Allogeneic transplant procurement in the times of COVID-19: Quality report from the central European cryopreservation site.

BACKGROUND: Because of limitations of transportation imposed by the COVID-19 pandemic, current recommendation calls for cryopreservation of allogeneic stem cell transplants before patient conditioning. A single cell therapy laboratory was selected to function as the central cryopreservation hub for all European registry donor transplants intended for the Australian-Pacific region. We examined properties of these transplants to ascertain how quality is maintained. METHODS: We analyzed 100 pandemic-related allogeneic mobilized blood-derived stem cell apheresis products generated at 30 collection sites throughout Europe, shipped to and cryopreserved at our center between April and November of 2020. Products were shipped in the cool, subsequently frozen with DMSO as cryoprotectant. Irrespective of origin, all products were frozen within the prescribed shelf-life of 72 h. RESULTS: Prior to cryopreservation, viable stem cell and leukocyte count according to the collection site and our reference laboratory were highly concordant (r2 = 0.96 and 0.93, respectively) and viability was > 90% in all instances. Median nominal post-thaw recovery of viable CD34+ cells was 42%. Weakly associated with poorer CD34+ cell recovery was higher leukocyte concentration, but not time lag between apheresis or addition of cryopreservant, respectively, and start of freezing. The correlation between pre- and post-thaw CD34+ cell dose was high (r2 = 0.85), hence predictable. Neutrophil and platelet engraftment were prompt with no evidence of dose dependency within the range of administered cell doses (1.31-15.56 × 106 CD34+ cells/kg). CONCLUSIONS: General cryopreservation of allogeneic stem cell transplants is feasible. While more than half of the CD34+ cell content is lost, the remaining stem cells ensure timely engraftment.

Heterogeneous Circles for Liver Allocation.

BACKGROUND AND AIMS: In February 2020, the Organ Procurement and Transplantation Network replaced donor service area-based allocation of livers with acuity circles, a system based on three homogeneous circles around each donor hospital. This system has been criticized for neglecting to consider varying population density and proximity to coast and national borders. APPROACH AND RESULTS: Using Scientific Registry of Transplant Recipients data from July 2013 to June 2017, we designed heterogeneous circles to reduce both circle size and variation in liver supply/demand ratios across transplant centers. We weighted liver demand by Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) because higher MELD/PELD candidates are more likely to be transplanted. Transplant centers in the West had the largest circles; transplant centers in the Midwest and South had the smallest circles. Supply/demand ratios ranged from 0.471 to 0.655 livers per MELD-weighted incident candidate. Our heterogeneous circles had lower variation in supply/demand ratios than homogeneous circles of any radius between 150 and 1,000 nautical miles (nm). Homogeneous circles of 500 nm, the largest circle used in the acuity circles allocation system, had a variance in supply/demand ratios 16 times higher than our heterogeneous circles (0.0156 vs. 0.0009) and a range of supply/demand ratios 2.3 times higher than our heterogeneous circles (0.421 vs. 0.184). Our heterogeneous circles had a median (interquartile range) radius of only 326 (275-470) nm but reduced disparities in supply/demand ratios significantly by accounting for population density, national borders, and geographic variation of supply and demand. CONCLUSIONS: Large homogeneous circles create logistical burdens on transplant centers that do not need them, whereas small homogeneous circles increase geographic disparity. Using carefully designed heterogeneous circles can reduce geographic disparity in liver supply/demand ratios compared with homogeneous circles of radius ranging from 150 to 1,000 nm.

Donor Characteristics and Regional Differences in the Utilization of HCV-Positive Donors in Liver Transplantation.

