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Major gaps remain in our understanding of antibody-mediated rejection (AMR) after kidney transplant. We examined the incidence, risk factors, response to treatment, and effects on outcomes of AMR at seven transplant programs in the long-term Deterioration of Kidney Allograft Function prospective study cohort. Among 3131 kidney recipients, there were 194 observed AMR cases (6.2%) during (mean ± SD) 4.85 ± 1.86 years of follow-up. Time to AMR was 0.97 ± 1.17 (median, 0.48) years. Risk factors for AMR included younger recipient age, human leukocyte antigen DR mismatches, panel-reactive antibody >0%, positive T- or B-cell cross-match, and delayed graft function. Compared with no AMR, the adjusted time-dependent hazard ratio for death-censored graft failure is 10.1 (95% confidence interval, 6.5-15.7) for all AMR patients, 4.0 (2.5, 9.1) for early AMR (

BACKGROUND: To gather information on long-term outcomes after living donation, the Scientific Registry of Transplant Recipients (SRTR) conducted a pilot on the feasibility of establishing a comprehensive donor candidate registry. METHODS: A convenience sample of 6 US living liver donor programs evaluated 398 consecutive donor candidates in 2018, ending with the March 12, 2020, COVID-19 emergency. RESULTS: For 333/398 (83.7%), the donor or program decided whether to donate; 166/333 (49.8%) were approved, and 167/333 (50.2%) were not or opted out. Approval rates varied by program, from 27.0% to 63.3% (median, 46%; intraquartile range, 37.3-51.1%). Of those approved, 90.4% were white, 57.2% were women, 83.1% were

Supplemental Digital Content is available in the text., Background. For liver transplant candidates on the waiting list, deciding to accept a donor organ with known or potential risk factors can be stressful and can lead to declined offers. Current education for patients and family often takes place during transplant evaluations and can be overwhelming and result in low retention and poor understanding of donor quality. Methods. In the first phase, we sought to understand provider experiences when counseling patients about donor risks and donor offers. We conducted interviews and focus groups with liver transplant providers at 1 local center and at a national clinician conference. Twenty providers participated: 15 hepatologists and 5 surgeons. The provider feedback was used to create an initial outline of content that is consistent with decision support frameworks. In a second phase, graphic design collaborators created mockups of a patient-friendly tool. We reviewed mockups with 4 transplant coordinators and 9 liver transplant candidates for feedback on clarity and utility to prepare for an organ offer. Patient responses allowed a comparison of perceived readiness to receive an offer call before and after viewing mockups. Results. We identified themes relating to the offer process, repetition and timing of education, and standardization and tailoring of content. The results indicated a gap in available education after the evaluation session, and information specific to offer decisions is needed. Patient feedback emphasized the need to review the offer process before a real offer. Conclusions. Patients and providers responded favorably to a patient tool addressing existing gaps in education while waiting for a donor offer. Additional patient, family, and provider feedback will guide the development of an interactive tool to prepare patients and families for an offer decision.

Background Identifying kidney allograft recipients who are predisposed to acute rejection (AR) could allow for optimization of clinical treatment to avoid rejection and prolong graft survival. It has been hypothesized that a part of this predisposition is caused by the inheritance of specific genetic variants. There are many publications reporting a statistically significant association between a genetic variant, usually in the form of a single-nucleotide polymorphism (SNP), and AR. However, there are additional publications reporting a lack of this association when a different cohort of recipients is analyzed for the same single-nucleotide polymorphism. Methods In this report, we attempted to validate 75 common genetic variants, which have been previously reported to be associated with AR, using a large kidney allograft recipient cohort of 2390 European Americans and 482 African Americans. Results Of those variants tested, only 1 variant, rs2910164, which alters the expression of the microRNA MIR146A, was found to exhibit a significant association within the African American cohort. Suggestive variants were found in the genes CTLA and TLR4. Conclusions Our results show that most variants previously reported to be associated with AR were not validated in our cohort. This shows the importance of validation when reporting the associations with complex clinical outcomes such as AR. Additional work will need to be done to understand the role of MIR146A in the risk of AR in kidney allograft recipients.

Background Sofosbuvir use in patients with decompensated cirrhosis may be associated with reduced liver transplant waitlist mortality and reduced need for transplant. Methods Data from the Scientific Registry of Transplant Recipients were linked with a national database of pharmacy claims. All adult patients on the liver transplant waitlist on January 1, 2014, or added to the list during 2014, with hepatitis C virus as reason for listing were identified (2009 patients). A subgroup of 1093 unique patients had consistent pharmacy claim capture and observations. We compared patients who were and were not treated with all sofosbuvir-based regimens. Results During the study period, 154 patients received sofosbuvir-based regimens. These patients had lower model for end-stage liver disease scores and significantly longer waiting times. We found a trend toward significance for more sofosbuvir-treated than untreated patients being removed from the waitlist due to improved condition (4.54% vs 3.19%, p=0.03). In a propensity score-adjusted analysis, sofosbuvir-treated patients were less likely to undergo transplant (hazard ratio 0.57, 95% confidence interval 0.37-0.89, p=0.01). Conclusion During the study period reflecting early sofosbuvir use, few liver transplant candidates received sofosbuvir. Use was associated with lower incidence of transplant and a trend toward more waitlist removals due to improved condition.

BACKGROUND AND OBJECTIVES: Dichotomization of pharmacokinetic exposure measures in exposure–response relationship studies provides results that are interpretable in clinical care. Several methods exist in the literature on how to define the cut-off values needed for the dichotomization process. Commonly, the sample median is utilized to define the dichotomizing value; however, statistical methods based on the exposure metric and its association with the outcome are argued to result in a more proper definition of the optimal cut-point. The Youden index is a recommended statistical method to define the cut-off value. The current analysis objective is to compare the dichotomization results based on the Youden index versus median methods. METHODS: Utilizing mycophenolic acid (MPA) exposure data and its related acute rejection and leukopenia outcome variables, the current study compared the MPA exposure–response relationship outcomes when MPA exposure is dichotomized via the Youden index versus median methods. Univariate logistic models were utilized to quantify the relationships between MPA exposure, including total MPA, unbound MPA, and the acyl-glucuronide metabolite of MPA, and the probabilities of acute rejection and leukopenia. RESULTS: The overall trend of the results of the logistic models demonstrated a general similarity in the inferred exposure–response associations when considering either the Youden index-based or the median-based dichotomization methods. CONCLUSION: The results demonstrated in this analysis suggest that both the Youden index and the median methods provide similar conclusions when dichotomization of a continuous variable is considered. However, confirmation of these conclusions comes from future powered studies that include a larger number of subjects.

