Information design to support growth, quality, and equity of the US transplant system.

The Organ Procurement and Transplantation Network, an arm of the Health Resources and Services Administration, has a contract with the United Network for Organ Sharing since 1986 to provide central oversight of organ donation and transplants in the United States. The United Network for Organ Sharing has recently come under scrutiny, prompting a review by the National Academies of Sciences, Engineering, and Medicine as summarized in its recent report and also by the US Senate Finance Committee. The national news services have opined about organ donation ethics, access to transplantation particularly for medically underserved populations, and management of organ transplantation data. These critiques raise important concerns that deserve our best response as a transplant community. Broadly, we suggest that the data management approach of the Organ Procurement and Transplantation Network be replaced with a patient-centric omnichannel network in which all donor and recipient data exist in a single longitudinal record that can be used by all applications. A more comprehensive and standardized approach to donor data collection would drive quality improvement across organ procurement organizations and help address inequities in transplantation. Finally, a substantial increase in organ donation would be prompted by considering organ donors as a public health resource, meriting transparent publicly available data collection with respect to organ donor referral, screening, and management.

Honoring the gift: The transformative potential of transplant-declined human organs.

For decades, transplantation has been a life-saving treatment for those fortunate enough to gain access. Nevertheless, many patients die waiting for an organ and countless more never make it onto the waitlist because of a shortage of donor organs. Concurrently, thousands of donated organs are declined for transplant each year because of concerns about poor outcomes post-transplant. The decline of any donated organ-even if medically justified-is tragic for both the donor family and potential recipients. In this Personal Viewpoint, we discuss the need for a new mindset in how we honor the gift of organ donation. We believe that the use of transplant-declined human organs in translational research has the potential to hasten breakthrough discoveries in a multitude of scientific and medical areas. More importantly, such breakthroughs will allow us to properly value every donated organ. We further discuss the many practical challenges that such research presents and offer some possible solutions based on experiences in our own research laboratories. Finally, we share our perspective on what we believe are the necessary next steps to ensure a future where every donated organ realizes its full potential to impact the lives of current and future patients.

A regulated system of incentives for living kidney donation: Clearing the way for an informed assessment.

The kidney shortage continues to be a crisis for our patients. Despite numerous attempts to increase living and deceased donation, annually in the United States, thousands of candidates are removed from the kidney transplant waiting list because of either death or becoming too sick to transplant. To increase living donation, trials of a regulated system of incentives for living donation have been proposed. Such trials may show: (1) a significant increase in donation, and (2) that informed, incentivized donors, making an autonomous decision to donate, have the same medical and psychosocial outcomes as our conventional donors. Given the stakes, the proposal warrants careful consideration. However, to date, much discussion of the proposal has been unproductive. Objections commonly leveled against it: fail to engage with it; conflate it with underground, unregulated markets; speculate without evidence; and reason fallaciously, favoring rhetorical impact over logic. The present paper is a corrective. It identifies these common errors so they are not repeated, thus allowing space for an assessment of the proposal on its merits.

COVID-19 and transplantation-Data censoring.

During the early wave of the COVID-19 pandemic, the Scientific Registry of Transplant Recipients (SRTR) designated a "black out" period between March 12, 2020, and June 12, 2020, for transplant outcomes reporting. We discuss the implications and potential bias it has introduced as it may selectively favor the outcomes for certain regions and harm other regions due to varied effects of different waves of COVID-19 infections across the United States.

Wanted: An endothelial cell targeting atlas for nanotherapeutic delivery in allograft organs.

Despite the profound shortage of organs available for transplant in the U.S., over 5,000 donated organs were declined for use in 2020. Many of these organs were declined due to donor comorbidities or preservation injuries that predispose grafts to rejection and loss. The risks of these poor outcomes can potentially be reduced by pre-transplant application of normothermic machine perfusion (NMP). To date, the clinical use of NMP has focused on extending preservation and improving organ assessment, but the opportunity for ex situ therapeutic delivery may be the most transformative aspect of this technology. In this Personal Viewpoint, we argue that the endothelial cells (ECs) that line the graft vasculature are an accessible, under-exploited, and attractive target for transplant therapeutics delivered during NMP. We further contend that molecularly targeted nanoparticles (NPs) represent a promising therapeutic vehicle particularly well-suited to NMP. However, to achieve this potential, we need to answer the following three key questions: (1) What EC sub-populations exist within an organ? (2) How can these cells be accessed? (3) And most important, how can preferential retention of NPs by the cells of interest be maximized? Here we argue for creating an EC-targeting atlas as a body of knowledge that answers these questions.

Challenges encountered in conducting donor-based research: Lessons learned from the Donor Heart Study.

Solid organ transplantation continues to be constrained by a lack of suitable donor organs. Advances in donor management and evaluation are needed to address this shortage, but the performance of research studies in deceased donors is fraught with challenges. Here we discuss several of the major obstacles we faced in the conduct of the Donor Heart Study-a prospective, multi-site, observational study of donor management, evaluation, and acceptance for heart transplantation. These included recruitment and engagement of participating organ procurement organizations, ambiguities related to study oversight, obtaining authorization for donor research, logistical challenges encountered during donor management, sustaining study momentum, and challenges related to study data management. By highlighting these obstacles encountered, as well as the solutions implemented, we hope to stimulate further discussion and actions that will facilitate the design and execution of future donor research studies.

Inflammation in the early phase after kidney transplantation is associated with increased long-term all-cause mortality.

In the general population, low-grade inflammation has been established as a risk factor for all-cause mortality. We hypothesized that an inflammatory milieu beyond the time of recovery from the surgical trauma could be associated with increased long-term mortality in kidney transplant recipients (KTRs). This cohort study included 1044 KTRs. Median follow-up time post-engraftment was 10.3 years. Inflammation was assessed 10 weeks after transplantation by different composite inflammation scores based on 21 biomarkers. We constructed an overall inflammation score and five pathway-specific inflammation scores (fibrogenesis, vascular inflammation, metabolic inflammation, growth/angiogenesis, leukocyte activation). Mortality was assessed with Cox regression models adjusted for traditional risk factors. A total of 312 (29.9%) patients died during the follow-up period. The hazard ratio (HR) for death was 4.71 (95% CI: 2.85-7.81, p < .001) for patients in the highest quartile of the overall inflammation score and HRs 2.35-2.54 (95% CI: 1.40-3.96, 1.52-4.22, p = .001) for patients in the intermediate groups. The results were persistent when the score was analyzed as a continuous variable (HR 1.046, 95% CI: 1.033-1.056, p < .001). All pathway-specific analyses showed the same pattern with HRs ranging from 1.19 to 2.70. In conclusion, we found a strong and consistent association between low-grade systemic inflammation 10 weeks after kidney transplantation and long-term mortality.

Response to American College of Physician's statement on the ethics of transplant after normothermic regional perfusion.

This paper responds to the position statement released by the American College of Physicians (ACP) entitled "Ethics, Determination of Death, and Organ Transplantation in Normothermic Regional Perfusion (NRP) with Controlled Donation after Circulatory Determination of Death (cDCD): American College of Physicians Statement of Concern." The ACP's statement engages with critical ethical issues surrounding cDCD NRP, but several of their conclusions are flawed. Contrary to the statement, the practice respects the dead donor rule and the legal definition of death while honoring the wishes of the deceased and their loved ones to help save the lives of those in need of organ transplants. cDCD NRP is well established in many countries, it can enhance trust in medical practice and organ donation, and will increase the availability of optimal organs for life-saving transplants.