The Evolution and Direction of OPTN Oversight of Live Organ Donation and Transplantation in the United States

For more than 20 years, the Organ Procurement and Transplantation Network (OPTN) has developed policies and bylaws relating to equitable allocation of deceased donor organs for transplantation. United Network for Organ Sharing (UNOS) operates the OPTN under contract with the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS). Until recent years, the OPTN had little defined authority regarding living donor organ for transplantation except for the collection of data relating to living donor transplants.
Beginning with the implementation of the OPTN Final Rule in 2000, and continuing with more recent announcements, the OPTN's role in living donation has grown. Its responsibilities now include monitoring of living donor outcomes, promoting equity in nondirected living donor transplantation and ensuring that transplant programs have expertise and established protocols to promote the safety of living donors and recipients. The purpose of this article is to describe the evolving mandates for the OPTN in living donation, as well as the network's recent activities and ongoing efforts.     

The benefit to waitlist patients in a national paired kidney exchange program: Exploring characteristics of chain end living donor transplants

Nondirected kidney donors can initiate living donor chains that end to patients on the waitlist. We compared 749 National Kidney Registry (NKR) waitlist chain end transplants to other transplants from the NKR and the Scientific Registry of Transplant Recipients between February 2008 and September 2020. Compared to other NKR recipients, chain end recipients were more often older (53 vs. 52 years), black (32% vs. 15%), publicly insured (71% vs. 46%), and spent longer on dialysis (3.0 vs. 1.0 years). Similar differences were noted between chain end recipients and non-NKR living donor recipients. Black patients received chain end kidneys at a rate approaching that of deceased donor kidneys (32% vs. 34%). Chain end donors were older (52 vs. 44 years) with slightly lower glomerular filtration rates (93 vs. 98 ml/min/1.73 m²) than other NKR donors. Chain end recipients had elevated risk of graft failure and mortality compared to control living donor recipients (both p < .01) but lower graft failure (p = .03) and mortality (p < .001) compared to deceased donor recipients. Sharing nondirected donors among a multicenter network may improve the diversity of waitlist patients who benefit from living donation.     

Revaluation and lessons learned from the first 9 cases of a Czech uterus transplantation trial: Four deceased donor and 5 living donor uterus transplantations

Although uterus transplantation is still in the experimental stage, it has promising potential as a treatment for women with absolute uterine factor infertility based on the childbirths from living donor trials conducted in Sweden and the United States. We report the main characteristics and perioperative and postoperative courses of both recipients and donors following 4 deceased donor and 5 living donor uterus transplantations. Three main priorities differentiate this study from the previously reported uterus transplantations. First, clinical experience with the largest worldwide group of deceased donor uterine transplants is described. Second, in the majority of living donor uterine recipients, only 2 ovarian veins were used for venous blood outflow. All of these recipient procedures were surgically successful, and follow‐up posttransplant ultrasound examinations revealed normal uterine blood supply and outflow. Third, in only one living and one deceased donor recipient, the transplanted uterus relied on only 2 uterine veins for venous outflow with a 50% surgical success rate. In all other recipients, 2 uterine and 2 ovarian veins were utilized. Although a successful pregnancy has not yet been achieved, the presented surgical and functional results of our trial are promising.     

Improving Organ Utilization to Help Overcome the Tragedies of the Opioid Epidemic

Death rates from drug overdoses have nearly doubled since 2003, with over 47 000 deaths in 2014. This is largely attributable to the opioid epidemic. If the unfortunate deaths of otherwise healthy people have yielded an increase in organ donors, then this might serve as perhaps the only comforting factor among this tragic and unnecessary loss of life. In this viewpoint, we present data from the Organ Procurement and Transplantation Network (OPTN) that show how the greatest relative increases in the mechanism of death among deceased donors from 2003 to 2014 were drug overdoses. Unfortunately, despite the absolute increase in the number of donors who died from a drug overdose, the mean organ yield was significantly lower than in other categories, in part due to concerns about disease transmission. In this paper, we present data on the changes in donation from donors with a drug overdose as a result of the opioid epidemic and discuss the need to educate transplant candidates and their physicians about the low risk of disease transmission compared to the greater risk of dying on a transplant waitlist.     

