US deceased kidney transplantation: Estimated GFR, donor age and KDPI association with graft survival.

BACKGROUND: Despite a significant shortage of kidneys for transplantation in the US, kidneys from older deceased donors are infrequently transplanted. This is primarily over concern of graft quality and transplant durability. METHODS: The US national transplant database (2000-2018) was assessed for deceased donor kidney transplant patient and graft survival, graft durability and stratified by donor age (<65 years>), Kidney Donor Profile Index (KDPI) and estimated glomerual filtration rate (GFR) one year post-transplantation (eGFR-1) were calculated. FINDINGS: Recipients of kidneys transplanted from deceased donors >65 years had a lower eGFR-1, (median 39 ml/min) than recipients of younger donor kidneys (median 54 ml/min). However, death-censored graft survival, stratified by eGFR-1, demonstrated similar survival, irrespective of donor age or KDPI. The durability of kidney survival decreases as the achieved eGFR-1 declines. KDPI has a poor association with eGFR-1 and lesser for graft durability. While recipients of kidneys > 65 years had a higher one year mortality than younger kidney recipients, recipients of kidneys > 65 years and an eGFR-1 <30 ml/min, had a lower survival than an untransplanted waitlist cohort (p<0.001). INTERPRETATION: The durability of kidney graft survival after transplantation was associated with the amount of kidney function gained through the transplant (eGFR-1) and the rate of graft loss (return to dialysis) was not significantly associated with donor age. 24.9% of recipients of older donor kidneys failed to achieve sufficient eGFR-1 providing a transplant survival benefit. While there is significant benefit from transplanting older kidneys, better decision-making tools are required to avoid transplanting kidneys that provide insufficient renal function. FUNDING: None.

Navigating the COVID-19 pandemic: Initial impacts and responses of the Organ Procurement and Transplantation Network in the United States.

COVID-19 has been sweeping the globe, hitting the United States particularly hard with a state of emergency declared on March 13, 2020. Transplant hospitals have taken various precautions to protect patients from potential exposure. OPTN donor, candidate, and transplant data were analyzed from January 5, 2020 to September 5, 2020. The number of new waiting list registrations decreased, with the Northeast seeing over a 50% decrease from the week of 3/8 versus the week of 4/5. The national transplant system saw near cessation of living donor transplantation (-90%) from the week of 3/8 to the week of 4/5. Similarly, deceased donor kidney transplant volume dropped from 367 to 202 (-45%), and other organs saw similar decreases: lung (-70%), heart (-43%), and liver (-37%). Deceased donors recovered dropped from 260 to 163 (-45%) from 3/8 compared to 4/5, including a 67% decrease for lungs recovered. The magnitude of this decrease varied by geographic area, with the largest percent change (-67%) in the Northeast. Despite the pandemic, discard rates across organ has remained stable. Although the COVID-19 pandemic continues to evolve, OPTN data show recent evidence of stabilization, an indication that an early recovery of the number of living and deceased donors and transplants has ensued.

APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO): Design and Rationale.

INTRODUCTION: Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes. METHODS: APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys. RESULTS: The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses. CONCLUSION: This article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation.

Can donor narratives yield insights? A natural language processing proof of concept to facilitate kidney allocation.

Although expedited placement could ameliorate stagnant kidney utilization, precisely identifying difficult-to-place organs is crucial to mitigate potential harms associated with this policy. Existing algorithms have only leveraged structured data from the Organ Procurement and Transplantation Network (OPTN); however, detailed, free text case information about a donor exists. No known research exists about the utility of these data. We developed a model to predict the probability of delay or discard for adult deceased kidney donors between 2010 and 2018, leveraging donor free text data. The resultant model had a c-statistic of 0.75 compared to 0.80 ( Reduced Probability of Delay or Discard [model], r-PODD) and 0.77 ( Kidney Donor Profile Index, KDPI) on the test dataset. Analysis of the top predictive words suggest both known and potentially novel clinical factors (ie, a known factor such as hypertension vs a novel factor such as stents), and nuanced social factors (intravenous drug use) could negatively affect kidney utilization. These findings suggest that donor narratives have utility; the natural language processing (NLP) model is only moderately correlated with existing indices and provides directional evidence about additional cardiovascular risk factors that may affect kidney utilization. More research is needed to understand the potential to enhance existing indices of kidney utilization to better enable and mitigate the effects of policy interventions such as expedited placement.

National landscape of HIV+ to HIV+ kidney and liver transplantation in the United States.

