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Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HR pancreas = 1.04, p = 0.93; HR kidney = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (p pancreas = 0.57; p kidney = 0.41). T2D had a significantly lower incidence of de novo DSA at 1 year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients., Competing Interests: The authors of this manuscript have conflicts of interest to disclose as described by the Transplant International. JO is co-founder of, has equity interest in and serves as Chair of the Scientific Advisory Board of Regenerative Medical Solutions, Inc. He receives clinical trial support from Veloxis Pharmaceuticals, CareDx Transplant Management, Inc., Natera, Inc. and Vertex Pharmaceuticals, Inc. DK reports serving as a scientific advisor for, or member of, eGenesis, and receiving research funding from Medeor Pharma and the National Institutes of Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martinez, Pham, Wang, Stalter, Welch, Leverson, Marka, Al-Qaoud, Mandelbrot, Parajuli, Sollinger, Kaufman, Redfield and Odorico.)

Objectives: This study aimed to find the association between immediate postoperative increases in pancreatic enzymes and posttransplant complications among pancreas transplant recipients (PTRs)., Methods: We analyzed all PTRs transplanted at the University of Wisconsin between June 2009 and September 2018. Enzyme levels were presented as a ratio of absolute numbers to the upper limit of normal value, with value >1 considered as abnormal. We specifically evaluated bleeding, fluid collections, and thrombosis complications based on the amylase or lipase ratios on day 1 (Amylase1, Lipase1) and maximum ratios within 5 days of transplant (Amylasemax, Lipasemax). For early complications, we focused on technical complications that occurred within 90 days of transplant. For long-term outcomes, we assessed patient and graft survival, and rejections., Results: There were a total of 443 PTRs, 287 were simultaneous pancreas and kidney recipients, and 156 were solitary pancreas recipients. Higher Amylase1, Liplase1, Amylasemax, and Lipasemax were associated with an increase in early complications, mainly need for pancreatectomy, fluid collections, bleeding complications, or graft thrombosis, particularly in the solitary pancreas group., Conclusions: Our finding suggests that cases of early perioperative enzyme increase merit consideration for early imaging investigation to mitigate detrimental outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The effects of HLA mismatching on pancreas outcomes among pancreas after kidney (PAK) recipients are undefined. Outcomes might potentially differ depending on whether there is a mismatch between pancreas donor and recipient (PD-R) or pancreas donor and kidney donor(PD-KD). All primary PAK at our centre were included in this study. Patients were divided into two groups based on the degree of HLA mismatching: low (L-MM) as 0-4 and high (H-MM) as 5-6. We analysed all (N = 73) PAK for PD-R mismatch and the subset of PAK for PD-KD mismatch (N = 71). Comparing PD-R L-MM (n = 39) and H-MM (n = 34) PAKs, we observed no difference in the rate of pancreas graft failure. There was also no difference in the rate of rejection (L-MM 33% vs. H-MM 41%) or the severity of rejection. However, we observed a significantly (P < 0.01) shorter time to acute pancreas rejection in the H-MM group (6.8 ± 8.7 mo) versus the L-MM cohort (29.0 ± 36.2 mo) (P < 0.001). Similar to the PD-R mismatched cohort, we did not observe a detrimental effect of HLA mismatching on graft outcomes in the PD-KD cohort; time to rejection was again shorter in the H-MM subset. In this study, we found no impact of HLA mismatch on either pancreas graft survival or rejection rates, though rejection occurred earlier in high mismatched PAK transplants., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Studies have found similar outcomes of Simultaneous Pancreas-Kidney transplantation (SPKT) in patients with Type 2 (T2D) and Type 1 diabetes (T1D). However, there are scarce data evaluating the association of recipient factors such as age, BMI, or pretransplant insulin requirements with outcomes, thus the criteria for the optimal recipient selection remains unclear. In this study, 284 T1D and 39 T2D patients, who underwent SPKT between 2006 and 2017 with 1 year of follow-up at minimum, were assessed for potential relationship of pretransplant BMI and insulin requirements with posttransplant diabetes and pancreatic graft failure. Kaplan-Meier analysis showed similar rates of freedom from posttransplant diabetes (94.7% T2D vs. 92.3% T1D at 1 yr, and 88.1% T2D vs. 81.1% T1D at 5 yrs) and graft survival (89.7% T2D vs. 90.4% T1D at 1 yr, and 89.7% T2D vs. 81.2% T1D at 5 yrs). There was no significant association between BMI or pretransplant insulin requirements with posttransplant diabetes occurrence in either T1D (p = .10, .43, respectively) or T2D (p = .12, .63) patients in the cohort; or with graft failure (T1D: p = .40, .09; T2D: p = .71, .28). These observations suggest a less restricted approach to selective use of SPKT in patients with T2D., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: Despite advances in surgical techniques and organ preservation, transplant ureteric strictures remain a common complication in kidney transplantation. A variety of endourological and surgical techniques have been utilized; however, there is a lack of consensus on the optimal modality in dealing with these complex cases., Materials and Methods: We present challenging ureteral reconstruction cases after failed attempts at ureteral dilatation, failed conventional open repairs, and/or with bladder dysfunction., Results: All renal allografts were salvaged by successful use of bladder Boari flap and intestinal segment interpositions/diversions., Conclusions: Operative repair remains the most durable and successful approach, and minimally invasive options should be reserved for nonsurgical candidates, with consideration of a single attempt in patients with early, distal, short (<2 cm), nonischemic strictures.

