Maximizing donors' gifts: A comparison of actual and expected solid organ yield among VCA donors.

Vascularized Composite Allograft (VCA) transplantation provides life-changing transplants, but VCA adds complexity to the donation process and timing, possibly impeding solid organ donation. Expanding upon descriptive analyses, this study examines risk-adjusted predictions versus the observed number of organs donated by VCA donors. Our cohort included VCA donors in the United States during January 1, 2008-December 31, 2017 (n = 51), using OPTN Deceased Donor Registration Form data and the Scientific Registry of Transplant Recipients (SRTR) donor yield models to calculate observed-to-expected (O:E) yield ratios. Almost all VCA donors' livers (48/51; 94.1%) and kidneys (92/102; 90.2%) were transplanted, with fewer hearts (28/51; 54.9%), lungs (46/102; 45.1%), pancreata (15/51; 29.4%), and intestines (3/51; 5.9%) transplanted. O:E ratios for overall organ yield were slightly greater than expected for VCA donors (1.10; 95% CI: 1.02-1.17). Liver (1.17: 1.08-1.27) and lung yields (1.38: 1.07-1.68) were both greater than expected, while kidney, heart, and pancreas yields were similar to expected. Across VCA types, bilateral upper limb and abdominal wall donors had better-than-expected yields while uterus, face, and unilateral upper limb donors all had similar-to-expected yields. Solid organ yield among VCA donors was as good or better than predicted, suggesting that VCA donation does not compromise recovery and transplantation of lifesaving organs.

The Centers for Medicare and Medicaid Services' proposed metrics for recertification of organ procurement organizations: Evaluation by the Scientific Registry of Transplant Recipients.

On December 23, 2019, the US Centers for Medicare and Medicaid Services proposed 2 new standards that organ procurement organizations (OPOs) must meet for recertification. An OPO's organ donation rate (deceased donors/potential donors) and organ transplant rate (organs transplanted/potential donors) must not fall significantly below the 75th percentile for rates among all OPOs. We examined how OPOs would have fared under the proposed performance standards in 2016-2017. Data on donors and transplants were from the Organ Procurement and Transplantation Network; donor potential was estimated from Detailed Multiple Cause of Death data collected by the Centers for Disease Control and Prevention. In 2017, 31 (53%) OPOs failed to meet the proposed donation rate standard, 36 (62%) failed to meet the proposed organ transplant rate standard, and 37 (64%) failed at least 1 standard. We found that adjusting for age, race, and Hispanic ethnicity altered the evaluation: 8 OPOs changed their pass/fail status for the donation rate and 5 for the proposed organ transplant rate standard. We conclude that the proposed new standards may result in over half of OPOs facing decertification, and risk adjustment suggests that underlying characteristics of deaths vary regionally such that decertification decisions may be affected.

The critical pathway for deceased donation: reportable uniformity in the approach to deceased donation.

The critical pathway of deceased donation provides a systematic approach to the organ donation process, considering both donation after cardiac death than donation after brain death. The pathway provides a tool for assessing the potential of deceased donation and for the prospective identification and referral of possible deceased donors.

Informed Clustering of Donation Service Areas for Improved Benchmarking.

The donation community continuously strives to collaborate and share effective practices to further the mission of saving and healing lives. Donation service areas in which the Organ Procurement Organizations (OPOs) work are multifaceted in their demographics, inciting the Organ Procurement and Transplantation Network to consider a more holistic and objective measure of similarity rather than the size of population alone or locational proximity alone. This would allow OPOs, as a part of their quality improvement efforts, to learn from and mentor other organizations that are dealing with similar challenges. By incorporating multiple informative characteristics together, we can distinguish those likenesses only revealed by taking into account multiple factors simultaneously. We used statistical approaches that take many characteristics of interest describing a donation service area and purposely excluded performance measures that an OPO may be able to influence by their own practices. Unsupervised learning methods combined the original characteristics into a smaller number of new variables, eliminating correlation and overlap in information from the original characteristics, and clustered donation service areas based on the general characteristics and population of the area. This analysis is a first step in providing a different perspective for OPOs to learn from other organizations that may face similar challenges, as well as to share best practices and open new lines of communication.

