OPTN/SRTR 2018 Annual Data Report: Lung

The primary goal of US lung allocation policy is to ensure that candidates with the highest risk for mortality receive appropriate access to lung transplant. In 2018, 2562 lung transplants were performed in the US, reflecting a 31% increase over the past 5 years. More candidates are being listed for lung transplant, and the number of donors has increased substantially. Despite an increase of 84 lung transplants in 2018, 365 adult candidates died or became too sick to undergo transplant. In 2018, 24 new child (ages 0‐11 years) candidates were added to the lung transplant waiting list. Fifteen lung transplants were performed in recipients aged 0‐11 years, three in recipients aged younger than 1 year, two in recipients aged 1‐5 years, and ten in recipients aged 6‐11 years. Of 27 child candidates removed from the waiting list in 2018, 16 (59.3%) were removed due to undergoing transplant, six (22.2%) due to death, one (3.7%) due to improved condition, and one (3.7%) due to becoming too sick to undergo transplant.     

OPTN/SRTR 2019 Annual Data Report: Lung

The number of lung transplants performed continues to increase annually and reached an all-time high in 2019, with decreasing waitlist mortality. These trends are attributable to an increasing number of candidates listed for transplant each year and a continuing increase in the number of donors. Despite these favorable trends, 6.4% of lungs recovered for transplant were not transplanted in 2019, and strategies to optimize use of these available organs may reduce the number of waitlist even further. Time to transplant continued to decrease, as over 50% of candidates waited 3 months or less in 2019, yet regional heterogeneity remained despite policy changes intended to improve allocation equity. Small gains continued in posttransplant survival, with 1-year survival at 88.8%; 3 year, 74.4%; 5 year, 59.2%, and 10 year, 33.1 %.     

OPTN/SRTR 2017 Annual Data Report: Intestine

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).     

OPTN/SRTR 2018 Annual Data Report: Kidney

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.     

OPTN/SRTR 2019 Annual Data Report: Kidney

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.     

OPTN/SRTR 2017 Annual Data Report: Liver

Data on adult liver transplants performed in the US in 2017 are notable for (1) continued growth in numbers of new waitlist registrants (11,514) and of transplants performed (8,082); (2) continued increase in the transplant rate (51.5 per 100 waitlist‐years); (3) a precipitous decrease in waitlist registrations and transplants for hepatitis C‐related indications; (4) reciprocal increases in waitlist registrants and recipients with alcoholic liver disease and with clinical profiles consistent with non‐alcoholic fatty liver disease; and (5) continued improvement in graft survival despite changing recipient characteristics such as older age and higher rates of obesity. Variability in transplant rates remained by candidate race, presence of hepatocellular carcinoma, urgency status (status 1A versus model for end‐stage liver disease (MELD) score >35), and geography. More than half of all children listed for liver transplant in 2017 were aged younger than 5 years in 2017, and the highest rate of pretransplant mortality persisted for children aged younger than 1 year. Children underwent transplant at higher acuity than the past, as evidenced by higher MELD/pediatric end‐stage liver disease scores and listings at status 1A and 1B. Higher acuity at transplant is likely due to lack of access to suitable donor organs, which has been compensated for by persistent trends toward use of partial or split liver grafts and ABO‐incompatible grafts. Despite higher illness severity scores at transplant, pediatric graft and patient survival posttransplant have improved over time.     