Despite good organ quality, pancreata from extremely small pediatric donors (<30 kg) are generally avoided by many centers because of concerns of reduced islet cell mass and early technical failure. Therefore, we sought to compare the outcomes of small pancreas grafts (<30 kg) to those from higher weight donors from transplants performed between 1994 and 2015 (n = 1183). A total of 33 pancreata were from donors' ≤30 kg (3%), with a mean weight of 23.8 kg and mean age of 7.8 years. Patient survival was similar at 1, 5, and 10 years between recipients of ≤30 and >30 kg donors (≤30 kg: 96.8%, 86.8%, and 78.1% vs. >30 kg: 96.8%, 89.5%, and 79.1%, P = 0.5). Pancreas graft survival at 1, 5, and 10 years was also similar, ≤30 kg: 93.9%, 73.2%, and 61.0% vs. >30 kg: 87%, 73.3%, and 58.3% (P = 0.7). This graft survival pattern was also seen when comparing pancreata from ≤20 kg donors to those from >20 to 30 kg. Cause of graft loss, and metabolic and physiologic outcomes did not differ between the groups. After assessing the impact of donor weight as a continuous variable and calculating recipient-to-donor weight ratio (RDWR), we observed no effect of donor weight on patient and graft outcomes., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Objectives: Nutcracker syndrome is rare, and a proportion of patients with this syndrome continue to have intractable pain and symptoms. Due to the heterogeneity of patients' chief complaints and symptoms, the surgeon's preferred approach may be inherently different but is of paramount importance to the outcome., Materials and Methods: We present 4 cases in which renal autotransplant with extraction and ligation of previously placed gonadal coils was performed following previously attempted renal vein stenting or combined renal vein transposition followed by renal vein stenting., Results: Autotransplant resulted in flank pain resolution with improvement in symptoms associated with pelvic congestion syndrome., Conclusions: The approach to such cases requires meticulous and adequate vena cava exposure, with preparation for potential caval reconstruction. No firm inferences can be made from such a small series; however, we believe in renal autotransplant as first-line therapy, and failure after an initial renal vein stent should be salvaged by renal autotransplant over further endovascular attempts.

In the early experience of pancreas transplantation, bladder drainage was favored, but it often caused urologic, metabolic, and infectious complications that necessitated conversion to enteric drainage. Long-term graft survival after enteric conversion and the impact of time interval from transplantation to enteric conversion on graft survival is poorly understood. We studied all bladder-drained first-time pancreas transplantations performed at the University of Wisconsin from 1985 to 2000. Time to conversion was estimated with the Kaplan-Meier technique, whereas risk factors associated with conversion were estimated via a time-varying Cox proportional hazards model. Of 386 bladder-drained pancreata, 162 (41.9%) eventually required enteric conversion, 29 (17.9%) within the first year. Median time to conversion varied by indication: 0.68 years for surgical, 3.1 years for urologic, and 2.7 years for metabolic disorders. In a time-varying Cox model adjusting for donor and recipient factors, enteric conversion did not affect the risk of pancreas graft loss (hazard ratio [HR] 0.86, P = .26). Kidney survival was not associated with enteric conversion. When necessary due to symptoms or complications, enteric conversion of bladder-drained pancreata is safe and does not affect overall graft survival. This relationship appears to be true no matter when the conversion is performed., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: The objectives of this pilot study were twofold. First, we aimed to elicit whether the "UW-LPHS test" definitively localizes pain from patients' loin pain hematuria syndrome to the ureter and thus proves our hypothesis. Second, we aimed to understand whether a positive UW-LPHS test predicts a successful outcome after renal autotransplant., Materials and Methods: The UW-LPHS test is described in detail in this manuscript. Briefly, 0.5% bupivacaine is injected into the ureter of the affected side and kept there using a balloon catheter for 5 minutes., Results: All six patients studied had complete pain relief at a mean follow-up of 9.2 months after renal autotransplant. All patients were successfully weaned from opioids and have returned to a normal lifestyle., Conclusions: The UW-LPHS test can be used to predict renal autotransplant outcomes and should be applied to all patients who are being considered for this operation.

We aimed to evaluate the influence of urological complications occurring within the first year after kidney transplantation on long-term patient and graft outcomes, and sought to examine the impact of the management approach of ureteral strictures on long-term graft function. We collected data on urological complications occurring within the first year posttransplant. Graft survivals, patient survival, and rejection rates were compared between recipients with and without urological complications. Male gender of the recipient, delayed graft function, and donor age were found to be significant risk factors for urological complications after kidney transplantation (P < .05). Death censored graft survival analysis showed that only ureteral strictures had a negative impact on long-term graft survival (P = .0009) compared to other complications. Death censored graft survival was significantly shorter in kidney recipients managed initially with minimally invasive approach when compared to the recipients with no stricture (P = .001). However, graft survival was not statistically different in patients managed initially with open surgery (P = .47). Ureteral strictures following kidney transplantation appear to be strongly negatively correlated with long-term graft survival. Our analysis suggests that kidney recipients with ureteral stricture should be managed initially with open surgery, with better long-term graft survival., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: In a diabetic, uremic kidney transplant recipient that may receive a future pancreas after kidney (PAK) transplant, the kidney is typically implanted on the left side in anticipation of the subsequent pancreas transplant on the right side. In this study, we sought to determine if ipsilateral PAK (iPAK) is as safe as contralateral PAK (cPAK)., Methods: The 115 PAK transplants (iPAK n = 57, cPAK n = 58) were performed from 1997-2010 and results were compared between the groups., Results: Kidney graft survival and pancreas graft survival was similar between the two groups. Kidney graft function according to serum creatinine and eGFR was not different between the cPAK and the iPAK groups and there were no episodes of kidney graft thrombosis in either group. Subgroup analyses focusing on donor source also did not show worse outcomes for graft survivals in iPAK group when compared to cPAK group., Conclusions: Pancreas and kidney graft survival in PAK transplants is unaffected by the surgical procedure and iPAK is safe., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Literature on the behavior of cystic lesions in pancreas transplants is scarce, and hence a better understanding is warranted. Data on recipients and their respective donors that underwent simultaneous kidney and pancreas, pancreas transplant alone, and pancreas after kidney between 1994 and 2015 were reviewed (n = 1185). Cystic lesions of the transplant pancreas developed in 22 patients (1.8%): 12 pseudocysts, 2 cysts/remnants, 4 intraductal papillary mucinous neoplasms (IPMN), 2 adenocarcinomas, 1 low-grade intraepithelial pancreatic neoplasia, and 1 case of polycystic kidney disease. The median size was 3.6 cm (1.6-5.5 cm), and occurred at a median time of 65.5 months (2-183 months) posttransplant. The median age of the graft at time of diagnosis was 42 years (25.7-54.5), with 17 of 22 grafts (77%) functioning at time of diagnosis. Triggers for investigation were elevations in pancreatic enzymes, re-admissions for abdominal pain, and incidentalomas. High-resolution imaging and diagnostic biopsy/aspiration with ancillary tests were the main diagnostic tests. Most pseudocysts were managed by percutaneous drainage, and although no firm inference can be made from such a small series, we have observed that the behavior and management of IPMN and adenocarcinoma in the pancreas graft appears congruent to that of the native pancreas., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