Despite improvements in medical and surgical treatment of intestinal failure, intestine transplant continues to play an important role. In 2017, 109 intestine transplants were performed, 62 in adults and 47 in children, reflecting the changed age distribution over the past decade of candidates waitlisted for intestine and intestine-liver transplant from largely pediatric to increasing proportions of adults. In 2017, 56.0% of candidates on the intestine list at any time during the year were aged younger than 18 years, with a decrease over time in those aged younger than 6 years and an increase in those aged 6-17 years. Adults accounted for 44.0% of candidates on the list at any time during the year, with an increase since 2013 in those aged 18-34 years and a decrease in those aged 35 years or older. By age, the pretransplant mortality rate was highest for adult candidates at 7.9 per 100 waitlist-years and lowest for pediatric candidates at 3.7 per 100 waitlist-years. Patient survival varied by age and type of transplant, and was lowest for adult intestine-liver recipients (1- and 5-year survival 66.7% and 42.6%, respectively) and highest for pediatric intestine recipients (1- and 5-year survival 86.2% and 75.4%, respectively).

PURPOSE OF REVIEW Reporting provider data on quality to patients and the general public is increasingly common in healthcare. Reporting outcomes in solid organ transplantation has always been controversial and deserves careful consideration to ensure optimal results. RECENT FINDINGS As mandated by Federal law, the Scientific Registry of Transplant Recipients publishes program-specific reports on transplant candidates, recipients, donors, and transplant outcomes every 6 months. Recent changes designed to make the results more easily understood by patients and the general public have been well received by patients and controversial among providers. In particular, outcomes are now reported using a five-tier system that distinguishes program results better than the old three-tier system, in which almost all programs were reported "as expected." Metrics that reflect access to transplant are also reported, including transplant rate and survival on the waiting list. Possible measures of longer term outcomes and program rates of accepting organs for transplant are being explored. SUMMARY Providing detailed information regarding transplant program practices and outcomes in ways that patients and the general public can understand remains a major focus of the Scientific Registry of Transplant Recipients. Efforts to improve data collection and metrics reported are ongoing.

The C-statistic of the risk-adjustment model is often used to judge the accuracy of program evaluations. However, the C-statistic depends on the variability in risk for individual transplants and may be inappropriate for determining the accuracy of program evaluations. A simulation study investigated the association of the C-statistic with several metrics of program evaluation accuracy, including categorizing programs into the 5-tier system and identifying programs for regulatory review. The simulation study used data from deceased donor kidney-alone transplants for adult recipients in the program-specific reports released January 2018. A range of C-statistics was generated by changing the variability in risk for individual transplants. The C-statistic had no association with any metric of program evaluation accuracy. Instead, the number of expected events at a program was the most important factor. For example, Spearman’s rho, which is the correlation of ranks, was −0.27 and −0.72 between the true program-specific hazard ratios and assigned tiers for programs with, respectively, less than 3 and more than 10 expected events. Presence of unadjusted risk factors did not modify the associations, although the accuracy of program evaluations was systematically lower. Therefore, the C-statistic provides no information on the accuracy of program evaluations.

In 2017, 3273 heart transplants were performed in the United States. New listings continued to increase, and 3769 new adults were listed for heart transplant in 2017. Over the past decade, posttransplant mortality has declined. The number of new pediatric listings increased over the past decade, as did the number of pediatric heart transplants, although some fluctuation has occurred more recently. New listings for pediatric heart transplants increased from 481 in 2007 to 623 in 2017. The number of pediatric heart transplants performed each year increased from 330 in 2007 to 432 in 2017, slightly fewer than in 2016. Short-term and long-term mortality improved. Among pediatric patients who underwent transplant between 2015-2016, 4.8% had died by 6 months and 6.2% by 1 year.

The Scientific Registry of Transplant Recipients (SRTR) is mandated by the National Organ Transplant Act, the Final Rule, and the SRTR contract with the Health Resources and Services Administration to report program-specific information on the performance of transplant programs. Following a consensus conference in 2012, SRTR developed a new version of the public website to improve public reporting of often complex metrics, including changing from a 3-tier to a 5-tier summary metric for first-year posttransplant survival. After its release in December 2016, the new presentation was moved to a “beta” website to allow collection of additional feedback. SRTR made further improvements and released a new beta website in May 2018. In response to feedback, SRTR added 5-tier summaries for standardized waitlist mortality and deceased donor transplant rate ratios, along with an indicator of which metric most affects survival after listing. Presentation of results was made more understandable with input from patients and families from surveys and focus groups. Room for improvement remains, including continuing to make the data more useful to patients, deciding what additional data elements should be collected to improve risk adjustment, and developing new metrics that better reflect outcomes most relevant to patients.

SRTR uses data collected by OPTN to calculate metrics such as donation rate, organ yield, and rate of organs recovered for transplant but not transplanted. In 2017, 1,085,646 death and imminent death referrals were made to organ procurement organizations, of which 22,265 met the definition of eligible (11,673) or imminent neurological (10,592) deaths per OPTN policy. There were 10,286 deceased donors, and this number has been increasing since 2010. The number of organs authorized for recovery has also continued to increase since 2010. The recent increase may be in part due to the rising number of deaths of young individuals due to the opioid epidemic. In 2017, 4813 organs were discarded, including 3542 kidneys, 309 pancreata, 742 livers, 4 intestines, 33 hearts, and 272 lungs. These numbers suggest a need to reduce the number of organs discarded.

An extreme phenotype sampling (EPS) model with targeted next-generation sequencing (NGS) identified genetic variants associated with tacrolimus (Tac) metabolism in subjects from the Deterioration of Kidney Allograft Function (DeKAF) Genomics cohort which included 1,442 European Americans (EA) and 345 African Americans (AA). This study included 48 subjects separated into 4 groups of 12 (AA high, AA low, EA high, EA low). Groups were selected by the extreme phenotype of dose-normalized Tac trough concentrations after adjusting for common genetic variants and clinical factors. NGS spanned > 3 Mb of 28 genes and identified 18,661 genetic variants (3961 previously unknown). A group of 125 deleterious variants, by SIFT analysis, were associated with Tac troughs in EAs (burden test, p = 0.008), CYB5R2 was associated with Tac troughs in AAs (SKAT, p = 0.00079). In CYB5R2, rs61733057 (increased allele frequency in AAs) was predicted to disrupt protein function by SIFT and PolyPhen2 analysis. The variants merit further validation.