Effects of broader geographic distribution of donor lungs on travel mode and estimated costs of organ procurement

On November 24, 2017, US lung transplant policy replaced donor service area with 250-nautical-mile radius as the first unit of allocation. Understanding this policy's economic impact is important, because the United States is poised to adopt the broadest feasible geographic organ distribution. All lung transplant recipients from January 1, 2015, to December 31, 2018, in the Scientific Registry of Transplant Recipients, were included. Recipients before and after November 24, 2017 were in the donor service area-first and 250-nautical-mile donor service area-free periods, respectively. Travel time was estimated using a Google application; mode was assigned as flying when driving time was longer than 60 min. Travel costs were estimated by mode and distance. Travel distance and time for organ procurement increased under the policy change. The estimated proportion of organs traveling by air increased from 61% to 76%. Estimated average costs increased by $14 051 if travel mode changed to flying, resulting in an average increase of $1264 for all transplants. Travel costs were highest for candidates <18 years and adults with high lung allocation scores. Broader geographic distribution increased estimated organ procurement costs for a small percentage of lung transplants. Further analysis should elucidate the broad economic impact of such policies.     

Lung Transplantation in Japan

The first successful living-donor lobar lung transplant (LDLLT) in Japan was performed at Okayama University in October 1998 after a long period of waiting for the legalization of thoracic organ transplantation. By May 2003, a further 41 lung transplants had been performed; 28 from living donors and 13 from cadaveric donors. The indications for a lung transplant are very specialized in Japan, the most common being primary pulmonary hypertension. Although the number of lung transplants is still small, survival in Japan, at 72% after 4 years, is better than the world average. Because the number of available cadaveric donors for lung transplantation is limited, at less than 5 per year, LDLLT is a realistic option for properly selected candidates.     

OPTN/SRTR 2018 Annual Data Report: Hepatitis C

Direct acting antivirals (DAAs) have fundamentally changed the treatment of hepatitis C virus (HCV) infection and reduced the discard rate of HCV‐infected organs by offering a treatment option with a high likelihood of cure posttransplant. This has spurred increased interest in transplanting organs from HCV‐positive donors into recipients both with and without HCV. In this chapter, we examine data from 2007 to 2018 to determine trends in HCV (+) donor transplants across various organ types. Since 2015, willingness to accept HCV (+) organs increased for candidates waitlisted for kidney, lung, heart, and pancreas transplant, but decreased for those listed for intestine transplant. For candidates listed for liver transplant, willingness to accept HCV (+) organs decreased from 2007 to 2017, but began increasing in 2017. Willingness to accept was not concentrated in a single US geographic area, and there was substantial variation among transplant programs and donation service areas. Numbers of anti‐HCV (+) donor kidney, heart, lung, and liver transplants have increased considerably in the past few years. Short‐term allograft survival for kidney and liver transplant recipients of anti‐HCV (+) organs appears to be comparable to that for recipients of anti‐HCV (‐) organs in an unadjusted analysis. However, an unadjusted analysis indicates that long‐term allograft survival may be worse. Kidney transplant between HCV‐infected donors and uninfected recipients with posttransplant DAA treatment is an emerging area. Short‐term data are promising, with similar 1‐year allograft survival compared with HCV‐uninfected donor to HCV‐uninfected recipient kidney transplants in unadjusted analyses. However, long‐term data are lacking and close monitoring in the future is warranted.     

Donor Age and Early Graft Failure After Lung Transplantation: A Cohort Study

Lungs from older adult organ donors are often unused because of concerns for increased mortality. We examined associations between donor age and transplant outcomes among 8860 adult lung transplant recipients using Organ Procurement and Transplantation Network and Lung Transplant Outcomes Group data. We used stratified Cox proportional hazard models and generalized linear mixed models to examine associations between donor age and both 1‐year graft failure and primary graft dysfunction (PGD). The rate of 1‐year graft failure was similar among recipients of lungs from donors age 18–64 years, but severely ill recipients (Lung Allocation Score [LAS] >47.7 or use of mechanical ventilation) of lungs from donors age 56–64 years had increased rates of 1‐year graft failure (p‐values for interaction = 0.04 and 0.02, respectively). Recipients of lungs from donors <18 and ≥65 years had increased rates of 1‐year graft failure (adjusted hazard ratio [HR] 1.23, 95% CI 1.01–1.50 and adjusted HR 2.15, 95% CI 1.47–3.15, respectively). Donor age was not associated with the risk of PGD. In summary, the use of lungs from donors age 56 to 64 years may be safe for adult candidates without a high LAS and the use of lungs from pediatric donors is associated with a small increase in early graft failure.     