Optimizing Outcomes in Pediatric Renal Transplantation Through the Australian Paired Kidney Exchange Program

Kidney paired donation (KPD) programs offer the opportunity to enable living kidney donation when immunological and other barriers prevent safe directed donation. Children are likely to require multiple transplants during their lifetime; therefore, high‐level histocompatibility and organ quality matching are key priorities. Details are given for a cohort of seven pediatric renal transplantations performed through the Australian Kidney Exchange (AKX), including barriers to alternative transplantation and outcomes after KPD. Reasons for entering the KPD program were preformed donor‐specific antibodies to their registered donor in five cases, ABO mismatch, and avoidance of the risk of exposure to hepatitis B virus. Four recipients were highly sensitized. All patients received transplants with organs of lower immunological risk compared with their registered donors. HLA eplet mismatch scores were calculated for donor–recipient pairs; three patients had improved eplet mismatch load with AKX donor compared with their registered donor. All grafts are functioning, with a mean estimated glomerular filtration rate of 77 mL/min/1.73 m² (range 46–94 mL) and a follow‐up range of 8–54 months, and no patient experienced clinical or histological rejection. KPD is a viable strategy to overcome many barriers to living donation for pediatric patients who have an otherwise suitable donor and provides an opportunity to minimize immunological risks.     

Successful living donor intestinal transplantation in crossmatch positive recipients: Initial experience

Sensitized patients tend to have longer waiting times on the deceased donor list and are at increased risk of graft loss from acute or chronic rejection compared to non-sensitized candidates. Desensitization protocols are utilized to decrease the levels of alloantibodies and to convert an initial positive cross-match to prospective donors into a negative crossmatch. These procedures are mostly available in the setting of living donation. Due to the elective nature of the procedure, desensitization protocols can be extended until the desire result is obtained prior to transplantation. We present two cases of successful desensitization protocol applied to living donor intestinal transplant candidates that converted to negative cross-match to their donors. We present two cases of intestinal transplant candidates with a potential living donor to whom they are sensitized. Both cases underwent successful transplantation after desensitization protocol. No evidence of humoral rejection has occurred in either recipient. Living donor intestinal transplantation in sensitized recipients against the prospective donors provides the ability to implement a desensitization protocol to convert to negative crossmatch.     

Organ donation and utilization in the USA

The processes leading to donor identification, consent, organ procurement, and allocation continue to dominate debates and efforts in the field of transplantation. A considerable shortage of donors remains while the number of patients needing organ transplantation increases.
This article reviews the main trends in organ donation practices and procurement patterns from both deceased and living sources in the USA. Although there have been increases in living donation in recent years, 2002 witnessed a much more modest growth of 1%. Absolute declines in living liver and lung donation were also noted in 2002.
In 2002, the number of deceased donors increased by only 1.6% (101 donors). Increased donation from deceased donors provides more organs for transplantation than a comparable increase in living donation, because on average 3.6 organs are recovered from each deceased donor. The total number of organs recovered from deceased donors increased by 2.1% (462 organs). Poor organ quality continued to be the major reason given for nonrecovery of consented organs from deceased donors.
The kidney is the organ most likely to be discarded after recovery. Over the past decade the discard rate of recovered kidneys has increased from 6% to 11%. Many of these are expanded criteria donor kidneys.     

Direction of the Organ Procurement and Transplantation Network and United Network for Organ Sharing Regarding the Oversight of Live Donor Transplantation and Solicitation for Organs

The Organ Procurement and Transplantation Network (OPTN) operated by United Network for Organ Sharing (UNOS) has taken recent steps to address public solicitation for organ donors and its oversight of live donor transplantation. This report provides the direction of the OPTN regarding deceased donor solicitation. The OPTN has authority under federal law to equitably allocate deceased donor organs within a single national network based upon medical criteria, not upon one's social or economic ability to utilize resources not available to all on the waiting list. The OPTN makes a distinction between solicitations for a live donor organ versus solicitations for directed donation of deceased organs. As to live donor solicitation, the OPTN cannot regulate or restrict ways relationships are developed in our society, nor does it seek to do so. OPTN members have a responsibility of helping protect potential recipients from hazards that can arise from public appeals for live donor organs. Oversight and support of the OPTN for live donor transplantation is now detailed by improving the reporting of live donor follow-up, by providing a mechanism for facilitating anonymous live kidney donation, and by providing information for potential live kidney donors via the UNOS Transplant Living website.     