The HIV Organ Policy Equity (HOPE) Act, enacted on November 21, 2013, enables research on the transplantation of organs from donors infected with human immunodeficiency virus (HIV) (HIV+) into HIV+ individuals who, prior to transplantation, are infected with HIV. In 2015, the Organ Procurement and Transplantation Network revised organ allocation policies on November 21, and on November 23, the Secretary of Health and Human Services published research criteria and revised the Final Rule accordingly. The HOPE Act appears to be underutilized to date. As of December 31, 2018, there were 56 donors recovered (50 donors transplanted) resulting in 102 organs transplanted (31 liver, 71 kidney). As of December 31, 2018, 212 registrations were indicated on the waiting list as willing to accept an HIV+ kidney or liver, most of which were waiting in active status. Due to the limited number of transplants performed to date, definitive safety conclusions cannot be reached at this time, though current data suggest that 1-year patient and graft survival does not deviate in a major way from that observed in HIV+ recipients of non-HIV+ organs or non-HIV+ recipients. As safety data are reviewed and disseminated, it is anticipated that HOPE participation will increase should safety signals remain low.

Vascularized composite allotransplantation in the United States: A descriptive analysis of the Organ Procurement and Transplantation Network Data.

On July 3, 2014, the Organ Procurement and Transplantation Network/United Network for Organ Sharing was charged with the oversight of vascularized composite allograft (VCA) procurement and transplantation in the United States. As of December 31, 2017, 61 VCA programs at 27 centers were approved in the United States. Fifty candidates have been added to the waiting list at 15 centers. Twenty-eight VCA transplants have been performed at 14 programs (10 upper limb, 10 uterus, 5 craniofacial, 1 scalp, 1 abdominal wall, and 1 penile). Twenty-two VCAs were procured from 21 deceased donors, resulting in 109 non-VCA organs transplanted (15 hearts, 3 intestine, 40 kidney, 20 livers, 24 lungs, and 7 pancreata). Six uterus transplants were performed from living donors. Fourteen candidates were still waiting at 9 centers on December 31, 2017. Two of the 10 uterus recipients had live births and 3 still had viable grafts. Seventeen of 18 nonuterus recipients had functioning grafts. At present, VCA is an emerging field with a small number of patients transplanted. Data on posttransplant survival and functional outcomes continue to be collected to further the understanding of this complex and evolving field. Further systematic data are important for policy refinement and assurance of patient safety.

VCA Deceased Donors in the United States.

BACKGROUND: Vascularized composite allograft (VCA) transplants include diverse organ types and are made possible primarily by deceased donors. METHODS: We used Organ Procurement and Transplantation Network data to characterize VCA deceased donors (n = 66 of 70) in the United States from 1998 to 2017 and compare their characteristics with those of kidney donors in 2017. RESULTS: Through December 31, 2017, 20 transplant programs performed 72 deceased-donor VCA transplants, with organs donated by 70 donors, including 30 upper limb (17 unilateral and 13 bilateral) and 11 face donors. Other donors donated both upper limbs and face (n = 2), uterus (n = 4), abdominal wall (n = 19), larynx (n = 2), penis (n = 1), and scalp (n = 1). About a third of VCA donors were female, and the majority (86.4%) were white. Almost half (45.5%) were between the ages 18 and 34 years. Smaller proportions were younger than 18 years (19.7%), 35 to 44 years (15.2%), 45 to 54 years (13.6%), and older than 55 years (6.1%). Median body mass index for all VCA donors was 24.9 and varied widely, especially for upper limb and face donors. There was considerable variation in Kidney Donor Profile Index among VCA donors (median, 27.5; interquartile range, 11-59). Donor causes of death included head trauma (39.4%), cerebrovascular/stroke (25.8%), and anoxia (31.8%). VCA donors also donated solid organs that were transplanted, including 87.1% of kidneys, 93.9% of livers, 40.2% of lungs, and 56.1% of hearts. CONCLUSIONS: donors are a demographically and clinically diverse group. Understanding this diversity and future trends in VCA donor characteristics is critical in supporting this life-changing field of transplantation.

OPTN Vascularized Composite Allograft Waiting List: Current Status and Trends in the United States.