It is commonly assumed that in simultaneous pancreas and kidney (SPK) recipients, rejection of the two organs is concordant. As a result, concurrent biopsies of both organs are rarely performed and there are limited histological data on how often rejection is in fact discordant. We reviewed all SPK recipients transplanted at the University of Wisconsin between January 01, 2001, and December 31, 2016, that underwent biopsy of both organs. We included all patients whose biopsies were within 30 days. If patients were treated for rejection between biopsies, they were excluded if the biopsies were more than 4 days apart. Ninety-one simultaneous biopsies were performed within 30 days of each other, and 40 met our inclusion criteria. A total of 25 (62.5%) patients had concordance of biopsy findings: 11 had rejection of both organs, and 14 had no rejection of either organ. The other 15 (37.5%) were discordant for rejection, with 10 having pancreas-only rejection and five kidney-only rejection. It was striking to find that four of the 11 patients with concordance for rejection (36%) had different types (AMR, ACR, or mixed) of rejection in the two organs. This large series of simultaneous pancreas and kidney biopsies demonstrates the continued utility of performing biopsies of both organs., (© 2017 Steunstichting ESOT.)

Loin Pain Hematuria Syndrome (LPHS) remains a rare disease but has a significant impact on those affected by it. Patients diagnosed with LPHS experience severe, constant or intermittent flank pain that radiates to the groin and may be exacerbated even by a gentle touch. These patients often require significant narcotic regimens for pain control and are unable to maintain a functional lifestyle. Previously, diagnosis has been made based on clinical presentation. One treatment for this syndrome is renal autotransplant; however, success rates are varied. Therefore, patient selection for this procedure is important. We have developed the UW-LPHS test as a diagnostic maneuver in order to determine which patients with LPHS would benefit from renal autotransplant. To perform this diagnostic test, bupivacaine is instilled into the ureter on the affected side and left to dwell. Patients who experience pain relief following this test are deemed to benefit from renal autotransplant. Here we describe this novel diagnostic test and initial success rates following renal autotransplant.

Background: Many strategies regarding timing of native nephrectomies exist for patients with symptomatic polycystic kidney disease (PCKD)., Methods: This is a single-center, retrospective study of 594 adults with PCKD who had renal transplants from 1994 to 2014. Three groups were analyzed: renal transplant-only recipients (tx alone), recipients of simultaneous bilateral nephrectomies and transplant (simultaneous), and recipients with pretransplant bilateral nephrectomies (pre). The primary outcome was graft survival. Secondary outcomes included postoperative complications., Results: Five hundred sixty-five adults with PCKD received kidney transplants (303 tx alone, 161 simultaneous, 27 pre). Ten-year posttransplant graft survival was 68.5%, 63.6%, and 65.7% for tx alone, simultaneous, and precohorts (P = 0.86). No statistically significant differences were observed in rates of postoperative ileus, deep vein thrombosis, small bowel obstruction, urinary stricture, urine leak, hernia formation, and delayed graft function. More wound complications were seen in prepatients (25.9% vs 11.1% tx alone, 5.1% simultaneous; P = 0.03), whereas simultaneous patients had a lower incidence of lymphocele (1.3% vs 11.1% pre, 10.2% tx-alone; P = 0.002). Importantly, simultaneous patients had more renal vascular thromboses (4.4% vs 1.3% tx alone, 0% pre; P = 0.04). 16.3% of renal transplant alone patients required nephrectomy at 10 years follow-up. Twenty-nine patients were referred for transplant having had nephrectomies and were ultimately not transplanted. In 4 of these patients who had data available for analysis, the mean panel-reactive antibody significantly increased after nephrectomy was performed., Conclusions: Simultaneous bilateral nephrectomy can be safely performed at the time of renal transplantation, however, carries a significantly increased risk of renal vascular thrombosis.

Background: Hemoglobin A1C (HbA1c) levels are often obtained in potential pancreas graft donors to assess the overall long-term functional glycemic control or the possibility of unrecognized diabetes. Although routinely measured, the impact of donor HbA1c levels on pancreas graft outcomes has not been reported. Here, we researched the relationship between donor HbA1c levels and postoperative pancreas graft survival., Methods: Data from 266 pancreas transplant patients including 182 simultaneous kidney-pancreas and 84 pancreas alone transplants were reviewed for the study. The patients were separated into groups according to their HbA1c levels (5 groups: HbA1c < 5.0, 5.0-5.4, 5.5-5.9, ≥6.0 % and not available, or 2 groups: HbA1c <5.7, ≥5.7%). Overall, death-censored and technically successful pancreas graft survival and rejection rates of each group were compared. In the case of technically successful graft survival, graft losses due to technical problems in the first 60 days were excluded., Results: All groups were similar with regard to donor variables including age, sex, ABO blood type, ethnicity, donor type and recipient variables including recipient age, sex, induction agents and maintenance treatment. Mean follow-up time was 4.2 ± 1.97 years. The overall graft survivals and death censored graft survivals among groups were not statistically different from one other (P > 0.05). Additionally, excluding early technical losses in 18 patients did not reveal any differences in graft survivals. Patient survival and biopsy-proven acute rejections were statistically similar among HbA1c strata., Conclusions: This univariate retrospective analysis of a single center/organ procurement organization use of HbA1c shows that donor HbA1c levels between 3.5 and 6.2 in otherwise transplantable pancreata are not associated with different short-term outcomes.