Correction: The effect of ocean warming on black sea bass (Centropristis striata) aerobic scope and hypoxia tolerance.

[This corrects the article DOI: 10.1371/journal.pone.0218390.].

Can Behavioral Research Improve Transplant Decision-Making? A Mock Offer Study on the Role of Kidney Procurement Biopsies.

Background: The use of procurement biopsies for assessing kidney quality has been implicated as a driver of the nearly 20% kidney discard rate in the United States. Yet in some contexts, biopsies may boost clinical confidence, enabling acceptance of kidneys that would otherwise be discarded. We leveraged a novel organ offer simulation platform to conduct a controlled experiment isolating biopsy effects on offer acceptance decisions. Methods: Between November 26 and December 14, 2018, 41 kidney transplant surgeons and 27 transplant nephrologists each received the same 20 hypothetical kidney offers using a crossover design with weekend "washout" periods. Mini-study 1 included four, low serum creatinine (<1.5 mg/dl) donor offers with arguably "poor" biopsy findings that were based on real offers that were accepted with successful 3-year recipient outcome. For each of the four offers, two experimental variants-no biopsy and "good" biopsy-were also sent. Mini-study 2 included four AKI offers with no biopsy, each having an offer variant with "good" biopsy findings. Results: Among low serum creatinine donor offers, we found approximately threefold higher odds of acceptance when arguably poor biopsy findings were hidden or replaced with good biopsy findings. Among AKI donor offers, we found nearly fourfold higher odds of acceptance with good biopsy findings compared with no biopsy. Biopsy information had profound but variable effects on decision making: more participants appeared to have been influenced by biopsies to rule out, versus rule in, transplantable kidneys. Conclusions: The current use of biopsies in the United States appears skewed toward inducing kidney discard. Several areas for improvement, including reducing variation in offer acceptance decisions and more accurate interpretation of findings, have the potential to make better use of scarce, donated organs. Offer simulation studies are a viable research tool for understanding decision making and identifying ways to improve the transplant system.

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.

The effect of ocean warming on black sea bass (Centropristis striata) aerobic scope and hypoxia tolerance.

Over the last decade, ocean temperature on the U.S. Northeast Continental Shelf (U.S. NES) has warmed faster than the global average and is associated with observed distribution changes of the northern stock of black sea bass (Centropristis striata). Mechanistic models based on physiological responses to environmental conditions can improve future habitat suitability projections. We measured maximum, standard metabolic rate, and hypoxia tolerance (Scrit) of the northern adult black sea bass stock to assess performance across the known temperature range of the species. Two methods, chase and swim-flume, were employed to obtain maximum metabolic rate to examine whether the methods varied, and if so, the impact on absolute aerobic scope. A subset of individuals was held at 30°C for one month (30chronic°C) prior to experiments to test acclimation potential. Absolute aerobic scope (maximum-standard metabolic rate) reached a maximum of 367.21 mgO2 kg-1 hr-1 at 24.4°C while Scrit continued to increase in proportion to standard metabolic rate up to 30°C. The 30chronic°C group exhibited a significantly lower maximum metabolic rate and absolute aerobic scope in relation to the short-term acclimated group, but standard metabolic rate or Scrit were not affected. This suggests a decline in performance of oxygen demand processes (e.g. muscle contraction) beyond 24°C despite maintenance of oxygen supply. The Metabolic Index, calculated from Scrit as an estimate of potential aerobic scope, closely matched the measured factorial aerobic scope (maximum / standard metabolic rate) and declined with increasing temperature to a minimum below 3. This may represent a critical threshold value for the species. With temperatures on the U.S. NES projected to increase above 24°C in the next 80-years in the southern portion of the northern stock's range, it is likely black sea bass range will continue to shift poleward as the ocean continues to warm.

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.

Could more effective use of kidneys recovered from older deceased donors result in more kidney transplants for older patients?