Importance: Increased utilization of hepatitis C virus (HCV)-positive liver allografts for liver transplant (LT) has been endorsed as one of several ways to combat national organ shortages. However, HCV-positive donors remain poorly characterized, and Organ Procurement and Transplantation Network regional differences in the utilization of HCV-positive liver allografts are unclear. Objective: To characterize HCV-positive donors and the allografts that come from them. Design, Setting, and Participants: In this cross-sectional study, the Scientific Registry of Transplant Recipients database was queried for all donors who underwent HCV testing from June 2015 to December 2018. Clinical and allograft characteristics were evaluated, and utilization across the United States was studied. Patients with positive or negative results for HCV antibody (Ab) and HCV nucleic acid amplification testing (NAT) were included in this study. Donors utilized for living donor transplant and pediatric (age <18 years) recipients were excluded. Main Outcomes and Measures: The primary comparison was between donors who were HCV Ab positive and those who were HCV Ab negative. Regional variations in the utilization of HCV-positive and HCV-negative donors were analyzed. Results: Of 24 500 donors utilized for LT, 1887 (7.7%) were HCV Ab positive; 64.4% of HCV Ab-positive donors were HCV NAT positive. HCV Ab-positive donors were younger (median [interquartile range] age, 35 [29-46] years vs 40 [27-54] years) and had fewer comorbidities, such as diabetes (8.3% vs 12.0%) and hypertension (25.9% vs 35.2%), compared with HCV Ab-negative donors. These findings were even more pronounced in HCV Ab-positive /NAT-positive compared with HCV Ab-positive/NAT-negative donors. Organ Procurement and Transplantation Network regions 2, 3, 10, and 11 had the highest absolute utilization of HCV Ab-positive donors, accounting for 64.4% of all HCV Ab-positive donors used in the United States. Region 1 had the highest relative utilization of HCV Ab-positive donors (18.7%). The use of HCV Ab-positive donors in some regions was associated with the rate of drug overdose, but this was not always the case. Similar utilization results were found with HCV NAT-positive donors. Conclusions and Relevance: In this cross-sectional study, HCV-positive donors were younger and healthier than utilized HCV-negative donors. Significant differences exist in the utilization of HCV-positive donors across the 11 Organ Procurement and Transplantation Network regions, which is not entirely explained by organ demand or by higher availability of HCV-positive livers as per the distribution of the opioid epidemic. Initiatives to increase the use of HCV-positive donors, particularly in regions of high organ demand, should be implemented.

Living Donor Versus Deceased Donor Liver Transplantation for HCC.

INTRODUCTION: Liver transplantation is the definitive treatment modality of the patients having an end-stage liver disease with hepatocellular carcinoma. DISCUSSION: The number of living donor liver transplantations has been increased because of the deceased donor organ shortage, especially in Asian countries. CONCLUSION: Reports of different clinics about the postoperative course and tumor recurrence rates comparing living donor versus deceased donor liver transplantations, besides patient selection criteria, are reviewed along with our clinic's experiences.

What Are the Immune Obstacles to Liver Xenotransplantation Which Is Promising for Patients with Hepatocellular Carcinoma?

PURPOSE: Liver transplantation is the most important achievement in the twentieth and twenty-first century. It is the gold standard treatment for hepatocellular carcinoma. However, it provides the best results when performed under strict selection criteria. Nevertheless, organ supply is overwhelmed by the number of patients on the waiting list. There are certain strategies to expand the donor pool such as split liver transplantation, use of extended criteria donors, and living donor liver transplantation. Xenotransplantation can also be a strategy in decreasing the organ shortage. We reviewed the current status of xenotransplantation. METHODS: We evaluated the historical attempts of xenotransplantation to humans and also made a summary of the preclinical studies in the field. RESULTS: Molecular biology and genetic engineering are developing with an incredible speed. There are great achievements made in cell therapy, 3D bioprinting of the organs, and ultimately xenotransplantation. There is a vast amount of problems to be handled before evaluating the efficacy of xenotransplantation in the treatment of hepatocellular carcinoma. Major problems include antibody-mediated rejection to antigens such as galactose ⍺1-3 galactose, N- glycolylneuraminic acid, ß1,4-N-acetylgalactosaminyltransferase, lethal thrombocytopenia, and erythrocyte sequestration. Antibody mediated rejection to these specific antigens are addressed using gene editing technology including CRISPR Cas9, TALEN and other recombination methods. Although hyperacute rejection is reduced, long-term survival could not be achieved in experimental models. CONCLUSION: The future is yet to come, there are developments made in the field of genetic editing, immunosuppressive medication, and pretransplant desensitization techniques. Therefore, we believe that xenotransplantation will be in clinical practice, at least for treatment of critically ill patients.