The rapid rise of transplantation over the past 60 years has been marked by a number of critical milestones. Donation after circulatory death (DCD) has played an important role in the development of this young field. Although early observations by Dr. Tom Starzl touched on the importance of warm ischemic time, new and exciting data may be changing our views of ischemia. Indeed, as we learn more about the importance of time-to-death for DCD donors after circulatory death, the hemodynamic changes experienced by DCD donors, and the other physiologic perturbations surrounding all forms of death, we are beginning to drill down to the factors that drive recipient outcomes after deceased donor transplant. As far as the future? Only time will tell.

Pancreas transplant outcomes have progressively improved. Despite this, some centers have continued to employ historical age limits for pancreas transplant candidates. We sought to determine the importance of chronological age in determining patient and graft survival rates after pancreas transplantation. A single-center, retrospective study of adult, deceased donor simultaneous pancreas and kidney (SPK) and solitary pancreas transplants (SP, including pancreas transplant alone and pancreas after kidney transplants) in recipients ≥ 55 years (55 + ), occurring between July 1, 1999, and June 30, 2012, was performed. Seven-hundred and forty patients underwent pancreas transplantation, of which 28 patients were 55 + . Patient survival was comparable for younger and older pancreas transplant recipients. Both non-death-censored and death-censored pancreatic graft survival rates were similar in younger and in older patients. Patients aged 45-54 and those aged 55 +  had more frequent cardiovascular events than younger pancreas transplant recipients. There was no difference in renal graft survival for SPK patients when compared with diabetic kidney transplant alone recipients aged 55 years and older. Older pancreas transplant recipients had acceptable long-term patient and graft survival rates, although complications may occur. Chronological age alone should not exclude a patient for pancreas transplant candidacy., (© 2016 Steunstichting ESOT.)

Objective: The objective of this study was to determine the fate of patients who attempted to donate organs after circulatory death (DCD) using a standardized DCD protocol., Background: Successful donation is not always possible after attempted DCD., Methods: Data were collected for all DCD donors between 1/2011 and 9/2014. DCDs were carried out using a uniform protocol at a single-center organ procurement organization., Results: During the timeframe considered, DCD donation was attempted in 169 patients. In 46 patients (27.2%), no organs were recovered because the patients did not die within 2 hours. Successful donation was more likely if withdrawal of support occurred in the operating room versus the intensive care unit (P = 0.006). Time from extubation to death was available for 161/169 donors (95.3%). Of 161 donors, 111 (66.9%) died in under 1 hour. The mean time from withdrawal of support to patient death for unsuccessful donations was 33 hours, 37 minutes (range, 24 minutes-242 hours) versus 29 minutes (range, 5 minutes-2 hours, 4 minutes) for successful donations. Twenty-seven patients who unsuccessfully donated (67.5%) died within 24 hours. Were unsuccessful donations converted to successful donations, as many as 837 abdominal transplants could have been carried out in the United States, during the study period., Conclusions: DCD is an important form of organ donation. A large number of abdominal transplants are not possible due to unsuccessful DCD organ donation. It may be useful to explore DCD donor family satisfaction to identify other options for improving DCD donation.

Background: Recent evidence suggests that de novo donor-specific antibodies (dnDSA) are associated with antibody-mediated rejection (ABMR) and graft failure after kidney transplantation. The effects of induction immunosuppression on dnDSA are unknown., Methods: The study population comprised 114 consecutive moderately sensitized (positive DSA and negative flow crossmatch) recipients who received deceased donor renal transplants between December 2009 and November 2011. Patients were divided into two groups based on induction immunosuppression: antithymocyte globulin (ATG) (n=85) or basiliximab (n=29) and were followed up for 36 months., Results: Patients in the ATG group received a mean dose of 4.98 mg/kg ± 7.9 mg/kg, had a significantly higher PRA, and received more plasmapheresis and IVIG at the time of transplant. The incidence of dnDSA (P=0.02, HR=0.33, 95% CI 0.09-1.24) and ABMR (P=0.002, HR=0.2, 95% CI 0.04-0.87) was significantly lower in the ATG group. In multivariate regression analyses, ATG induction was the single most important variable associated with both ABMR and dnDSA., Conclusions: In moderately sensitized deceased donor renal transplant recipients, induction with ATG is associated with a reduction in the occurrence of dnDSA and ABMR when compared with basiliximab.