In the face of a severe shortage of kidneys from deceased organ donors that limits access to transplantation for many patients, about one of every seven kidneys (more than 1,500 each year) recovered from deceased donors in the United States are not transplanted. Eurotransplant, which coordinates organ distribution for six countries and a population of about 118 million, discards only one of every 20 kidneys procured for transplantation. We compared kidney procurement, transplants, and discards between January 2000 and June 2003 in the United States and in the Eurotransplant region using the Organ Procurement and Transplantation Network/United Network for Organ Sharing and Eurotransplant databases to examine differences that might account for this wide disparity.

Hormonal therapy of the brain-dead organ donor: experimental and clinical studies.

Experiments in Cape Town in the 1980s demonstrated that acute brain death is followed by massive catecholamine release resulting in systemic hypertension, acute left ventricular failure, and multiple cardiac arrhythmias along with substantial decreases in cortisol, insulin, thyroid, and antidiuretic hormone levels, a change from aerobic to anaerobic metabolism, and increases in inflammatory cytokines. Hormonal replacement results in rapid recovery of cardiac function in both experimental animals and humans and enables significantly more organs to be transplanted. Organ Procurement and Transplantation Network/United Network for Organ Sharing multivariate studies on hormonal treatment of brain-dead donors revealed significant increases in organs transplanted and in one-year survival of kidneys and hearts.

Aggressive pharmacologic donor management results in more transplanted organs.

BACKGROUND: Brain death results in adverse pathophysiologic effects in many cadaveric donors, resulting in cardiovascular instability and poor organ perfusion. Hormonal resuscitation (HR) has been reported to stabilize and improve cardiac function in brain-dead donors. The goal of this study was to examine the effect of HR on the brain-dead donor on the number of organs transplanted per donor. METHODS: A retrospective analysis of all brain-dead donors recovered in the United States from January 1, 2000, to September 30, 2001, was conducted. HR consisted of a methylprednisolone bolus and infusions of vasopressin and either triiodothyronine or L-thyroxine. Univariate analyses and multivariate logistic regression analyses were used to detect differences between the HR group and those donors who did not receive HR. RESULTS: Of 10,292 consecutive brain-dead donors analyzed, 701 received three-drug HR. Univariate analysis showed the mean number of organs from HR donors (3.8) was 22.5% greater than that from nonhormonal resuscitation donors (3.1) (P <0.001). Multivariate analyses showed that HR was associated with the following statistically significant increased probabilities of an organ being transplanted from a donor: kidney 7.3%, heart 4.7%, liver 4.9%, lung 2.8%, and pancreas 6.0%. Extrapolation of these probabilities to the 5,921 brain-dead donors recovered in 2001 was calculated to yield a total increase of 2,053 organs. CONCLUSION: HR stabilizes certain brain-dead donors and is associated with significant increases in organs transplanted per donor.

Hormonal resuscitation yields more transplanted hearts, with improved early function.

BACKGROUND: Brain death results in cardiovascular instability and poor organ perfusion in many brain-dead donors. Hormonal resuscitation stabilizes certain brain-dead donors and is associated with significant increases in the numbers of organs transplanted per donor. The goal of this study was to examine the quality of hearts recovered from donors treated with hormonal resuscitation. METHODS: A retrospective analysis of 4,543 recipients of hearts recovered from brain-dead donors, reported to the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between November 1, 1999, and December 31, 2001, was conducted. Hormonal resuscitation consisted of a methylprednisolone bolus and infusions of vasopressin and either triiodothyronine or l-thyroxine. Univariate and multivariate analyses were used to evaluate the quality of hearts from donors who received three-drug hormonal resuscitation (3HR) treatment versus donors who did not receive all three drugs (non-3HR). Death within 30 days and early graft dysfunction were used as endpoints. RESULTS: Hearts from 3HR donors demonstrated a 1-month survival rate of 96.2%, compared with a 92.1% survival rate for non-3HR donor hearts (P<0.01). Early graft dysfunction occurred in 5.6% of 3HR donor hearts and 11.6% of non-3HR donor hearts (P<0.01). Multivariate results demonstrated a 46% reduced odds of death within 30 days and a 48% reduced odds of early graft dysfunction. Steroids alone and steroids plus triiodothyronine/l-thyroxine also significantly reduced prolonged graft dysfunction. CONCLUSIONS: This study suggests that 3HR treatment of brain-dead donors results in increased numbers of transplanted hearts, with improved short-term graft function.