The Final Rule mandates that organ allocation not be based on the transplant candidate's place of residence or listing, except as required by sound medical judgment and best use of donated organs, to avoid wasting organs and futile transplants, and to promote access and efficiency. Current Organ Procurement and Transplantation Network (OPTN) policies use donation service areas and OPTN regions to distribute and allocate organs for transplant. These policies have recently been called into question as not meeting the requirements of the Final Rule. Therefore, we propose using borderless allocation scores that combine medical priority scores with geographic feasibility scores. Medical priority scores are currently used in OPTN allocation policy, for example, the model for end-stage liver disease and the lung allocation score. Geographic feasibility scores can be developed to account for the effects of ischemia due to travel times, donor characteristics that modify the feasibility of traveling due to organ outcomes, and the costs of shipping organs over long distances. A borderless distribution and allocation system could address the goals of equity and utility, while fulfilling the mandates of the Final Rule and providing optimal use of a scare resource.

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

Despite the ongoing severe shortage of available kidney grafts relative to candidates in need, data from 2019 reveal some promising trends. After remaining relatively stagnant for many years, the number of kidney transplants has increased each year since 2015, reaching the highest annual count to date of 24,273 in 2019. The number of patients waiting for a kidney transplant in the United States was relatively stable, despite an increase in the number of new candidates added in 2019 and a decrease in patients removed from the waiting list owing to death or deteriorating medical condition. However, these encouraging trends are tempered by ongoing challenges. Nationwide, only a quarter of waitlisted patients receive a deceased-donor kidney transplant within 5 years, and this proportion varies dramatically by donation service area, from 15.5% to 67.8%. The non-utilization (discard) rate of recovered organs remains at 20.1%, despite adramatic decline in the discard of organs from hepatitis C-positive donors. Non-utilization rates remain particularly high for Kidney Donor Profile Index ≥85% kidneys and kidneys from which a biopsy specimen was obtained. While the number of living-donor transplants increased again in 2019, only a small proportion of the waiting list receives living-donor transplants each year, and racial disparities in living-donor transplant access persist. As both graft and patient survival continue to improve incrementally, the total number of living kidney transplant recipients with a functioning graft is anticipated to exceed 250,000 in the next 1-2 years. Over the past decade, the total number of pediatric kidney transplants performed has remained stable. Despite numerous efforts, living donor kidney transplant remains low among pediatric recipients with continued racial disparities among recipients. Congenital anomalies of the kidney and urinary tract remain the leading cause of kidney disease. While most deceased donor recipients receive a kidney from a donor with KDPI less than 35%, the majority of pediatric recipients had four or more HLA mismatches. Graft survival continues to improve with superior outcomes for living donor recipients.

This year was notable for changes to exception points determined by the geographic median allocation Model for End-Stage Liver Disease (MELD) and implementation of the National Liver Review Board, which took place on May 14, 2019. The national acuity circle liver distribution policy was also implemented but reverted to donor service area- and region-based boundaries after 1 week. In 2019, growth continued in the number of new waiting list registrations (12,767) and transplants performed (8,896), including living-donor transplants (524). Compared with 2018, living-donor liver transplants increased 31%. Women continued to have a lower deceased-donor transplant rate and a higher pretransplant mortality rate than men. The median waiting time for candidates with a MELD of 15-34 decreased, while the number of transplants performed for patients with exception points decreased. These changes may have been related to the policy changes that took effect in May 2019, which increased waiting list priority for candidates without exception status. Hepatitis C continued to decline as an indication for liver transplant, as the proportion of liver transplant recipients with alcohol-related liver disease and clinical profiles consistent with non-alcoholic steatohepatitis increased. Graft and patient survival have improved despite changing recipient demographics including older age, higher MELD, and higher prevalence of obesity and diabetes.

Patients in the US in need of a life-saving organ transplant must complete a long process of medical decisions, and a first step is to identify a transplant center to complete an evaluation. This study describes a patient-centered process of testing and refinement of a new website (www.transplantcentersearch.org) that was developed to provide data to patients who are seeking a transplant center. Mixed methods, including online surveys and structured usability testing, were conducted to inform changes in an iterative process. Survey data from 684 participants indicated the effects of different icon styles on user decisions. Qualitative feedback from 38 usability testing participants informed improvements to the website interface. The mixed methods approach was feasible and well suited to the need to address multiple development steps of a patient-facing tool. The combined methods allowed for large survey sample sizes and also allowed interaction with a functioning website and in-depth qualitative discussions. The approach is applicable for a broad range of target user groups who are faced with challenging decisions and a need for information tailored to individual users. The survey and usability testing concluded with a functioning website that is positively received by users and meets the objective to support patient decisions when seeking an organ transplant.

BACKGROUND: The Scientific Registry of Transplant Recipients provides transplant program-specific information, but it is unclear what patients and stakeholders need to know. Acceptance criteria for the candidate waitlist and donor organs vary by program and region, but there is no means to search for programs by the clinical profiles of recipients and donors. METHODS: We examined variability in program-specific characteristics that could influence access to transplantation. We also conducted three interviews and three focus groups with heart transplant candidates and recipients. Participants evaluated prototypes of a patient-specific search tool and its capacity to identify programs tailored to specific patient needs. Patient experiences and feedback influenced the development of tools. RESULTS: The distribution of recipient and donor characteristics influenced access to transplantation, as age and body mass index varied across programs (all with p < .01). Several themes emerged related to decision-making and the perceived usability of the patient-specific search. Perceptions of the prototypes varied, but were positive overall and support making the patient-specific search publicly available. Participants revealed barriers to evaluating transplant programs and suggest that patient-specific search results may optimize the process. CONCLUSIONS: The patient-specific tool (http://transplantcentersearch.org/) is valued by heart transplant patients and is important to maximizing access to transplant.