Antibody-mediated rejection (AMR) after pancreas transplantation is a recently identified entity. We describe the incidence of, risk factors for, and outcomes after AMR, and the correlation of C4d immunostaining and donor-specific antibody (DSA) in the diagnosis of AMR. We retrospectively analyzed 162 pancreas transplants in 159 patients who underwent 94 pancreas allograft biopsies between 2006 and 2009. Univariate and multivariate analyses were performed to evaluate risk factors for pancreas graft AMR. One-year rejection rates and survival after rejection were calculated by Kaplan-Meier methods. AMR occurred in 10% of patients by 1-year posttransplant. Multivariate risk factors identified for AMR include nonprimary simultaneous pancreas-kidney (SPK) transplant, primary solitary pancreas (PAN) transplant and race mismatch. After pancreas rejection, patient survival was 100% but 20% (8 of 41) of pancreas grafts failed within 1 year. Graft survival after acute cellular rejection (ACR), AMR and mixed rejection was similar. Of biopsies that stained >5% C4d, 80% were associated with increased Class I DSA. In summary, AMR occurs at a measurable rate after pancreas transplantation, and the diagnosis should be actively sought using C4d staining and DSA levels in patients with graft dysfunction, especially after nonprimary SPK and primary PAN transplantation., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The survival benefit of transplanting hepatitis C (HCV)-positive donor kidneys into HCV-positive recipients remains uncertain. The purpose of this study was to assess the effect of HCV-status of the donor (D) kidney on the long-term outcomes in kidney transplant recipients (R). We evaluated 2169 consecutive recipients of deceased-donor kidney transplants performed between 1991 and 2007. The following HCV cohorts were identified: D-/R- (n = 1897), D-/R+ (n = 59), D+/R- (n = 118), and D+/R+ (n = 95). Patients were followed for a mean of 6.02 (standard deviation = 4.26) yr. In a mulitvariable Cox-proportional hazards model, D+/R+ cohort had significantly lower patient survival (adjusted-hazard ratio [HR] 2.1, 95% CI [1.4-2.9]) with respect to the reference D-/R- group, whereas mortality was not increased in D-/R+ group. The rate of graft loss was increased in both D+/R+ and D-/R+ but was comparable with each other (adjusted-HR 1.8, 95% CI [1.4-2.5]) vs. adjusted-HR 2.0, 95% CI [1.4-2.8], respectively). D-/R+ cohort experienced significantly higher rate of rejection (adjusted-HR 1.7, 95% CI [1.2-2.5]) and chronic allograft nephropathy (adjusted-HR 2.1, 95% CI [1.2-3.7]). Neither donor nor recipient HCV-status impacted the risk of recurrent or de novo GN. Transplanting HCV-positive kidneys as opposed to HCV-negative kidneys into HCV-positive recipients provided similar graft survival but compromised patient survival in the long term., (© 2012 John Wiley & Sons A/S.)

Background and Objectives: Expanded-criteria donor (ECD) kidneys are used to expand the number of deceased-donor kidney transplants, often for elderly recipients. This study sought to determine whether older recipients had significantly worse outcomes from receiving ECD kidneys and whether outcomes of ECD versus standard-criteria donor (SCD) kidneys differed in younger recipients., Design, Setting, Participants, & Measurements: This is a single-center, retrospective review of all primary deceased-donor kidney transplantations performed between 2000 and 2005. Group 1 consisted of patients ≥60 years of age (n=189) who received an ECD (n=96) or an SCD (n=93) kidney. Group 2 consisted of patients 40-59 years of age (n=370) who received an ECD (n=105) or an SCD (n=265) kidney., Results: Older recipients (group 1) who received ECD kidneys demonstrated significantly shortened 5-year actuarial patient and graft survival rates compared with older recipients of SCD allografts. Group 1 ECD recipients also had significantly worse outcomes than younger (group 2) ECD recipients. In multivariate analysis, ECD kidneys remained an independent predictor of poorer outcome in group 1., Conclusions: Morbidity and mortality were increased in elderly recipients of ECD kidneys. These findings may have implications in kidney allocation policy developments that encourage placement of ECD kidneys for older recipients.

Introduction: We have performed 113 renal and 28 isolated pancreas retransplants in our cohort of more than 1200 prior simultaneous pancreas and kidney (SPK) recipients. On the basis of these experiences, we began performing repeat SPK in prior SPK recipients (n = 9)., Methods: This retrospective review summarizes our experience with repeat SPK transplantation in prior SPK recipients. Mean age at retransplant was 39 yr; mean interval to retransplant was 7.8 yr. Thirty-three percent were pre-dialysis. Eighty-nine percent of patients underwent transplant nephrectomy (five during the repeat SPK and three prior to it), and 78% underwent transplant pancreatectomy (four during the repeat SPK and three prior to it). Enteric drainage was performed in all repeat SPKs., Results: Median length of stay was 11 d. Perioperative complications included the following: renal artery thrombosis (1), pancreatic portal venous thrombosis (1), enteric leak (1), and hematoma (2). Overall pancreatic allograft survival was 78% at one yr and 67% at two yr. Overall renal allograft survival was 89% at one yr and 78% at two yr. Patient survival at one and three yr was 100%., Conclusions: Survival of repeat SPK allografts is acceptable despite the increased technical and immunologic demands of retransplantation. Graftectomy prior to or at the time of retransplantation is often necessary., (© 2011 John Wiley & Sons A/S.)

Between 1 January 2002 and 31 December 2007, our center performed 1687 adult renal transplants. A retrospective analysis was performed to compare outcomes between patients receiving alemtuzumab (n = 632) and those receiving either basiliximab (n = 690) or thymoglobulin (n = 125). Patients receiving alemtuzumab were younger (49 vs. 51 years, P = 0.02), had fewer HLA matches (1.7 vs. 2.0, P < 0.0001), were more likely to have a cytomegalovirus (CMV) donor(+)/recipient(-) transplant (22% vs. 17%, P = 0.03) and were less likely to receive a living donor allograft (32% vs. 37%, P = 0.04). Alemtuzumab recipients were less likely to receive tacrolimus (35% vs. 47%, P < 0.0001). The 1-, 3-, and 5-year cumulative incidence of antibody-mediated rejection (AMR) in alemtuzumab-treated patients was 19%, 24%, and 27%, vs. 11%, 15%, and 18% for the other group (P < 0.0001). The 1-, 3-, and 5-year allograft survival in the alemtuzumab group was 88%, 75%, and 67%, vs. 91%, 82%, and 74% for the other group (P < 0.0001). Patient survival was equivalent. Alemtuzumab was an independent risk factor for living donor allograft loss (HR 2.0, P = 0.004), opportunistic infections (HR 1.3, P = 0.01), CMV infections (HR 1.6, P = 0.001), and AMR (HR 1.5, P = 0.002). The significantly worse graft survival in the alemtuzumab cohort may be due to the increased rates of AMR and infectious complications., (© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.)