Recipient Outcomes Following Transplantation of Allografts From Live Kidney Donors Who Subsequently Developed End‐Stage Renal Disease

Live kidney donors have an increased risk of end‐stage renal disease (ESRD) compared with nondonors; however, it is unknown whether undetected, subclinical kidney disease exists at donation that subsequently contributes to this risk. To indirectly test this hypothesis, the authors followed the donated kidneys, by comparing the outcomes of 257 recipients whose donors subsequently developed ESRD with a matched cohort whose donors remained ESRD free. The compared recipients were matched on donor (age, sex, race/ethnicity, donor–recipient relationship), transplant (HLA mismatch, peak panel‐reactive antibody, previous transplantation, year of transplantation), and recipient (age, sex, race/ethnicity, body mass index, cause of ESRD, and time on dialysis) risk factors. Median recipient follow‐up was 12.5 years (interquartile range 7.4–17.9, maximum 20 years). Recipients of allografts from donors who developed ESRD had increased death‐censored graft loss (74% versus 56% at 20 years; adjusted hazard ratio [aHR] 1.7; 95% confidence interval [CI] 1.5–2.0; p < 0.001) and mortality (61% versus 46% at 20 years; aHR 1.5; 95% CI 1.2–1.8; p < 0.001) compared with matched recipients of allografts from donors who did not develop ESRD. This association was similar among related, spousal, and unrelated nonspousal donors. These findings support a novel view of the mechanisms underlying donor ESRD: that of pre‐donation kidney disease. However, biopsy data may be required to confirm this hypothesis.     

Kidney Transplantation From a Donor With Sickle Cell Disease

In the United States, >100 000 patients are waiting for a kidney transplant. Given the paucity of organs available for transplant, expansion of eligibility criteria for deceased donation is of substantial interest. Sickle cell disease (SCD) is viewed as a contraindication to kidney donation, perhaps because SCD substantially alters renal structure and function and thus has the potential to adversely affect multiple physiological processes of the kidney. To our knowledge, transplantation from a donor with SCD has never been described in the literature. In this paper, we report the successful transplantation of two kidneys from a 37‐year‐old woman with SCD who died from an intracranial hemorrhage. Nearly 4 mo after transplant, both recipients are doing well and are off dialysis. The extent to which kidneys from donors with SCD can be safely transplanted with acceptable outcomes is unknown; however, this report should provide support for the careful expansion of kidneys from donors with SCD without evidence of renal dysfunction and with normal tissue architecture on preimplantation biopsies.     

Long‐term impact and clinical significance of living donor liver transplantation with respect to donor liver restoration and spleen size: A prospective study

This study aimed to evaluate postoperative long‐term liver restoration and splenic enlargement and their clinical significance in living donor liver transplantation. One hundred and sixteen donors who had donated livers more than 5 years previously accepted the invitation to participate in this study. The liver restoration rate and the splenic enlargement rate were calculated as the rate with respect to the original volume. The mean liver restoration rate was 0.99 ± 0.12 and older age was associated with a higher incidence for liver restoration rate <0.95 (P = .005), whereas type of donor operation was not. The donors with liver restoration rate <0.95 showed lower serum albumin levels than those with liver restoration rate ≥0.95. The mean splenic enlargement rate was 1.10 ± 0.16. Right lobe donors demonstrated higher splenic enlargement rate (1.14 ± 0.18) than left lobe/lateral segment donors (1.06 ± 0.13). In the donors with splenic enlargement rate ≥1.10, platelet count was not fully restored to the preoperative level. In conclusion, older age increases the risk for incomplete postoperative liver restoration, which may be associated with a decrease in albumin more than 5 years after donation. Right lobe donation poses a risk of splenic enlargement, which is associated with incomplete restoration of platelet count.     