Genetic variation in the CYP3A4 and CYP3A5 (CYP3A4/5) genes, which encode the key enzymes in tacrolimus metabolism, is associated with tacrolimus clearance and dose requirements. Tacrolimus has a narrow therapeutic index with high intra- and intersubject variability, in part because of genetic variation. High tacrolimus clearance and low trough concentration are associated with a greater risk for rejection, whereas high troughs are associated with calcineurin-induced toxicity. The objective of this study was to develop a model of tacrolimus clearance with a dosing equation accounting for genotypes and clinical factors in adult kidney transplant recipients of European ancestry that could preemptively guide dosing. Recipients receiving immediate-release tacrolimus for maintenance immunosuppression from 2 multicenter studies were included. Participants in the GEN03 study were used for tacrolimus model development (n = 608 recipients) and was validated by prediction performance in the DeKAF Genomics study (n = 1361 recipients). Nonlinear mixed-effects modeling was used to develop the apparent oral tacrolimus clearance (CL/F) model. CYP3A4/5 genotypes and clinical covariates were tested for their influence on CL/F. The predictive performance of the model was determined by assessing the bias (median prediction error [ME] and median percentage error [MPE]) and the precision (root median squared error [RMSE]) of the model. CYP3A5*3, CYP3A4*22, corticosteroids, calcium channel blocker and antiviral drug use, age, and diabetes significantly contributed to the interindividual variability of oral tacrolimus apparent clearance. The bias (ME, MPE) and precision (RMSE) of the final model was good, 0.49 ng/mL, 6.5%, and 3.09 ng/mL, respectively. Prospective testing of this equation is warranted.

What is known and objective Pharmacogenomic biomarkers are now used in many clinical care settings and represent one of the successes of precision medicine. Genetic variants are associated with pharmacokinetic and pharmacodynamic changes leading to medication adverse effects and changes in clinical response. Actionable pharmacogenomic variants are common in transplant recipients and have implications for medications used in transplant, but yet are not broadly incorporated into practice. Methods From the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group guidelines, and PharmGKB databases, 12 pharmacogenomic genes with 30 variants were selected and used to create diplotypes and actionable pharmacogenomic phenotypes. A total of 853 kidney allograft recipients who had genomic information available from a genome-wide association study were included. Results Each recipient had at least one actionable pharmacogenomic diplotype/phenotype, whereas the majority (58%) had three or four actionable diplotypes/phenotypes and 17.4% had five or more among the 12 genes. The participants carried actionable diplotypes/phenotypes for multiple medications, including tacrolimus, azathioprine, clopidogrel, warfarin, simvastatin, voriconazole, antidepressants and proton-pump inhibitors. What is new and conclusion Pharmacogenomic variants are common in transplant recipients, and transplant recipients receive medications that have actionable variants. Clinical trial Genomics of Transplantation, clinicaltrials.gov (NCT01714440).

Background. Patients face obstacles in finding a transplant program that meets their healthcare needs. Acceptance criteria and waiting times vary by region and program. The Scientific Registry of Transplant Recipients provides program-specific information, but it is unclear what patients and referring physicians need to know. Methods. We examined variability in program-specific characteristics that could influence access to transplantation. We also conducted 20 interviews and 16 focus groups with transplant candidates, recipients, and their family members. Participants were shown prototypes of a patient-specific search tool and evaluated its capacity to identify programs tailored to the needs of individual patients. Results. The distribution of recipient and donor characteristics that may impact access to transplantation, such as recipients on Medicaid, varied across programs (all with P < 0.01). Several themes emerged related to impressions of access to transplantation and the usability of patient-specific search functions. Perceptions of the prototypes and results varied, but were positive overall and support providing an individualized search of program level data. Participants revealed significant barriers to identifying and evaluating transplant programs and suggest that patient-specific search results reduce the anxiety associated with selecting a program. Conclusions. Providing patient-specific tools is valued by patients and important to maximizing access to transplant.

Donor-recipient (D-R) differences at human leukocyte antigen (HLA) loci are currently incorporated into organ sharing, allocation and immunosuppression decisions. However, while acute rejection episodes have substantially diminished, progressive histologic damage occurs in allografts and improved long-term survival remains an unrealized goal among kidney recipients. Here we tested the hypothesis that non-HLA dependent, genome-wide D-R genetic differences could contribute to unchecked alloimmunity with histologic and functional consequences, culminating in long-term allograft failure. Genome-wide single nucleotide polymorphism (SNP) array data, excluding the HLA region, was utilized from 385 transplants to study the role of D-R differences upon serial histology and allograft survival. ADMIXTURE analysis was performed to quantitatively estimate ancestry in each D-R pair and PLINK was used to estimate the proportion of genome-shared identity-by-descent (pIBD) between D-R pairs. Subsequently, quantitative measures of recipient ancestry based on non-HLA SNPs was associated with death-censored allograft survival in adjusted Cox models. In D-R pairs of similar ancestry, pIBD was significantly associated with allograft survival independent of HLA mismatches in 224 transplants. Surprisingly, pIBD and recipient ancestry were not associated with clinical or subclinical rejection at any time post-transplant. Significantly, in multivariable analysis, pIBD inversely correlated with vascular intimal fibrosis in 160 biopsies obtained less than one year which in turn was significantly associated with allograft survival. Thus, our novel data show that non-HLA D-R differences associate with early vascular intimal fibrosis and allograft survival.