Background: Tolerance to noninherited maternal antigens has provided clinical advantage when kidney transplants are exchanged between siblings but not when mother herself is the donor. This paradox prompted us to revisit the "two-way" hypothesis of transplant tolerance--that the immune status of both the organ recipient and the organ donor critically influences allograft outcome., Methods: We obtained peripheral blood monocyte cells from 29 living donor-recipient pairs before transplant and used the trans-vivo-delayed type hypersensitivity assay to measure immune regulation in both the recipient antidonor and donor antirecipient directions., Results: We found preexisting bidirectional regulation in all human leukocyte antigen (HLA)-identical sibling pairs tested (7/7), and one half (9/18) of the HLA haploidentical pairs. No significant regulation was found in four control living unrelated and two HLA haploidentical living-related donor recipient pairs, whereas unidirectional regulation was found in the remaining seven haploidentical pairs. Of the nine HLA haploidentical transplants with unidirectional or no pretransplant regulation, seven had an acute rejection episode and four of these experienced graft loss. In contrast, of the nine HLA haploidentical transplants with bidirectional regulation, only one had rejection. Renal function for the latter group was similar to HLA-identical kidney recipients at 3 years posttransplant. Significantly (P<0.05) lower mean serum creatinine values in bidirectional regulators were noted as early as 4 months and this difference became more pronounced at 12 (P<0.005) and 36 months (P<0.0001)., Conclusions: Contrary to the belief that only the recipient's immune status matters, the data indicate that pretransplant immune status of both donor and recipient influence posttransplant outcome.

Objective: To report the long-term outcomes of 1218 organs transplanted from donation after cardiac death (DCD) donors from January 1980 through December 2008., Methods: One-thousand two-hundred-eighteen organs were transplanted into 1137 recipients from 577 DCD donors. This includes 1038 kidneys (RTX), 87 livers (LTX), 72 pancreas (PTX), and 21 DCD lungs. The outcomes were compared with 3470 RTX, 1157 LTX, 903 PTX, and 409 lung transplants from donors after brain death (DBD)., Results: Both patient and graft survival is comparable between DBD and DCD transplant recipients for kidney, pancreas, and lung after 1, 3, and 10 years. Our findings reveal a significant difference for patient and graft survival of DCD livers at each of these time points. In contrast to the overall kidney transplant experience, the most recent 16-year period (n = 396 DCD and 1,937 DBD) revealed no difference in patient and graft survival, rejection rates, or surgical complications but delayed graft function was higher (44.7% vs 22.0%; P < .001). In DCD LTX, biliary complications (51% vs 33.4%; P < .01) and retransplantation for ischemic cholangiopathy (13.9% vs 0.2%; P < .01) were increased. PTX recipients had no difference in surgical complications, rejection, and hemoglobin A1c levels. Surgical complications were equivalent between DCD and DBD lung recipients., Conclusion: This series represents the largest single center experience with more than 1000 DCD transplants and given the critical demand for organs, demonstrates successful kidney, pancreas, liver, and lung allografts from DCD donors., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: We have demonstrated that immunodominant donor-specific antibody (DSA) more than 100 mean fluorescence intensity (MFI) at the time of transplant is associated with a significantly higher risk of rejection. We now present short-term outcomes of DSA-based desensitization (DSZ) strategies in patients with a negative complement-dependent cytotoxicity crossmatch., Methods: Between January 1, 2009, and January 1, 2010, live-donor kidney transplant recipients were divided into three protocols based on their immunodominant DSA MFI pretransplant (D1: 100-500, D2: 501-1000, and D3: 1001-3000). Deceased donor kidney transplant recipients were stratified into two protocols (D4: 501-1000 and D5: 1001-3000). The intensity of the conditioning treatment increased with DSA levels and included thymoglobulin induction, plasmapheresis, and intravenous immunoglobulin in the highest risk groups. We compared outcomes between desensitized patients (DSZ) and those undergoing no DSZ (or D0) during the same interval., Results: Forty-eight of 249 (23%) kidney transplants underwent DSZ (n=20, 4, 3, 4, and 17 in D1-D5 protocols, respectively). There was more retransplantation (50% vs. 18%, P<0.001) and live donor transplantation (56% vs. 30%, P<0.001) in the DSZ group. In this group, mean peak panel reactive antibody and MFI at transplant were 51% ± 7% and 960 ± 136, respectively. The incidence of antibody-mediated rejection (25% vs. 12.5%, P=0.008) and acute cellular rejection (23% vs. 14%, P=0.02) was greater in the DSZ group. However, mixed rejection (8%), graft loss (0 vs. 6), patient death (0 vs. 3), cytomegalovirus infection (15% vs. 12%), and 1-year serum creatinine (1.4 ± 0.5 and 1.4 ± 0.4 mg/dL) were similar between DSZ and no-DSZ groups. CONCLUSION.: Long-term follow-up is needed to determine the role of Luminex-based strategies in current preconditioning regimens.