BACKGROUND: Vascularized composite allograft (VCA) transplantation is a developing area in the field of transplantation. METHODS: This study used Organ Procurement and Transplantation Network (OPTN) VCA waiting list and transplant data from July 3, 2014 through February 28, 2018, to characterize the OPTN VCA waiting list in terms of composition, removal patterns, waiting time, resulting transplants, and trends over time. RESULTS: Between implementation of the OPTN VCA waiting list on July 3, 2014 and February 28, 2018, 54 candidates-53.7% were male, 79.6% were white, and 70.4% aged 18 to 44 years-were added to the OPTN VCA waiting list. Of these, 22 received deceased donor VCA transplants (6 bilateral upper limb, 4 unilateral upper limb, 5 craniofacial, 1 scalp, 1 abdominal wall, 1 penile, and 4 uterine), and 6 received living donor uterine transplants. Registrations increased in 2016 after uterine and penile transplants were introduced in the United States, resulting in a large shift in the composition of the VCA waiting list. Waiting times for VCA candidates vary greatly, with some VCA candidates receiving deceased donor transplants quickly and others waiting more than 3 years before transplantation. CONCLUSIONS: The field of VCA transplantation and the composition of the OPTN VCA waiting list are evolving rapidly. Additional research is needed to understand these changes and investigate whether differences in need or differences in access have resulted in the variation seen on the VCA waiting list.

Social, economic, and policy implications of organ preservation advances.

PURPOSE OF REVIEW: Despite over 60 years of progress in the field of since the first organ transplant, insufficient organ preservation capabilities still place profound constraints on transplantation. These constraints play multiple and compounding roles in the predominant limitations of the field: the severe shortages of transplant organs, short-term and long-term posttransplant outcomes and complications, the unmet global need for development of transplant infrastructures, and economic burdens that limit patient access to transplantation and contribute to increasing global healthcare costs. This review surveys ways that advancing preservation technologies can play a role in each of these areas, ultimately benefiting thousands if not millions of patients worldwide. RECENT FINDINGS: Preservation advances can create a wide range of benefits across many facets of organ transplantation, as well as related areas of transplant research. As these technologies mature, so will the policies around their use to maximize the benefits offered by organ preservation. SUMMARY: Organ preservation advances stand to increase local and global access to transplantation, improve transplant outcomes, and accelerate progress in related areas such as immune tolerance induction and xenotransplantation. This area holds the potential to save the healthcare system many billions of dollars and reduce costs across many aspects of transplantation. Novel preservation technologies, along with other technologies facilitated by preservation advances, could potentially save millions of lives in the coming years.

Risk of ESRD in prior living kidney donors.

We studied End-Stage Renal Disease (ESRD) in living kidney donors (LKDs) who donated in the United States between 1994 and 2016 (n = 123 526), using Organ Procurement and Transplantation Network and Centers for Medicare and Medicaid Services data. Two hundred eighteen LKDs developed ESRD, with a median of 11.1 years between donation and ESRD. Absolute 20-year risk was low but not uniform, with risk associated with race, age, and sex and increasing exponentially over time. LKDs had increased risk of ESRD if they were male (adjusted hazard ratio [aHR]: 1.75, 95% confidence interval [95%CI]: 1.33-2.31), had higher BMI (aHR: 1.34 per 5 kg/m2 , 95%CI: 1.10-1.64) or lower estimated GFR (aHR: 0.89 per 10 mL/min, 95% CI: 0.80-0.99), were first-degree relatives of the recipient (parent: [aHR: 2.01, 95% CI: 1.26-3.21]; full sibling [aHR: 1.87, 95%CI: 1.23-2.84]; identical twin [aHR: 19.79, 95%CI: 7.65-51.24]), or lived in lower socioeconomic status neighborhoods at donation (aHR: 0.87 per $10k increase; 95%CI: 0.77-0.99). We found a significant interaction between donation age and race, with higher risk at older ages for white LKDs (aHR: 1.26 per decade, 95%CI: 1.04-1.54), but higher risk at younger ages for black LKDs (aHR: 0.75 per decade, 95%CI: 0.57-0.99). These findings further inform risk assessment of potential LKDs.

Early Experience with the New Kidney Allocation System: A Perspective from UNOS.

PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_21_CJASNPodcast_18_1_v.mp3.

Diagnosing the Decades-Long Rise in the Deceased Donor Kidney Discard Rate in the United States.