This population-based cohort study examines associations of voriconazole and other antifungal medications with risk of keratinocyte carcinomas in recipients of lung transplants., Key Points Question What is the association between voriconazole, an antifungal used to treat aspergillosis infections, and the risk of keratinocyte carcinomas among recipients of lung transplants? Findings In a population-based cohort study of 9599 non-Hispanic white recipients of 9793 lung transplants in the United States (2007-2016) with linkage to pharmacy claims, increasing cumulative voriconazole exposure was associated with an increased risk of cutaneous squamous cell carcinoma. Meaning These findings suggest that physicians caring for lung transplant recipients at high risk for aggressive keratinocyte carcinomas should limit voriconazole exposure when possible and encourage skin protection behaviors and more frequent cancer screenings., Importance The antifungal medication voriconazole is used to prevent and treat aspergillosis, a major cause of mortality among recipients of lung transplants (hereinafter referred to as lung recipients). Small studies suggest that voriconazole increases risk of cutaneous squamous cell carcinoma (SCC). Objective To examine associations of voriconazole and other antifungal medications with risk of keratinocyte carcinomas (SCC and cutaneous basal cell carcinoma [BCC]) in lung recipients. Design, Setting, and Participants This population-based cohort study included non-Hispanic white patients (n = 9599) who underwent lung transplant in the United States from January 1, 2007, to December 31, 2016, identified through the national Scientific Registry of Transplant Recipients with data linkable to pharmacy claims. Data were analyzed from March 1, 2018, to February 13, 2019. Exposures Antifungal medication use, including voriconazole, itraconazole, posaconazole, and other antifungals, was ascertained from pharmacy claims and treated as a time-varying exposure (assessed every 30 days). Cumulative antifungal exposure was calculated as the total number of exposed months. Main Outcomes and Measures Primary outcomes were the first SCC or BCC reported to the transplant registry by transplant centers. Follow-up began at transplant and ended at SCC or BCC diagnosis, transplant failure or retransplant, death, loss to follow-up, or December 31, 2016. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (AHRs) for each antifungal medication. Results Among the 9793 lung transplants in 9599 recipients included in the analysis, median age at transplant was 59 (interquartile range [IQR], 48-65) years, 5824 (59.5%) were male, and 5721 (58.4%) reported ever smoking. During a median follow-up of 3.0 (IQR, 1.4-5.0) years after transplant, 1031 SCCs (incidence, 322 per 10 000 person-years) and 347 BCCs (incidence, 101 per 10 000 person-years) were reported. Compared with lung recipients with no observed voriconazole use, those with 1 to 3 months of voriconazole use experienced increased AHR for SCC of 1.09 (95% CI, 0.90-1.31); 4 to 7 months, 1.42 (95% CI, 1.16-1.73); 8 to 15 months, 2.04 (95% CI, 1.67-2.50); and more than 15 months, 3.05 (95% CI, 2.37-3.91). Ever itraconazole exposure was associated with increased SCC risk (AHR, 1.20; 95% CI, 1.00-1.45). For BCC, risk was not associated with voriconazole use but was increased with itraconazole use (AHR, 1.74; 95% CI, 1.27-2.37) or posaconazole use (AHR, 1.55; 95% CI, 1.00-2.41). Conclusions and Relevance In this study, voriconazole use was associated with increased SCC risk among lung recipients, especially after prolonged exposure. Further research evaluating the risk-benefit ratio of shorter courses or alternative medications in transplant recipients at high risk for SCC should be considered.

Background Candidates for repeat kidney transplant (KT) have increased. While graft and patient survival are inferior to primary KT, second and third KTs improve patient survival over dialysis. Little is known about the outcomes after fourth KTs. Methods We retrospectively compared characteristics of third and fourth KTs in the SRTR. Factors associated with graft survival in third vs fourth KT and patient survival of fourth KT vs patients waitlisted for a 4th KT were assessed by Cox regression and multivariable linear regression analysis. Results There were 3055 third- and fourth-time KTs performed in the United States. Fourth-time graft survival was not significantly different from third-time transplants (HR 1.06, P = .653). Patients who received a fourth KT have a significant survival advantage compared with patients who remained on the waitlist for a fourth KT (HR = 0.53, P = .006). Conclusions Graft and patient survival of fourth KTs are comparable to third KTs, but inferior to first and second KTs in terms of graft and patient survival. Recipients of fourth KT have had an increased life expectancy compared with patients waitlisted for a fourth KT.

The Organ Procurement and Transplantation Network's Membership and Professional Standards Committee implemented an operational rule on March 1, 2017, intended to increase the number of kidneys transplanted from donors with kidney donor profile index (KDPI) ≥ 85% into recipients with poor estimated posttransplant survival (≥ 80%). Using data from the Scientific Registry of Transplant Recipients, ordinal and logistic regressions estimated, respectively, differences in kidney yield (number of transplanted kidneys per recovered donor) and offer acceptance practices before and after implementation. We included donors recovered January 1, 2016-February 28, 2018. The odds of higher kidney yield for donors with KDPI ≥ 85% were 27% higher after implementation (odds ratio, 1.06 1.271.53 ), but odds were also 20% higher for donors with KDPI

Two renal-risk variants in the apolipoprotein L1 gene (APOL1) in African American (AA) deceased donors (DD) are associated with shorter renal allograft survival after transplantation. To identify additional genes contributing to allograft survival, a genome-wide association study was performed in 532 AA DDs. Phenotypic data were obtained from the Scientific Registry of Transplant Recipients. Association and single-nucleotide polymorphism (SNP)-by-APOL1 interaction tests were conducted using death-censored renal allograft survival accounting for relevant covariates. Replication and inverse-variance-weighted meta-analysis were performed using data from 250 AA DD in the Genomics of Transplantation study. Accounting for APOL1, multiple SNPs near the Nudix Hydrolase 7 gene (NUDT7) showed strong independent effects (P = 1.6 × 10(−8)−2.2 × 10(−8)). Several SNPs in the Translocation protein SEC63 homolog (SEC63; P = 2 × 10(−9)-3.7 × 10(−8)) and plasmacytoma variant translocation 1 (PVT1) genes (P = 4.0 × 10(−8)-7 × 10(−8)) modified the effect of APOL1 on allograft survival. SEC63 is expressed in human renal tubule cells and glomeruli, and PVT1 is associated with diabetic kidney disease. Overall, associations were detected for 41 SNPs (P = 2 × 10(−9)-5 × 10(−8)) contributing independently or interacting with APOL1 to impact renal allograft survival after transplantation from AA DD. Given the small sample size of the discovery and replication sets, independent validations and functional genomic efforts are needed to validate these results.

Data on adult liver transplants performed in the US in 2018 are notable for (1) continued growth in numbers of new waitlist registrants (11,844) and transplants performed (8250); (2) continued increase in the transplant rate (54.5 per 100 waitlist-years); (3) a precipitous decline in waitlist registrations and transplants for hepatitis-C-related indications; (4) increases in waitlist registrants and recipients with alcoholic liver disease and with clinical profiles consistent with non-alcoholic fatty liver disease; (5) increased use of hepatitis C virus antibody-positive donor livers; and (6) continued improvement in graft survival despite changing recipient characteristics such as older age and higher rates of obesity and diabetes. Variability in transplant rates remained by candidate race, hepatocellular carcinoma status, urgency status, and geography. The volume of pediatric liver transplants was relatively unchanged. The highest rate of pre-transplant mortality persisted for children aged younger than 1 year. Children underwent transplant at higher acuity than in the past, as evidenced by higher model for end-stage liver disease/pediatric end-stage liver disease scores and listings at status 1A and 1B at transplant. Despite higher illness severity scores at transplant, pediatric graft and patient survival posttransplant have improved over time.