Considering Tangible Benefit for Interdependent Donors: Extending a Risk–Benefit Framework in Donor Selection

From its infancy, live donor transplantation has operated within a framework of acceptable risk to donors. Such a framework presumes that risks of living donation are experienced by the donor while all benefits are realized by the recipient, creating an inequitable distribution that demands minimization of donor risk. We suggest that this risk‐tolerance framework ignores tangible benefits to the donor. A previously proposed framework more fully considers potential benefits to the donor and argues that risks and benefits must be balanced. We expand on this approach, and posit that donors sharing a household with and/or caring for a potential transplant patient may realize tangible benefits that are absent in a more distantly related donation (e.g. cousin, nondirected). We term these donors, whose well‐being is closely tied to their recipient, “interdependent donors.” A flexible risk–benefit model that combines risk assessment with benefits to interdependent donors will contribute to donor evaluation and selection that more accurately reflects what is at stake for donors. In so doing, a risk–benefit framework may allow some donors to accept greater risk in donation decisions.     

Histopathologic evaluation of living kidney donor candidates by pre-operative kidney biopsy

Abstract:  A lack of deceased kidney donors in Japan has led to dependence on living donors in as many as 80% of cases. At the same time, indications for living-donor kidney donation have been expanding in terms of donor medical status as well as HLA matching and ABO compatibility, thus emphasizing the donor shortage. To facilitate final medical decision-making for living kidney donation, we attempted kidney biopsy in six donor candidates who had problems such as mild diabetes and slight proteinuria. The biopsy specimens showed various degrees of tissue injury ranging from partial glomerular sclerosis to arteriole hyalinization. On the basis of the biopsy findings, kidney donation was subsequently performed in three of the six cases with full informed consent, and not done in the remaining three cases. Longer-term studies will be needed to clarify the outcome in both the donors and recipients in these cases.     

Kidney exchange match rates in a large multicenter clearinghouse

Kidney paired donation (KPD) can facilitate living donor transplantation for candidates with an incompatible donor, but requires waiting for a match while experiencing the morbidity of dialysis. The balance between waiting for KPD vs desensitization or deceased donor transplantation relies on the ability to estimate KPD wait times. We studied donor/candidate pairs in the National Kidney Registry (NKR), a large multicenter KPD clearinghouse, between October 2011 and September 2015 using a competing‐risk framework. Among 1894 candidates, 52% were male, median age was 50 years, 66% were white, 59% had blood type O, 42% had panel reactive antibody (PRA)>80, and 50% obtained KPD through NKR. Median times to KPD ranged from 2 months for candidates with ABO‐A and PRA 0, to over a year for candidates with ABO‐O or PRA 98+. Candidates with PRA 80‐97 and 98+ were 23% (95% confidence interval , 6%‐37%) and 83% (78%‐87%) less likely to be matched than PRA 0 candidates. ABO‐O candidates were 67% (61%‐73%) less likely to be matched than ABO‐A candidates. Candidates with ABO‐B or ABO‐O donors were 31% (10%‐56%) and 118% (82%‐162%) more likely to match than those with ABO‐A donors. Providers should counsel candidates about realistic, individualized expectations for KPD, especially in the context of their alternative treatment options.     

ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies: a propensity-matched analysis

Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO-incompatible (ABOi) kidney transplantation with matched ABO-compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. We performed a retrospective study with propensity matching and compared patient and death-censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. 296 ABOi were compared with 1184 center and propensity-matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group, and PRA). Patient survival was better compared with deceased donor [hazard ratio (HR) for death of HR 0.69 (0.49–0.96)] and non-significantly different from ABOc living donor recipients [HR 1.28 (0.90–1.81)]. Rate of graft failure was higher compared with ABOc living donor transplantation [HR 2.63 (1.72–4.01)]. Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab-treated recipients (P < 0.001). ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared with matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy [NTR7587, www.trialregister.nl ].     

Psychological Outcomes of Living Liver Donors From a Multicenter Prospective Study: Results From the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL‐2)

Although single‐center and cross‐sectional studies have suggested a modest impact of liver donation on donor psychological well‐being, few studies have assessed these outcomes prospectively among a large cohort. We conducted one of the largest, prospective, multicenter studies of psychological outcomes in living liver donors within the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL‐2) consortium. In total, 271 (91%) of 297 eligible donors were interviewed at least once before donation and at 3, 6, 12, and 24 mo after donation using validated measures. We found that living liver donors reported low rates of major depressive (0–3%), alcohol abuse (2–5%), and anxiety syndromes (2–3%) at any given assessment in their first 2 years after donation. Between 4.7% and 9.6% of donors reported impaired mental well‐being at various time points. We identified significant predictors for donors’ perceptions of being better people and experiencing psychological growth following donation, including age, sex, relationship to recipient, ambivalence and motivation regarding donation, and feeling that donation would make life more worthwhile. Our results highlight the need for close psychosocial monitoring for those donors whose recipients died (n=27); some of those donors experienced guilt and concerns about responsibility. Careful screening and targeted, data‐driven follow‐up hold promise for optimizing psychological outcomes following this procedure for potentially vulnerable donors.     