The role of procurement biopsies in acceptance decisions for kidneys retrieved for transplant.

BACKGROUND AND OBJECTIVES: There is a shortage of kidneys for transplant, and many patients on the deceased donor kidney transplant waiting list would likely benefit from kidneys that are currently being discarded. In the United States, the most common reason given for discarding kidneys retrieved for transplant is procurement biopsy results. This study aimed to compare biopsy results from discarded kidneys with discard attributed to biopsy findings, with biopsy results from comparable kidneys that were successfully transplanted. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective, observational, case-control study, biopsy reports were examined from 83 kidneys discarded in 2010 due to biopsy findings (cases), 83 contralateral transplanted kidneys from the same donor (contralateral controls), and 83 deceased donors randomly matched to cases by donor risk profile (randomly matched controls). A second procurement biopsy was obtained in 64 of 332 kidneys (19.3%). RESULTS: The quality of biopsy reports was low, with amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, and acute tubular necrosis often not indicated; 69% were wedge biopsies and 94% used frozen tissue. The correlation between first and second procurement biopsies was poor; only 25% of the variability (R(2)) in glomerulosclerosis was explained by biopsies being from the same kidney. The percentages of glomerulosclerosis overlapped substantially between cases, contralateral controls, and randomly matched controls: 17.1%±15.3%, 9.0%±6.6%, and 5.0%±5.9%, respectively. Of all biopsy findings, only glomerulosclerosis>20% was independently correlated with discard (cases versus contralateral controls; odds ratio, 15.09; 95% confidence interval, 2.47 to 92.41; P=0.003), suggesting that only this biopsy result was used in acceptance decisions. One-year graft survival was 79.5% and 90.7% in contralateral and randomly matched controls, respectively, versus 91.6% among all deceased donor transplants in the Scientific Registry of Transplant Recipients. CONCLUSIONS: Routine use of biopsies could lead to unnecessary kidney discards.

A review of studies relating to thyroid hormone therapy in brain-dead organ donors.

An acute decrease in cardiac performance can result from a reduced free triiodothyronine (FT3) level following (i) brain death (euthyroid sick syndrome), (ii) a period of cardiopulmonary bypass, and possibly (iii) regional or global myocardial ischemia. The two major pathophysiologic effects of brain death are (i) vascular injury associated with the hemodynamic consequences of the autonomic 'storm', and (ii) a generalized inhibition of mitochondrial function, which results in diminished organ function from the loss of energy stores from a rapid loss of circulating FT3. Deterioration of donor organ function can be reversed by hormonal replacement therapy, in which T3 plays a critical role. This results in (i) an increased number of organs being functionally acceptable, and (ii) increased early and intermediate graft survival. Cardiopulmonary bypass is associated with a reduction in the circulating level of FT3, and this can be associated with deterioration in cardiac function. The administration of T3 at the time of discontinuation of cardiopulmonary bypass reverses this state. In patients undergoing heart transplantation, T3 therapy to both donor and recipient is beneficial.

Organ donation in the United States: 1988-2003.

There were 6,457 deceased and 6,821 living donors recovered in 2003, a 58% and 274% increase over those recovered in 1988. The number of deceased donors aged 50 or older has increased from 12% of all donors in 1988 to 34% of all donors in 2003. The typical deceased donor in 2003 was a white male with ABO blood type O between the ages of 35-49. In 2003, a typical living donor was a white female with ABO blood type O between the ages of 35-49. Between 1988 and 2003, the percentage of minority donors increased for deceased donors (17% to 30%), and for living donors (24% to 30%). The number of living donors who were either spouses or unrelated to the recipient increased from 5% in 1988 to 33% in 2003. In 2003, California (10.2%) was most often listed as the state of residence for deceased donors, followed by Texas (7.9%) and Florida (6.9%). In 2003, deceased donors were recovered most often on Wednesdays (16.0%), followed by Tuesdays (15.2%) and Thursdays (14.7%). In 2003, living donors were recovered most often on Tuesdays (26.4%), followed by Wednesdays (25.5%) and Thursdays (20.7%). In 2003, deceased donors were recovered most often in October (9.0%), followed by January (8.6%), and July (8.6%). In 2003, living donors are recovered most often in July (10.2%), followed by October (8.9%) and June (8.6%).