BACKGROUND: The proportion of deceased donor kidneys recovered for transplant but discarded increased steadily in the United States over 2 decades, from 5.1% in 1988 to 19.2% by 2009. Over 100 000 patients are waiting for a kidney transplant, yet 3159 kidneys were discarded in 2015. METHODS: We evaluated trends in donor characteristics, discard reasons, and Organ Procurement Organization-specific discard rates. Multivariable regression and propensity analysis were used to estimate the proportion of the discard rate rise in the 2000s attributable to changes in donor factors and decisions to biopsy and pump kidneys. RESULTS: This study found that at least 80% of the discard rate rise can be explained by the recovery of kidneys from an expanding donor pool and changes in biopsy and pumping practices. However, a residual discard rate increase could not be explained by changes in these factors. From 1987 to 2009, median donor age rose from 26 to 43 years; median Kidney Donor Risk Index increased from 1.1 in 1994 to 1.3 in 2009. Our findings suggest that the increase from 10% to 30% in the proportion of kidneys pumped during the 2000s served as a buffer, keeping the discard rate from rising even higher than it did. CONCLUSIONS: The majority of the kidney discard rate rise can be explained by the broadening donor pool. However, the presence of an unexplained, residual increase suggests behavioral factors (eg, increased risk aversion) and/or allocation inefficiencies may have played a role. Reducing risk aversion, improving allocation, and more often pumping less-than-ideal, yet potentially transplantable kidneys, may help reverse the trend.

Delays in Prior Living Kidney Donors Receiving Priority on the Transplant Waiting List.

BACKGROUND AND OBJECTIVES: Prior living donors (PLDs) receive very high priority on the Organ Procurement and Transplantation Network (OPTN) kidney waiting list. Program delays in adding PLDs to the waiting list, setting their status to active, and submitting requests for PLD priority can affect timely access to transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used the OPTN and the Centers for Medicare and Medicaid Services data to examine timing of (1) listing relative to start of dialysis, (2) activation on the waiting list, and (3) requests for PLD priority relative to listing date. There were 210 PLDs (221 registrations) added to the OPTN kidney waiting list between January 1, 2010 and July 31, 2015. RESULTS: As of September 4, 2015, 167 of the 210 PLDs received deceased donor transplants, six received living donor transplants, two died, five were too sick to transplant, and 29 were still waiting. Median waiting time to deceased donor transplant for PLDs was 98 days. Only 40.7% of 221 PLD registrations (n=90) were listed before they began dialysis; 68.3% were in inactive status for <90 days, 17.6% were in inactive status for 90-365 days, 8.6% were in inactive status for 1-2 years, and 5.4% were in inactive status for >2 years. Median time of PLDs waiting in active status before receiving PLD priority was 2 days (range =0-1450); 67.4% of PLDs received PLD priority within 7 days after activation, but 15.4% waited 8-30 days, 8.1% waited 1-3 months, 4.1% waited 3-12 months, and 5.0% waited >1 year in active status for PLD priority. After receiving priority, most were transplanted quickly. Median time in active status with PLD priority before deceased donor transplant was 23 days. CONCLUSIONS: Fewer than one half of listed PLDs were listed before starting dialysis. Most listed PLDs are immediately set to active status and receive PLD priority quickly, but a substantial number spends time in active status without PLD priority or a large amount of time in inactive status, which affects access to timely transplants.

Safety of belatacept bridging immunosuppression in hepatitis C-positive liver transplant recipients with renal dysfunction.

BACKGROUND: Perioperative renal dysfunction in liver transplant recipients complicates maintenance immunosuppressive therapy, particularly in patients with hepatitis C. Calcineurin inhibitors exacerbate renal dysfunction and mammalian target-of-rapamycin inhibitors are generally avoided because of perceived perioperative risks. The authors' experience with seven liver transplant patients who received belatacept and mycophenolic acid maintenance immunosuppression is reported. METHODS: A retrospective review of adult liver transplant recipients with hepatitis C receiving belatacept was conducted under Institutional Review Board approval. All patients were Epstein-Barr virus IgG seropositive. The primary endpoint was patient and graft survival, with secondary endpoints including the incidence of acute rejection, degree of renal function recovery, and occurrence of major side effects. RESULTS: Between December 19, 2011 and January 25, 2013, seven liver transplant recipients with hepatitis C received belatacept immunosuppression in the perioperative period. The primary indication for belatacept was perioperative renal dysfunction. Belatacept was initiated between 2 and 90 days posttransplant and the duration of belatacept therapy ranged from 19 to 89 days. Patients were transitioned onto calcineurin inhibitor therapy when they reached chronic kidney disease stage 2 or better. Six-month patient and graft survival was 86%. There was one episode of graft rejection on belatacept therapy in a patient who had also had early rejection before initiation of belatacept. CONCLUSIONS: The results in this initial group of patients suggest that belatacept with mycophenolic acid may be a safe maintenance immunosuppression regimen in hepatitis C-positive liver transplant recipients with renal dysfunction, and that this regimen can serve as an effective bridge to calcineurin inhibitor therapy.