Despite the ongoing severe mismatch between organ need and supply, data from 2018 revealed some promising trends. For the fourth year in a row, the number of patients waiting for a kidney transplant in the US declined and numbers of both deceased and living donor kidney transplants increased. These encouraging trends are tempered by ongoing challenges, such as a large proportion of listed patients with dialysis time longer than 5 years. The proportion of candidates aged 65 years or older continued to rise, and the proportion undergoing transplant within 5 years of listing continued to vary dramatically nationwide, from 10% to nearly 80% across donation service areas. Increasing trends in the recovery of organs from hepatitis C positive donors and donors with anoxic brain injury warrant ongoing monitoring, as does the ongoing discard of nearly 20% of recovered organs. While the number of living donor transplants increased, racial disparities persisted in the proportion of living versus deceased donors. Strikingly, the total number of kidney transplant recipients alive with a functioning graft is on track to pass 250,000 in the next 1-2 years. The total number of pediatric kidney transplants remained steady at 756 in 2018. Deeply concerning to the pediatric community is the persistently low level of living donor kidney transplants, representing only 36.2% in 2018.

The new adult heart allocation policy was approved in 2016 and implemented in October 2018, so its effect was not yet evident in 2018 data. However, the more granular data being collected are anticipated to allow for improved analyses. In 2018, new listings continued to increase; 3883 new adult and 685 new pediatric candidates were added. In 2018, 3440 heart transplants were performed, an increase of 167 over 2017; 473 transplants occurred in pediatric recipients and 2967 in adult recipients. Short-term and long-term posttransplant mortality improved. Overall 1-year survival for adults who underwent heart transplant in 2011-2013 was 90.3%, 3-year survival was 84.7%, and 5-year survival was 79.6%. Mortality rates for pediatric recipients were 4.5% at 6 months and in 5.9% at 1 year posttransplant, 12.5% at 3 years for transplants in 2014-2015, 14.8% at 5 years for transplants in 2012-2013, and 29.8% at 10 years for transplants performed in 2008-2009.

SRTR uses data collected by OPTN to calculate metrics such as donation rate, organ yield, and rate of organs recovered for transplant but not transplanted. In 2018, there were 10,721 deceased donors, and this number has been increasing since 2010. The number of deceased donor transplants increased to 29,676 in 2018 from 28,582 in 2017, and this number has been increasing since 2012. The recent increase may be due in part to the rising number of deaths of young people due to the opioid epidemic. In 2018, 4994 organs were discarded, slightly more than 4813 in 2017. In 2018, 3755 kidneys, 278 pancreata, 707 livers, 3 intestines, 23 hearts, and 317 lungs were discarded. These numbers suggest an opportunity to increase numbers of transplants by reducing discards.

Cytochrome P450 3A5 (CYP3A5) and cytochrome P450 3A4 (CYP3A4) are the predominate enzymes responsible for tacrolimus metabolism. The presence of CYP3A4 and CYP3A5 genetic variants significantly affects tacrolimus clearance and dose requirements. CYP3A5*3 is a loss-of-function variant resulting in no CYP3A5 enzyme production. CYP3A4*22 is a variant that reduces production of functional CYP3A4 protein. Caucasians commonly carry these variant alleles but are very rarely homozygous for both CYP3A5*3 and CYP3A4*22. This report describes four kidney transplant recipients who carry a rare genotype combination (CYP3A5*3/*3 and CYP3A4*22/*22). These patients were identified from a larger cohort of Caucasian kidney transplant recipients (n=1366). To understand the significance of this genotype combination on tacrolimus troughs and doses, we compared these patients to recipients without this combination. Patients homozygous for both variants are at risk for profound reductions in metabolism of CYP3A substrates. A 342% and a 90.6% increase in the median dose-normalized trough was observed, when the CYP3A5*3/*3 and CYP3A4*22/*22 genotype combination was compared to the CYP3A5*1/*1 and CYP3A4*1/*1 genotype combination and the CYP3A5*3/*3 and CYP3A4*1/*1 genotype combination, respectively. These four individuals only required on average 2.5 mg/day of tacrolimus. Knowledge of these genotypes would be useful in selecting appropriate tacrolimus doses to avoid overexposure.

The Scientific Registry of Transplant Recipients (SRTR) is considering more prominent reporting of program-specific adjusted transplant rate ratios (TRRs). To enable more useful reporting of TRRs, SRTR updated the transplant rate models to adjust explicitly for components of allocation priority. We evaluated potential associations between TRRs and components of allocation priority that could indicate programs' ability to manipulate TRRs by denying or delaying access to low-priority candidates. Despite a strong association with unadjusted TRRs, we found no candidate-level association between the components of allocation priority and adjusted TRRs. We found a strong program-level association between median laboratory Model for End-stage Liver Disease (MELD) score at listing and program-specific adjusted TRRs (r = .37; P

Background Nephronophthisis (NPH) is the most prevalent genetic cause for ESRD in children. However, little is known about the prevalence of NPH in adult-onset ESRD. Homozygous full gene deletions of the NPHP1 gene encoding nephrocystin-1 are a prominent cause of NPH. We determined the prevalence of NPH in adults by assessing homozygous NPHP1 full gene deletions in adult-onset ESRD.Methods Adult renal transplant recipients from five cohorts of the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN) underwent single-nucleotide polymorphism genotyping. After quality control, we determined autosomal copy number variants (such as deletions) on the basis of median log2 ratios and B-allele frequency patterns. The findings were independently validated in one cohort. Patients were included in the analysis if they had adult-onset ESRD, defined as start of RRT at >= 18 years old.Results We included 5606 patients with adult-onset ESRD; 26 (0.5%) showed homozygous NPHP1 deletions. No donor controls showed homozygosity for this deletion. Median age at ESRD onset was 30 (range, 18-61) years old for patients with NPH, with 54% of patients age >= 30 years old. Notably, only three (12%) patients were phenotypically classified as having NPH, whereas most patients were defined as having CKD with unknown etiology (n=11; 42%).Conclusions Considering that other mutation types in NPHP1 or mutations in other NPH-causing genes were not analyzed, NPH is a relatively frequent monogenic cause of adult-onset ESRD. Because 88% of patients had not been clinically diagnosed with NPH, wider application of genetic testing in adult-onset ESRD may be warranted.