Uncontrolled Donation After Circulatory Death: A Unique Opportunity.

Uncontrolled donation after circulatory death (uDCD) refers to donation from persons who die following an unexpected and unsuccessfully resuscitated cardiac arrest. Despite the large potential for uDCD, programs of this kind only exist in a reduced number of countries with a limited activity. Barriers to uDCD are of a logistical and ethical-legal nature, as well as arising from the lack of confidence in the results of transplants from uDCD donors. The procedure needs to be designed to reduce and limit the impact of the prolonged warm ischemia inherent to the uDCD process, and to deal with the ethical issues that this practice poses: termination of advanced cardiopulmonary resuscitation, extension of advanced cardiopulmonary resuscitation beyond futility for organ preservation, moment to approach families to discuss donation opportunities, criteria for the determination of death, or the use of normothermic regional perfusion for the in situ preservation of organs. Although the incidence of primary nonfunction and delayed graft function is higher with organs obtained from uDCD donors, overall patient and graft survival is acceptable in kidney, liver, and lung transplantation, with a proper selection and management of both donors and recipients. Normothermic regional perfusion has shown to be critical to achieve optimal outcomes in uDCD kidney and liver transplantation. However, the role of ex situ preservation with machine perfusion is still to be elucidated. uDCD is a unique opportunity to improve patient access to transplantation therapies and to offer more patients the chance to donate organs after death, if this is consistent with their wishes and values.

A Review of Donor Acute Kidney Injury and Posttransplant Outcomes.

Although over 90 000 people are on the kidney transplant waitlist in the United States, some kidneys that are viable for transplantation are discarded. Transplant surgeons are more likely to discard deceased donors with acute kidney injury (AKI) versus without AKI (30% versus 18%). AKI is defined using changes in creatinine from baseline. Transplant surgeons can use DonorNet data, including admission, peak, and terminal serum creatinine, and biopsy data when available to differentiate kidneys with AKI from those with chronic injury. Although chronic kidney disease is associated with reduced graft survival, an abundance of literature has demonstrated similar graft survival for deceased donors with AKI versus donors without AKI. Donors with AKI are more likely to undergo delayed graft function but have similar long-term outcomes as donors without AKI. The mechanism for similar graft survival is unclear. Some hypothesized mechanisms include (1) ischemic preconditioning; (2) posttransplant and host factors playing a greater role in long-term survival than donor factors; and (3) selection bias of transplanting only relatively healthy donor kidneys with AKI. Existing literature suggests transplanting more donor kidneys with stage 1 and 2 AKI, and cautious utilization of stage 3 AKI donors, may increase the pool of viable kidneys. Doing so can reduce the number of people who die on the waitlist by over 500 every year.

Generation of GGTA1-/-ß2M-/-CIITA-/- Pigs Using CRISPR/Cas9 Technology to Alleviate Xenogeneic Immune Reactions.