Objective: This study evaluates the long-term outcomes, biliary complication rates, and risk factors for biliary complications after liver transplantation from "donation after cardiac death" (DCD) donors., Background: Recent enthusiasm toward increased use of DCD donors' livers is mitigated by high biliary complication rates. Predictive risk factors for the development of biliary complications after DCD liver transplantation remain incompletely defined., Methods: We performed a retrospective review of 1157 "donation after brain death" (DBD) and 87 DCD liver transplants performed between January 1, 1993, and December 31, 2008. Patient and graft survivals and complication rates within the first year of transplantation were compared between DBD and DCD groups. Cox proportional hazards models were used to assess the influence of potential risk factors., Results: Patient survival was significantly lower in the DCD group compared with the DBD group at 1, 5, 10, and 15 years (DCD: 84%, 68%, 54%, and 54% vs DBD: 91%, 81%, 67%, and 58%; P < 0.01). Graft survival was also significantly lower in the DCD group compared with the DBD group at 1, 5, 10, and 15 years (DCD: 69%, 56%, 43%, 43% vs DBD: 86%, 76%, 60%, 51%; P < 0.001). Rates of overall biliary complications (OBC) (DCD: 47% vs DBD: 26%; P < 0.01) and ischemic cholangiopathy (IC) (DCD: 34% vs DBD: 1%; P < 0.01) were significantly higher in the DCD group. Donor age [hazard ratio (HR): 1.04; P < 0.01] and donor age greater than 40 years (HR: 3.13; P < 0.01) were significant risk factors for the development of OBC. Multivariate analysis revealed that cold ischemic time (CIT) greater than 8 hours (HR: 2.46; P = 0.05) and donor age greater than 40 years (HR: 2.90; P < 0.01) significantly increased the risk of IC., Conclusions: Long-term patient and graft survival after DCD liver transplantation remain significantly lower but acceptable when compared with DBD liver transplantations. Donor age and CIT greater than 8 hours are the strongest predictors for the development of IC. Careful selection of younger DCD donors and minimization of CIT may limit the incidence of severe biliary complications and improve the successful utilization of DCD donors' livers.

Purpose of Review: Simultaneous pancreas-kidney (SPK) transplantation represents the only proven long-term therapeutic approach for type 1 diabetic, dialysis-dependent patients. This procedure potentially liberates these patients from dialysis and the need for exogenous insulin replacement. For the first time, data on the long-term natural history of patients receiving SPK have recently been analyzed. In this review, we discuss the outcomes and complications for patients receiving SPK in the context of the current literature., Recent Findings: In our analysis of 1000 SPKs performed at our center, we demonstrated that SPK increases patient survival compared with live-donor kidney alone or deceased donor kidney alone transplantation. The 5-year, 10-year, and 20-year patient survival for SPK recipients was 89, 80, and 58%, respectively. Enteric drainage improves quality of life, but not allograft survival, when compared with bladder drainage. After transplantation, approximately 50% of bladder-drained transplants undergo enteric conversion and late conversion after transplantation is associated with a higher complication rate. Surgical complications are higher in enteric-drained compared with bladder-drained pancreas transplants., Summary: Selecting the appropriate therapy for a type 1 diabetic recipient with renal failure continues to be a critical decision for programs offering pancreas transplantation. The principles and guidelines at our center are driven by the potential benefit of the SPK transplant needing to outweigh the increased morbidity of the surgical procedure and the use of lifelong immunosuppression. Results from long-term studies demonstrating improved patient survival suggest that the treatment of choice for an appropriate type 1 diabetic recipient is an SPK transplant.

Background: The clinical significance of pretransplant donor-specific antibodies (pre-Tx DSAs) detected by single-antigen bead flow cytometry (SAB-FC) remains unclear., Methods: To investigate the impact that pre-Tx DSAs detected by SAB-FC have on early clinical outcomes, we tested pre-Tx sera from all consecutive deceased-donor kidney transplants performed between January 2005 and July 2006 (n=237)., Results: In the study population of which 66% had a high-immunologic risk, mean fluorescence intensity (MFI) more than or equal to 100 for class I and more than or equal to 200 for class II were the lowest DSA thresholds associated with inferior antibody-mediated rejection-free graft survival (75% vs. 90%, P=0.004 and 76% vs. 87%, P=0.017, respectively). The hazard ratio for antibody-mediated rejection increased linearly with higher class II DSA from MFI 100 to 800 (1.7[0.8-3.2], P=0.1 for MFI ≥100 vs. 4.7[2.4-8.8], P<0.001 for MFI ≥ 800). Differences in graft function were only evident in patients with class II MFI more than or equal to 500 (estimated glomerular filtration rate: 47.6 vs. 54.3, P=0.02 and proteinuria: 0.6 ± 0.6 vs. 0.4 ± 0.3, P=0.03). A difference in death-censored graft survival was detected in patients with class II MFI more than or equal to 1000 (75% vs. 91.9%, P=0.055)., Conclusion: High-pre-Tx DSAs detected by SAB-FC are associated with incrementally poor graft outcomes in deceased-donor kidney transplant with high-immunologic risk.

Background: Lacto-N-fucopentaose III (LNFPIII) is a pentasaccharide containing the Lewis(x) trisaccharide that is found on schistosome eggs and in breast milk. LNFPIII conjugates suppress host immune responses and have therapeutic efficacy in mouse models of psoriasis and type 1 diabetes., Methods: We used nonvascularized neonatal ear-heart transplantation and heterotopic vascularized heart transplantation models to evaluate immunosuppressive effects of LNFPIII and subsequently analyzed the mechanism., Results: We found that administration of LNFPIII conjugates prolonged median graft survival by 80% when 1-day-old DBA/2 hearts were transplanted into ears of B6 mice. A similar graft prolongation was observed in a fully vascularized heterotopic heart transplantation model (DBA/2 into B6), No prolongation was observed with carrier protein (human serum albumin [HSA] or dextran) alone. We found increased programmed death ligand 1 (PD-L1) expression on F4/80 macrophages, CD4+ T cells, and CD11b+ CD11c+ (myeloid) dendritic cells, and increased arginase1 and Ym1 expression, typical of alternatively activated macrophages, in the draining (cervical) lymph node cells. We found accumulation of Foxp3+ regulatory T cells (Tregs) in the lymph nodes draining donor hearts, suggesting a possible role of Treg induction in graft prolongation. Anti-PD-L1 antibody treatment abrogated LNFPIII-mediated the graft survival benefit and Treg accumulation. LNFPIII-treated macrophages had increased PD-L1 expression and significantly prolonged DBA/2 allograft survival when injected intraperitoneally into B6 recipient mice., Conclusions: LNFPIII prolongs fully allogeneic graft survival in both vascularized and nonvascularized allograft transplantation models. The mechanism of graft prolongation seems to involve both alternatively activated PDL-1 macrophages and recruitment of Foxp3+ Treg cells.

