435 (+/-1951) islet equivalents/gram pancreas tissue (IEQ/g), compared with a mean yield of 5134 (+/-2700) IEQ/g and 2640 (+/-1000) IEQ/g from pancreas with <8 hours and >8 hours CIT, respectively. The mean viability after machine pulsatile perfusion was 86% (vs 74% and 74% for the <8 hour and >8 hour CIT groups). The mean viable yield (total yield x viability) was 2937 IEQ/g for machine perfusion, compared with 3799 IEQ/g and 1937 IEQ/g from pancreata with <8 hours and >8 hours CIT, respectively. The insulin secretion index of islets after machine perfusion was 6.4, compared with indices of 1.9 and 1.8 for the <8 hour and >8 hour CIT groups. This preliminary data indicates that low-flow machine pulsatile perfusion of pancreata with prolonged cold ischemia time can result in excellent yield, viability, and function.

Purpose: To ascertain the extent to which ophthalmologic interventions have been evaluated in value-based medicine format., Methods: Retrospective literature review. Papers in the healthcare literature utilizing cost-utility analysis were reviewed by researchers at the Center for Value-Based Medicine, Flourtown, Pennsylvania. A literature review of papers addressing the cost-utility analysis of ophthalmologic procedures in the United States over a 12-year period from 1992 to 2003 was undertaken using the National Library of Medicine and EMBASE databases. The cost-utility of ophthalmologic interventions in inflation-adjusted (real) year 2003 US dollars expended per quality-adjusted life-year (dollars/QALY) was ascertained in all instances., Results: A total of 19 papers were found, including a total of 25 interventions. The median cost-utility of ophthalmologic interventions was 5,219 dollars/QALY, with a range from 746 dollars/QALY to 6.5 million dollars/QALY., Conclusions: The majority of ophthalmologic interventions are especially cost-effective by conventional standards. This is because of the substantial value that ophthalmologic interventions confer to patients with eye diseases for the resources expended.

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.