Solid organ donation after death in the United States: Data‐driven messaging to encourage potential donors

US deceased donor solid organ transplantation (dd‐SOT) depends upon an individual's/family's altruistic willingness to donate organs after death; however, there is a shortage of deceased organ donors in the United States. Informing individuals of their own lifetime risk of needing dd‐SOT could reframe the decision‐making around organ donation after death. Using United Network for Organ Sharing (UNOS) data (2007‐2016), this cross‐sectional study identified (1) deceased organ donors, (2) individuals waitlisted for dd‐SOT (liver, kidney, pancreas, heart, lung, intestine), and (3) dd‐SOT recipients. Using US population projections, life tables, and mortality estimates, we quantified probabilities (Pr) of (1) becoming deceased organ donors, (2) needing dd‐SOT, and (3) receiving dd‐SOT. Lifetime Pr (per 100 000 US population) for males and females of becoming deceased organ donors were 212 and 146, respectively, and of needing dd‐SOT were 1323 and 803, respectively. Lifetime Pr of receiving dd‐SOT was 50% for males, 48% for females. Over a lifetime, males were 6.2 and females 5.5 times more likely to need dd‐SOT than to become deceased organ donors. Organ donation is traditionally contextualized in terms of charity toward others. Our analyses yield a new tool, in the form of quantifying an individual's own likelihood of needing dd‐SOT, which may assist with reframing motivations toward deceased donor organ donation.     

Dengue virus transmission from live donor liver graft

Arboviral transmission through transplanted organs is rare. We report a highly probable case of dengue viral transmission during live donor liver transplantation. Fever with severe thrombocytopenia was observed in the donor and recipient within 6 and 9 days after transplantation, respectively. Dengue diagnosis was confirmed by testing blood and explant tissue from the donor and recipient using dengue‐specific NAT (nucleic acid testing) and serology. Serology indicated the donor had secondary dengue infection that ran a mild course. However, the dengue illness in the recipient was severe and deteriorated rapidly, eventually proving fatal. The recipient's explant liver tissue tested negative for viral RNA indicative of a pretransplant naïve status. The prM–Envelope gene sequence analysis of the donor and recipient viral RNA identified a similar serotype (DENV1) with almost 100% sequence identity in the envelope region. Molecular phylogenetic analysis of donor and recipient viral envelope sequences with regional and local dengue strains further confirmed their molecular similarity, suggesting a probable donor‐to‐recipient transmission via organ transplantation. Screening of living donors for dengue virus may be considered in endemic regions.     

Kidney and Pancreas Transplantation in the United States, 1995–2004

This article examines OPTN/SRTR data on kidney and pancreas transplantation for 2004 and the previous decade, and discusses recent changes in kidney-pancreas (KP) allocation policy and emerging issues in kidney donation after cardiac death (DCD). Although the number of kidney donors continues to increase, new waiting list registrations again outpaced the number of kidney transplants performed, rising by 11% between 2003 and 2004 and contributing to a 1-year increase of 8% in the number of patients active on the waiting list. DCD has increased steadily since 2000; 39% more DCD transplants were performed in 2004 than 2003. Both deceased donor and living donor kidney graft survival rates remain excellent and are improving. The number of people living with a functioning kidney transplant doubled between 1995 and 2004, to 101 440 with a functioning kidney-alone and 7213 with a functioning KP. Health care providers in all settings are more likely to be exposed to these transplant recipients. Patient survival following simultaneous pancreas-kidney (SPK) transplantation is excellent and has improved incrementally since 1995; death rates in the first year fell from 60 per 1000 patient-years at risk in 2001 to 45 in 2003. The number of solitary pancreas transplants increased dramatically in 2004.