BACKGROUND: Xenogeneic organ transplantation has been proposed as a potential approach to fundamentally solve organ shortage problem. Xenogeneic immune responses across species is one of the major obstacles for clinic application of xeno-organ transplantation. The generation of glycoprotein galactosyltransferase α 1, 3 (GGTA1) knockout pigs has greatly contributed to the reduction of hyperacute xenograft rejection. However, severe xenograft rejection can still be induced by xenoimmune responses to the porcine major histocompatibility complex antigens swine leukocyte antigen class I and class II. METHODS: We simultaneously depleted GGTA1, ß2-microglobulin (ß2M), and major histocompatibility complex class II transactivator (CIITA) genes using clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins technology in Bamma pig fibroblast cells, which were further used to generate GGTA1ß2MCIITA triple knockout (GBC-3KO) pigs by nuclear transfer. RESULTS: The genotype of GBC-3KO pigs was confirmed by polymerase chain reaction and Sanger sequencing, and the loss of expression of α-1,3-galactose, SLA-I, and SLA-II was demonstrated by flow cytometric analysis using fluorescent-conjugated lectin from bandeiraea simplicifolia, anti-ß2-microglobulin, and swine leukocyte antigen class II DR antibodies. Furthermore, mixed lymphocyte reaction assay revealed that peripheral blood mononuclear cells from GBC-3KO pigs were significantly less effective than (WT) pig peripheral blood mononuclear cells in inducing human CD3CD4 and CD3CD8 T-cell activation and proliferation. In addition, GBC-3KO pig skin grafts showed a significantly prolonged survival in immunocompetent C57BL/6 mice, when compared with wild-type pig skin grafts. CONCLUSIONS: Taken together, these results demonstrate that elimination of GGTA1, ß2M, and CIITA genes in pigs can effectively alleviate xenogeneic immune responses and prolong pig organ survival in xenogenesis. We believe that this work will facilitate future research in xenotransplantation.

Delayed Implantation of Pumped Kidneys Decreases Renal Allograft Futility in Combined Liver-Kidney Transplantation.

BACKGROUND: Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. METHODS: A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. RESULTS: A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). CONCLUSIONS: Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.

Minimizing Risks of Liver Transplantation With Steatotic Donor Livers by Preferred Recipient Matching.

BACKGROUND: Donor livers with ≥30% macrosteatosis (steatotic livers) represent a possible expansion to the donor pool, but are frequently discarded as they are associated with an increased risk of mortality and graft loss. We hypothesized that there are certain recipient phenotypes that would tolerate donor steatosis well, and are therefore best suited to receive these grafts. METHODS: Using national registry data from the Scientific Registry of Transplant Recipients between 2006 and 2017, we compared 2048 liver transplant recipients of steatotic livers with 69 394 recipients of nonsteatotic (<30%) livers. We identified recipient factors that amplified the impact of donor steatosis on mortality and graft loss using interaction analysis, classifying recipients without these factors as preferred recipients. We compared mortality and graft loss with steatotic versus nonsteatotic livers in preferred and nonpreferred recipients using Cox regression. RESULTS: Preferred recipients of steatotic livers were determined to be first-time recipients with a model for end-stage liver disease 15-34, without primary biliary cirrhosis, and not on life support before transplant. Preferred recipients had no increased mortality risk (hazard ratio [HR]: 0.921.041.16; P = 0.5) or graft loss (HR: 0.931.031.15; P = 0.5) with steatotic versus nonsteatotic livers. Conversely, nonpreferred recipients had a 41% increased mortality risk (HR: 1.171.411.70; P < 0.001) and 39% increased risk of graft loss (HR: 1.161.391.66; P < 0.001) with steatotic versus nonsteatotic livers. CONCLUSIONS: The risks of liver transplantation with steatotic donor livers could be minimized by appropriate recipient matching.

Outcomes After Declining a Steatotic Donor Liver for Liver Transplant Candidates in the United States.

BACKGROUND: Steatotic donor livers (SDLs, ≥30% macrosteatosis on biopsy) are often declined, as they are associated with a higher risk of graft loss, even though candidates may wait an indefinite time for a subsequent organ offer. We sought to quantify outcomes for transplant candidates who declined or accepted an SDL offer. METHODS: We used Scientific Registry of Transplant Recipients offer data from 2009 to 2015 to compare outcomes of 759 candidates who accepted an SDL to 13 362 matched controls who declined and followed candidates from the date of decision (decline or accept) until death or end of study period. We used a competing risk framework to understand the natural history of candidates who declined and Cox regression to compare postdecision survival after declining versus accepting (ie, what could have happened if candidates who declined had instead accepted). RESULTS: Among those who declined an SDL, only 53.1% of candidates were subsequently transplanted, 23.8% died, and 19.4% were removed from the waitlist. Candidates who accepted had a brief perioperative risk period within the first month posttransplant (adjusted hazard ratio [aHR]: 2.493.494.89, P < 0.001), but a 62% lower mortality risk (aHR: 0.310.380.46, P < 0.001) beyond this. Although the long-term survival benefit of acceptance did not vary by candidate model for end-stage liver disease (MELD), the short-term risk period did. MELD 6-21 candidates who accepted an SDL had a 7.88-fold higher mortality risk (aHR: 4.807.8812.93, P < 0.001) in the first month posttransplant, whereas MELD 35-40 candidates had a 68% lower mortality risk (aHR: 0.110.320.90, P = 0.03). CONCLUSIONS: Appropriately selected SDLs can decrease wait time and provide substantial long-term survival benefit for liver transplant candidates.