Organ donation in the United States: 1988-2002.

1. There were 6,187 deceased and 6,618 living donors recovered in 2002, a 52% and 263% increase over those recovered in 1988. 2. The number of deceased donors aged 50 or older has increased from 12% of all donors in 1988 to 31% of all donors in 2002. 3. The typical deceased donor in 2002 was a White male with ABO blood type O between the ages of 18-34. In 2002, a typical living donor was a White female with ABO blood type O between the ages of 35-49. 4. Between 1988-2002, the percentage of minority donors increased among deceased donors (17% to 28%), and among living donors (24% to 29%). 5. The percentage of living donors who were either spouses or unrelated to the recipient increased from 5% in 1988 to 30% in 2002. 6. In 2002, California (10.2%) was most often listed as the state of residence for deceased donors, followed by Texas (7.9%) and Florida (6.7%). 7. In 2002, deceased donors were recovered most often on Tuesdays (15.7%), followed by Wednesdays (14.9%) and Thursdays (14.6%). 8. In 2002, living donors were recovered most often on Tuesdays (27.1%), followed by Wednesdays (26.8%) and Thursdays (20.3%). 9. In 2002, deceased donors were recovered most often in May (8.9%), followed by August (8.7%), and October (8.7%). 10. In 2002, living donors are recovered most often in July (10.0%), followed by June (9.0%) and May (8.8%).

Organ donation in the United States: 1988-2001.

Based upon information reported to the United Network for Organ Sharing (UNOS) as of December 12, 2002: 1. There were 6,082 cadaveric and 6,535 living donors recovered in 2001, a 49% and 258% increase over those recovered in 1988. 2. The number of cadaveric donors aged 50 or older increased from 12% of all donors in 1988 to 31% of all donors in 2001. 3. The typical cadaveric donor in 2001 was a white male with ABO blood type O between the ages of 35-49. In 2001, a typical living donor was a white female with ABO blood type O between the ages of 35-49. 4. Between 1988-2001, the percentage of minority donors increased for cadaveric donors (from 17% to 27%), and for living donors (from 24% to 30%). 5. The percentage of living donors who were either spouses or unrelated to the recipient increased from 5% in 1988 to 27% in 2001. 6. In 2001, California (10.2%) was most often listed as the state of residence for cadaveric donors, followed by Texas (7.9%) and Florida (7.2%). 7. In 2001, cadaveric donors were recovered most often on Tuesdays (15.1%), followed by Sundays (14.7%) and Mondays (14.6%). 8. In 2001, living donors were recovered most often on Wednesdays (28.7%), followed by Tuesdays (25.9%) and Thursdays (19.5%). 9. In 2001, cadaveric donors were recovered most often in October (9.2%), followed by May (9.0%), and August (8.8%). 10. In 2001, living donors were recovered most often in August (9.4%), followed by July (9.4%) and October (9.1%).

Benefit of child-to-parent kidney donation.

Use of child-to-parent (CTP) kidney donation may be limited because of ethical concerns as well as doubts about its effectiveness. We used the United Network for Organ Sharing database to examine the effectiveness of CTP kidney donation compared with other types of living-related (LD) kidney donation and to cadaveric kidney donation. Data from 56 873 kidney transplants performed between 1988 and 1998 showed significantly greater transplant and patient survival for CTP kidney transplants compared with cadaveric kidney transplants. The average gain in kidney transplant half-life is 3.6 years for a CTP compared with a cadaveric kidney transplant, and it is estimated that this gain for the recipient far outweighs the 1 in 3000 risk of death to the donor associated with kidney donation. We conclude that CTP kidney donation should not be discouraged, and represents a useful source of transplantable kidneys.