We developed a kidney offer acceptance decision tool to predict the probability of graft survival and patient survival for first-time kidney-alone candidates after an offer is accepted or declined, and we characterized the effect of restricting the donor pool with a maximum acceptable kidney donor profile index (KDPI). For accepted offers, Cox proportional hazards models estimated these probabilities using transplanted kidneys. For declined offers, these probabilities were estimated by considering the experience of similar candidates who declined offers and the probability that declining would lead to these outcomes. We randomly selected 5000 declined offers and estimated these probabilities 3 years post-offer had the offers been accepted or declined. Predicted outcomes for declined offers were well calibrated (< 3% error) with good predictive accuracy (AUC: graft survival, 0.69; patient survival, 0.69). Had the offers been accepted, the probabilities of graft survival and patient survival were typically higher. However, these advantages attenuated or disappeared with higher KDPI, candidate priority, and local donor supply. Donor pool restrictions were associated with worse 3-year outcomes, especially for candidates with high allocation priority. The kidney offer acceptance decision tool could inform offer acceptance by characterizing the potential risk-benefit tradeoff associated with accepting or declining an offer. This article is protected by copyright. All rights reserved.

Medicare costs vary for solid organ transplant recipients by outcome: survival with graft function, survival with graft failure, and death. Average per-person per-year reimbursement was $75 thousand for kidney recipients who survived the first year posttransplant with a functioning graft, $171 thousand for those who required a return to dialysis or retransplant, and $350 thousand for those who died with function. For pancreas recipients: $105 thousand for those who survived the first year with a functioning graft, $120 thousand for those who survived pancreas failure, and $443 thousand for those who died with function. For liver recipients: $154 thousand for those who survived with a functioning graft, $388 thousand for those who required retransplant, and $740 thousand who died with function. For intestine recipients: $301 thousand for those who survived with a functioning graft and $1 million for those who died with function. For heart recipients: $272 thousand for those who survived with a functioning graft and $1.2 million for those who died with function. For lung recipients: $196 thousand for those who survived with a functioning graft, $642 thousand for those who required retransplant, and $761 thousand for those who died with function.

Data on adult liver transplants performed in the US in 2016 are no-table for (1) the largest total number of transplants performed (7841); (2) the shortest median waiting time in recent history (11.3 months); (3) continued reduction in waitlist registrations and transplants for hepatitis C-related indications; (4) increasing numbers of patients whose clinical profiles are consistent with non-alcoholic fatty liver disease; and (5) equilibration of transplant rates in patients with and without hepatocellular carcinoma. Despite the increase in the number of available organs, waitlist mortality remained an important concern. Graft survival rates continued to improve. In 2016, 723 new active candidates were added to the pediatric liver transplant waiting list, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) was stable, 408 active and 169 inactive. The number of pediatric living donor liver transplants decreased from a peak of 79 in 2015 to 62 in 2016, with most from donors closely related to the recipients. Graft survival continued to improve over the past decade among recipients of deceased donor and living donor livers.

In 2016, 2692 candidates aged 12 years or older were added to the lung transplant waiting list; 2345 transplants were performed, the largest number of any prior year. The median waiting time for listed candidates in 2016 was 2.5 months, and waiting times were shortest for group D candidates. The transplant rate increased to 191.9 transplants per 100 waitlist years in 2016, with a slight decrease in waitlist mortality to 15.1 deaths per 100 waitlist years. Short-term survival continued to improve, with a 6-month death rate of 6.6% and a 1-year death rate of 10.8% among recipients in 2015 compared with 8.0% and 13.3%, respectively, among recipients in 2014. Long-term survival rates remained unchanged; 55.6% of recipients were alive at 5 years. In 2016, 23 new candidates aged 0-11 years were added to the waiting list and 16 lung transplants were performed. Incidence of posttransplant mortality for lung transplant recipients aged 0-11 years who underwent transplant in 2014-2015 was 13.8% at 6 months and 19.6% at 1 year. Changes in waitlist and transplant demographic features continued to evolve following implementation of the revised lung allocation score in 2015. Some early trends that may be attributable to the revised LAS are shorter waiting times, stabilization of the number of group D candidates listed for transplant, and convergence of LAS with lower prevalence of extremely high scores.

SRTR uses data collected by OPTN to calculate metrics such as donation rate, organ yield, and rate of organs recovered for transplant but not transplanted. In 2016, 1,072,717 death and imminent death referrals were made to organ procurement organizations, of which 23,433 met the definition of eligible (10,717) or imminent (12,716) deaths per OPTN policy. There were 9971 deceased donors, and this number has been increasing since 2010. The number of organs authorized for recovery has also continued to increase since 2010. In 2016, 4859 organs were discarded, including 3631 kidneys, 317 pancreata, 739 livers, 8 intestines, 31 hearts, and 211 lungs. These numbers suggest a need to reduce the number of organs discarded.

Despite improvements in medical and surgical treatment of intestinal failure, intestine transplant continues to play an important role. In 2016, a total of 147 intestine transplants were performed, 80 intestine-without-liver and 67 intestine-liver. Over the past decade, the age distribution of candidates waitlisted for intestine and intestine-liver transplant shifted from primarily pediatric to increasing proportions of adults. In 2016, 58.2% of candidates on the intestine list at any time during the year were aged younger than 18 years, with a decrease over time in those aged younger than 6 years and an increase in those aged 6-17 years. Adults accounted for 41.9% of candidates on the list at any time during the year, with a stable proportion of those aged 18-34 years and a decrease in those aged 35 years or older. By age, pretransplant mortality rate was highest for adult candidates at 11.7 per 100 waitlist years and lowest for children aged younger than 6 years at 2.2 per 100 waitlist years. For intestine transplants with or without a liver in 2009-2011, 1- and 5-year graft survival was 72.0% and 54.1%, respectively, for recipients aged younger than 18 years, and 70.5% and 44.1%, respectively, for recipients aged 18 years or older.

Objective To better inform health care consumers by better identifying differences in transplant program performance. Data Source Adult kidney transplants performed in the United States, January 1, 2012–June 30, 2014. Study Design In December 2016, the Scientific Registry of Transplant Recipients instituted a five-tier system for reporting transplant program performance. We compare the differentiation of program performance and the simulated misclassification rate of the five-tier system with the previous three-tier system based on the 95 percent credible interval. Data Collection Scientific Registry of Transplant Recipients database. Principal Findings The five-tier system improved differentiation and maintained a low misclassification rate of less than 22 percent for programs differing by two tiers. Conclusion The five-tier system will better inform health care consumers of transplant program performance.