Impact of Acuity Circles on Outcomes for Pediatric Liver Transplant Candidates.

BACKGROUND: In December 2018, United Network for Organ Sharing approved an allocation scheme based on recipients' geographic distance from a deceased donor (acuity circles [ACs]). Previous analyses suggested that ACs would reduce waitlist mortality overall, but their impact on pediatric subgroups was not considered. METHODS: We applied Scientific Registry of Transplant Recipients data from 2011 to 2016 toward the Liver Simulated Allocation Model to compare outcomes by age and illness severity for the United Network for Organ Sharing-approved AC and the existing donor service area-/region-based allocation schemes. Means from each allocation scheme were compared using matched-pairs t tests. RESULTS: During a 3-year period, AC allocation is projected to decrease waitlist deaths in infants (39 versus 55; P < 0.001), children (32 versus 50; P < 0.001), and teenagers (15 versus 25; P < 0.001). AC allocation would increase the number of transplants in infants (707 versus 560; P < 0.001), children (677 versus 547; P < 0.001), and teenagers (404 versus 248; P < 0.001). AC allocation led to decreased median pediatric end-stage liver disease/model for end-stage liver disease at transplant for infants (29 versus 30; P = 0.01), children (26 versus 29; P < 0.001), and teenagers (26 versus 31; P < 0.001). Additionally, AC allocation would lead to fewer transplants in status 1B in children (97 versus 103; P = 0.006) but not infants or teenagers. With AC allocation, 77% of pediatric donor organs would be allocated to pediatric candidates, compared to only 46% in donor service area-/region-based allocation (P < 0.001). CONCLUSIONS: AC allocation will likely address disparities for pediatric liver transplant candidates and recipients by increasing transplants and decreasing waitlist mortality. It is more consistent with federally mandated requirements for organ allocation.

Wide Variation in the Percentage of Donation After Circulatory Death Donors Across Donor Service Areas: A Potential Target for Improvement.

BACKGROUND: Substantial differences exist in the clinical characteristics of donors across the 58 donor service areas (DSAs). Organ procurement organization (OPO) performance metrics incorporate organs donated after circulatory determination of death (DCDD) donors but do not measure potential DCDD donors. METHODS: Using 2011-2016 United Network for Organ Sharing data, we examined the variability in DCDD donors/all deceased donors (%DCDD) across DSAs. We supplemented United Network for Organ Sharing data with CDC death records and OPO statistics to characterize underlying process and system factors that may correlate with donors and utilization. RESULTS: Among 52 184 deceased donors, the %DCDD varied widely across DSAs, with a median of 15.1% (interquartile range [9.3%, 20.9%]; range 0.0%-32.0%). The %DCDD had a modest positive correlation with 4 DSA factors: median match model for end-stage liver disease, proportion of white deaths out of total deaths, kidney center competition, and %DCDD livers by a local transplant center (all Spearman coefficients 0.289-0.464), and negative correlation with 1 factor: mean kidney waiting time (Spearman coefficient -0.388). Adjusting for correlated variables in linear regression explained 46.3% of the variability in %DCDD. CONCLUSIONS: Donor pool demographics, waitlist metrics, center competition, and DCDD utilization explain only a portion of the variability of DCDD donors. This requires further studies and policy changes to encourage consideration of all possible organ donors.

Deceased Donor Predictors for Pediatric Liver Allograft Utilization.