Background: To determine the impact at a single center of the United Network for Organ Sharing-mandated sharing program for human leukocyte antigen (HLA)-A/-B/-DR 0-mismatched (0MM) kidneys, we analyzed the results of 264 kidney transplants from 0MM distant donors between 1993 and 2006, with a follow-up through January 31, 2007. We compared these results with that of concurrent kidneys transplanted from HLA more than 0MM local donors and with shipped more than 0MM kidneys from "payback" donors., Results: Despite a significantly longer preservation time, we found an 11% increase in 8-year graft survival (63% vs. 52%; P<0.003) of 0MM shipped versus locally procured, >0MM donor kidneys. Graft survival of 0MM shipped kidneys at 8 years was significantly better in nonsensitized (<20% panel reactive antibodies; 68% vs. 55%; P<0.0005) but not in sensitized (>or=20% panel reactive antibodies) recipients, who showed an early (2 years) but short-lived benefit. The benefit of receiving a HLA-A, -B, and -DR 0MM shipped kidney remained strong and statistically significant (0.71 relative risk of graft loss vs. local; P<0.02) when adjusted for 22 potentially confounding variables in a Cox proportional hazards analysis., Conclusions: The recent change in United Network for Organ Sharing policy restricting mandated sharing of 0MM kidneys to sensitized and pediatric recipients will give greater flexibility to the local organ procurement organization in allocating organs. However, the survival benefit to nonsensitized patients is real and long lasting and will be lost.

Background: With adoption of Model for End-Stage Liver Disease, the number of simultaneous liver-kidney transplants (SLK) has greatly increased. A recent registry study questioned the equity of allocating kidney transplants (KTx) simultaneously with liver transplantation due to poor outcomes (Locke et al., Transplantation 2008; 85: 935)., Methods: To investigate outcome of KTx in SLK, all SLK (n=36) performed at our center from January 2000 to December 2007 were reviewed and KTx outcomes compared with those of kidney transplant alone (KTA) performed during that period (n=1283). We also reviewed whether pretransplant panel reactive antibody and donor-specific antibody affected KTx outcome in SLK., Results: One- and 3-year KTx and patient survival were not different between KTA and SLK regardless of sensitization level. There were 348 (27%) KTx failures in KTA vs. 6 (17%) in SLK (NS). Overall freedom from acute cellular rejection (ACR) and antibody-mediated rejection (AMR) in SLK was 93 and 96% at 3 years, compared with 72 and 78% in KTA (P=0.0105 and P=0.0744, respectively). Sensitized KTx recipients had more ACR and AMR (32 and 38%) at 3 years compared with nonsensitized recipients (28 and 20%) (P=0.23 and 0.0001, respectively). No differences in ACR and AMR were observed when SLK was divided and level of sensitization compared (P=0.17 and 0.65, respectively)., Conclusion: SLK is a life-saving procedure with excellent patient and graft survival. AMR incidence in the KTx appears reduced in SLK compared with KTA regardless of level of preoperative panel reactive antibody. A high level of donor-specific antibody should not preclude simultaneous transplantation when clinically indicated.

The use of an antibody induction agent in kidney transplantation lowers the risk of an acute rejection episode and may improve graft outcomes. Antithymocyte globulin (ATG) is the most commonly used antibody induction agent for kidney transplantation in the United States, despite its significant side effect profile and cost compared to the interleukin-2 receptor antagonists (IL2-RA). Our review suggests the IL2-RA are safe and well tolerated, and provide equal clinical benefit to ATG at a lower cost. We propose that there is insufficient evidence to justify the use of ATG induction in kidney transplantation.

Background: Although enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce gastrointestinal (GI) side effects in kidney transplantation, a multicenter clinical trial of patients undergoing de novo renal transplantation found that efficacy failure and adverse GI event rates for EC-MPS were comparable with mycophenolate mofetil (MMF). A common strategy to mitigate mycophenolic acid-related GI adverse events includes dose manipulations such as split dosing, dose reduction, and discontinuation. Several studies have demonstrated that dose alterations with MMF are associated with poorer graft outcomes., Methods: To determine whether there was a clinically significant difference in dose alterations and outcomes with EC-MPS compared with MMF, we conducted a retrospective study comparing MMF and EC-MPS in all consecutive kidney transplants (n=1709) between 2000 and 2006., Results: Graft survival between MMF and EC-MPS patients was not different during the study period (P=0.9928). The incidence of biopsy-proven acute rejection at 2 years was higher in the MMF group (30.2% MMF vs. 21.9% EC-MPS, P=0.0004). The adjusted risk of dose reductions was significantly higher in MMF-treated patients (hazard ratio=1.703, P<0.0001). Similarly, the adjusted risk of drug discontinuation was higher in the MMF group (hazard ratio=1.507, P=0.0002). EC-MPS patients also demonstrated a trend toward a lower incidence of infections and a significantly lower incidence of fungal infections., Conclusion: EC-MPS was associated with fewer dose reductions or discontinuations, which may have translated into the observed significantly lower incidence of biopsy-proven rejection. EC-MPS has become the mycophenolic acid agent of choice at this large center.