Renal allografts from deceased African American donors with two apolipoprotein L1 gene (APOL1) renal-risk variants fail sooner than kidneys from donors with fewer variants. The Kidney Donor Risk Index (KDRI) was developed to evaluate organ offers by predicting allograft longevity and includes African American race as a risk factor. Substituting APOL1 genotype for race may refine the KDRI. For 622 deceased African American kidney donors, we applied a 10-fold cross-validation approach to estimate contribution of APOL1 variants to a revised KDRI. Cross-validation was repeated 10 000 times to generate distribution of effect size associated with APOL1 genotype. Average effect size was used to derive the revised KDRI weighting. Mean current-KDRI score for all donors was 1.4930 versus mean revised-KDRI score 1.2518 for 529 donors with no or one variant and 1.8527 for 93 donors with two variants. Original and revised KDRIs had comparable survival prediction errors after transplantation, but the spread in Kidney Donor Profile Index based on presence or absence of two APOL1 variants was 37 percentage points. Replacing donor race with APOL1 genotype in KDRI better defines risk associated with kidneys transplanted from deceased African American donors, substantially improves KDRI score for 85-90% of kidneys offered, and enhances the link between donor quality and recipient need.

In December 2014, a new kidney allocation system (KAS) was implemented in the United States in an attempt to improve access to transplant for historically underrepresented groups, and to incorporate longevity matching such that donor kidneys with the longest projected graft survival are given to recipients with the longest projected patient survival. The development of organ allocation policies is often guided by simulated allocation models, computer programs that simulate the arrival of donated organs and new candidates on the waiting list over a 1-year period to project outcomes under a new allocation method. We examined the early outcomes under the new KAS using quarterly data beginning in 2013, revealing whether trends were already underway before implementation. Quarterly data also serve to reveal any bolus effect, or a rapid rise or fall in the proportion of transplants in a given group due to reordering of the list, followed by tapering toward a new steady state. Post-KAS changes were notable for an increase in the proportion of transplants among younger candidates, black and Hispanic candidates, highly sensitized candidates, and those on dialysis for at least 5 years. Transplants among blood type B candidates increased slightly but these candidates remain underrepresented relative to their prevalence on the waiting list. Regional and national sharing increased under the new KAS, but transplants of kidneys with a kidney donor profile index above 85% decreased. Early graft survival appears unchanged, but given the increases in regional sharing, cold ischemia time, and transplants among highly sensitized candidates and candidates with long pretransplant dialysis time, long-term graft survival will need to monitored.

Intestine and intestine-liver transplant remains important in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2015, 196 new patients were added to the intestine transplant waiting list, with equal numbers waiting for intestine and intestine-liver transplant. Among prevalent patients on the list at the end of 2015, 63.3% were waiting for an intestine transplant and 36.7% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was notably higher for intestine-liver than for intestine transplant candidates (respectively, 19.9 vs. 2.8 deaths per 100 waitlist years in 2014-2015). By age, pretransplant mortality was highest for adult candidates, at 19.6 per 100 waitlist years, and lowest for children aged younger than 6 years, at 3.6 per 100 waitlist years. Pretransplant mortality by etiology was highest for candidates with non-congenital types of short-gut syndrome. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 70 in 2015. Intestine-liver transplants increased from a low of 44 in 2012 to 71 in 2015. Short-gut syndrome (congenital and non-congenital) was the main cause of disease leading to intestine and to intestine-liver transplant. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

As demand for kidney transplant continues to grow faster than organ availability, appropriate allocation of deceased donor kidneys is an acute priority. Increased longevity matching is central to this effort. To foster equitable and efficient utilization of deceased donor kidneys, a new kidney allocation system (KAS) was introduced in December 2014. Major achievements in the 1year after its implementation include a reduction in age-mismatch and an increase in access to transplant for historically disadvantaged candidates, such as those with very high levels of panel-reactive antibodies or long dialysis duration. However, the rate of discarded kidneys has not decreased, and an increase in A2/A2B transplants has yet to be realized. Organs are now shared more often at the regional and national levels, with some regions experiencing an increase in transplants and other a decrease. While implementation of the KAS has been associated with the attainment of key goals, the kidney transplant community must remain vigilant about potential untoward consequences, including reductions in transplant rates for specific groups such as pediatric patients. More time is required before firm conclusions about the long-term effects of the new KAS can be rendered.

The number of heart transplant candidates and transplants performed continued to rise each year. In 2015, 2819 heart transplants were performed. In addition, the number of new adult candidates on the waiting list increased 51% since 2004. The number of adult heart transplant survivors continued to increase, and in 2015, 29,172 recipients were living with heart transplants. Patient mortality following transplant has declined. The number of pediatric candidates and transplants performed also increased. New listings for pediatric heart transplants increased from 451 in 2004 to 644 in 2015. The number of pediatric heart transplants performed each year increased from 297 in 2004 to 460 in 2015. Among pediatric patients who underwent transplant in 2014, death occurred in 7.2% at 6 months and 9.6% at 1 year.

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

Every 6 months, the Scientific Registry of Transplant Recipients (SRTR) publishes evaluations of every solid organ transplant program in the United States, including evaluations of 1-year patient and graft survival. The Centers for Medicare & Medicaid Services (CMS) and the Organ Procurement and Transplantation Network (OPTN) Membership and Professional Standards Committee (MPSC) use SRTR's 1-year evaluations for regulatory review of transplant programs. Concern has been growing that the regulatory scrutiny of transplant programs with lower-than-expected outcomes is harmful, causing programs to undertake fewer high-risk transplants and leading to unnecessary organ discards. As a result, CMS raised its threshold for a "Condition-Level Deficiency" designation of observed relative to expected 1-year graft or patient survival from 1.50 to 1.85. Exceeding this threshold in the current SRTR outcomes report and in one of the four previous reports leads to scrutiny that may result in loss of Medicare funding. For its part, OPTN is reviewing a proposal from the MPSC to also change its performance criteria thresholds for program review, to review programs with "substantive clinical differences." We review the details and implications of these changes in transplant program oversight.