BACKGROUND: The number of pediatric deceased organ donors has recently declined, and the nonutilization of pediatric liver allografts has limited the development of liver transplantation. We determined the utilization rate of pediatric livers and identified risk factors for graft discard. METHODS: We used data from the Scientific Registry of Transplant Recipients database from January 1, 2000, to December 31, 2012. The trends of pediatric liver donors and utilization rates were analyzed. Donor risk factors that impacted the graft use of pediatric livers were measured. Logistic regression modelling was performed to evaluate graft utilization and risk factors. RESULTS: A total of 11,934 eligible pediatric liver donors were identified during this period. A total of 1191 authorized liver grafts did not recover or recovered without transplantation. Factors including pediatric donors >1 year of age (odds ratio [OR] = 2.956, 95% confidence interval [CI] 2.494-3.503, P < .001), nonhead trauma (OR = 2.243, 95% CI 1.903-2.642, P < .001), lack of heartbeat (OR = 7.534, 95% CI 5.899-9.623, P < .001), hepatitis B surface antigen positivity (OR = 4.588, 95% CI 1.021-20.625, P = .047), anti-hepatitis C virus positivity (OR = 4.691, 95% CI 1.352-16.280, P = .015), total bilirubin >1 mg/dL (OR = 1.743, 95% CI 1.469-2.068, P < .001), and blood urea nitrogen >21 mg/dL (OR = 1.941, 95% CI 1.546-2.436, P < .001) were significantly related to graft nonutilization. Steroids or diuretics administered prerecovery were significantly related to graft utilization (OR = 0.684, 95% CI 0.581-0.806, P < .001; OR = 0.744, 95% CI 0.634-0.874, P < .001; respectively). CONCLUSIONS: The pediatric liver allograft utilization rate and risk factors for nonutilization of grafts were determined.

Lessons Learned From Implementation and Management of Skin Allograft Banking Programs in Low- and Middle-Income Countries: A Systematic Review.

Wound excision and temporary coverage with a biologic dressing can improve survival for patients with large burns. Healthcare systems in low- and middle-income countries (LMICs) rarely have access to allografts, which may contribute to the limited survival of patients with large burns in these settings. Therefore, we aimed to describe the lessons learned from the implementation and maintenance of tissue banks in LMICs to guide system planning and organization. PubMed, MEDLINE, CINAHL, and World Health Organization Catalog were systematically searched with database-specific language to represent a priori terms (eg, skin, allograft, and tissue bank) and all LMICs as defined by the World Bank. Data regarding tissue banking programs were extracted and described in a narrative synthesis. The search returned 3346 records, and 33 reports from 17 countries were analyzed. Commonly reported barriers to ideal or planned implementation included high capital costs and operational costs per graft, insufficient training opportunities, opt-in donation schemes, and sociocultural stigma around donation and transplantation. Many lessons were learned from the implementation and management of tissue banks around the world. The availability of skin allografts can be improved through strategic investments in governance and regulatory structures, international cooperation initiatives, training programs, standardized protocols, and inclusive public awareness campaigns. Furthermore, capacity-building efforts that involve key stakeholders may increase rates of pledges, donations, and transplantations. Some issues were ubiquitously reported and could be addressed by current and future tissue banking programs to ensure allograft availability for patients living in countries of all income levels.

Utilization of Donor Kidneys With Acute Kidney Injury in Pediatric Kidney Transplant Recipients.

BACKGROUND: An elevated terminal creatinine is frequently used as a reason for organ refusal in pediatric kidney transplantation. There is increasing evidence that adults who receive kidneys from donors with moderate to severe acute kidney injury (AKI) have similar outcomes to recipients who receive kidneys from donors with none to mild AKI. METHODS: We used the Scientific Registry of Transplant Recipients to determine how many pediatric kidney transplant recipients developed delayed graft function (DGF) between 2000 and 2010. RESULTS: When stratified by the donor terminal creatinine, there was no significant difference in the recipient discharge creatinine or the likelihood of developing DGF. In a logistic regression model, older donor age, male donors, and a longer cold ischemia time but not donor terminal creatinine were independent predictors of DGF. There were very few graft loss events documented in this study. CONCLUSIONS: Our results are in agreement with previously published data; a high donor terminal creatinine is not significantly associated with DGF in pediatric renal transplant recipients. Additional studies investigating the risk of rejection and long-term graft function are needed before adopting the practice of accepting kidneys with moderate to severe AKI in pediatric kidney transplant recipients.

Posttransplant Outcomes for cPRA-100% Recipients Under the New Kidney Allocation System.

BACKGROUND: There is concern in the transplant community that outcomes for the most highly sensitized recipients might be poor under Kidney Allocation System (KAS) high prioritization. METHODS: To study this, we compared posttransplant outcomes of 525 pre-KAS (December 4, 2009, to December 3, 2014) calculated panel-reactive antibodies (cPRA)-100% recipients to 3026 post-KAS (December 4, 2014, to December 3, 2017) cPRA-100% recipients using SRTR data. We compared mortality and death-censored graft survival using Cox regression, acute rejection, and delayed graft function (DGF) using logistic regression, and length of stay (LOS) using negative binomial regression. RESULTS: Compared with pre-KAS recipients, post-KAS recipients were allocated kidneys with lower Kidney Donor Profile Index (median 30% versus 35%, P < 0.001) but longer cold ischemic time (CIT) (median 21.0 h versus 18.6 h, P < 0.001). Compared with pre-KAS cPRA-100% recipients, those post-KAS had higher 3-year patient survival (93.6% versus 91.4%, P = 0.04) and 3-year death-censored graft survival (93.7% versus 90.6%, P = 0.005). The incidence of DGF (29.3% versus 29.2%, P = 0.9), acute rejection (11.2% versus 11.7%, P = 0.8), and median LOS (5 d versus 5d, P = 0.2) were similar between pre-KAS and post-KAS recipients. After accounting for secular trends and adjusting for recipient characteristics, post-KAS recipients had no difference in mortality (adjusted hazard ratio [aHR]: 0.861.623.06, P = 0.1), death-censored graft failure (aHR: 0.521.001.91, P > 0.9), DGF (adjusted odds ratio [aOR]: 0.580.861.27, P = 0.4), acute rejection (aOR: 0.610.941.43, P = 0.8), and LOS (adjusted LOS ratio: 0.981.161.36, P = 0.08). CONCLUSIONS: We did not find any statistically significant worsening of outcomes for cPRA-100% recipients under KAS, although longer-term monitoring of posttransplant mortality is warranted.

A Virtual Crossmatch-based Strategy Facilitates Sharing of Deceased Donor Kidneys for Highly Sensitized Recipients.

BACKGROUND: It is estimated that 19.2% of kidneys exported for candidates with >98% calculated panel reactive antibodies are transplanted into unintended recipients, most commonly due to positive physical crossmatch (PXM). We describe the application of a virtual crossmatch (VXM) that has resulted in a very low rate of transplantation into unintended recipients. METHODS: We performed a retrospective review of kidneys imported to our center to assess the reasons driving late reallocation based on the type of pretransplant crossmatch used for the intended recipient. RESULTS: From December 2014 to October 2017, 254 kidneys were imported based on our assessment of a VXM. Of these, 215 (84.6%) were transplanted without a pretransplant PXM. The remaining 39 (15.4%) recipients required a PXM on admission using a new sample because they did not have an HLA antibody test within the preceding 3 months or because they had a recent blood transfusion. A total of 93% of the imported kidneys were transplanted into intended recipients. There were 18 late reallocations: 9 (3.5%) due to identification of a new recipient medical problem upon admission, 5 (2%) due to suboptimal organ quality on arrival, and only 4 (1.6%) due to a positive PXM or HLA antibody concern. A total of 42% of the recipients of imported kidneys had a 100% calculated panel reactive antibodies. There were no hyperacute rejections and very infrequent acute rejection in the first year suggesting no evidence for immunologic memory response. CONCLUSIONS: Seamless sharing is within reach, even when kidneys are shipped long distances for highly sensitized recipients. Late reallocations can be almost entirely avoided with a strategy that relies heavily on VXM.