Clinical judgment versus lung allocation score in predicting lung transplant waitlist mortality

Canadian lung transplant centers currently use a subjective and dichotomous “Status” ranking to prioritize waitlisted patients for lung transplantation. The lung allocation score (LAS) is an objective composite score derived from clinical parameters associated with both waitlist and post-transplant survival. We performed a retrospective cohort study to determine whether clinical judgment (Status) or LAS better predicted waitlist mortality. All adult patients listed for lung transplantation between 2007 and 2012 at three Canadian lung transplant programs were included. Status and LAS were compared in their ability to predict waitlist mortality using Cox proportional hazards models and C-statistics. Status and LAS were available for 1122 patients. Status 2 patients had a higher LAS compared to Status 1 patients (mean 40.8 (4.4) vs 34.6 (12.5), P = .0001). Higher LAS was associated with higher risk of waitlist mortality (HR 1.06 per unit LAS, 95% CI 1.05, 1.07, P < .001). LAS predicted waitlist mortality better than Status (C-statistic 0.689 vs 0.674). Patients classified as Status 2 and LAS ≥ 37 had the worst survival awaiting transplant, HR of 8.94 (95% CI 5.97, 13.37). LAS predicted waitlist mortality better than Status; however, the best predictor of waitlist mortality may be a combination of both LAS and clinical judgment.     

Lung and Heart Allocation in the United States

Lung and heart allocation in the United States has evolved over the past 20–30 years to better serve transplant candidates and improve organ utilization. The current lung allocation policy, based on the Lung Allocation Score, attempts to take into account risk of death on the waiting list and chance of survival posttransplant. This policy is flexible and can be adjusted to improve the predictive ability of the score. Similarly, in response to the changing clinical phenotype of heart transplant candidates, heart allocation policies have evolved to a multitiered algorithm that attempts to prioritize organs to the most infirm, a designation that fluctuates with trends in therapy. The Organ Procurement and Transplantation Network and its committees have been responsive, as demonstrated by recent modifications to pediatric heart allocation and mechanical circulatory support policies and by ongoing efforts to ensure that heart allocation policies are equitable and current. Here we examine the development of US lung and heart allocation policy, evaluate the application of the current policy on clinical practice and explore future directions for lung and heart allocation.     

Estimated impact of hepatitis C–positive lung donor utilization on US donor lung supply

The availability of highly effective direct‐acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection has led to reports of safely transplanting HCV⁺ donor lungs into HCV^? candidates. However, it remains unclear how the ability to use HCV⁺ donor lungs for lung transplant could affect the number of donor lungs available for transplant. Using Scientific Registry of Transplant Recipient data, we identified all deceased organ donors within the United States from March 1, 2015, to February 28, 2018, and stratified by HCV status. A donor prediction model for lung donation was derived and validated within HCV^? donors and applied to HCV⁺ donors to estimate the number of acceptable HCV⁺ lung donors. Of 29 481 eligible donors, 2054 (7.0%) were HCV⁺ donors with 82 HCV⁺ donors’ lungs being used for transplant during the study period. The prediction model for donor lung donation (specificity 92.6%, sensitivity 65.6%) estimated 248 HCV⁺ donors (75 nonviremic, 173 viremic) were acceptable for lung transplant during the study period, suggesting that 166 acceptable HCV⁺ lung donors were discarded. The ability to transplant lungs from HCV⁺ organ donors would lead to an estimated nationwide increase of at least 55 donor lungs per year, including 44 from HCV viremic donors.     

Should Pediatric Patients Wait for HLA‐DR‐Matched Renal Transplants?

Graft survival rates from deceased donors aged 35 years or less among all primary pediatric kidney transplant recipients in the United States between 1996 and 2004 were retrospectively examined to determine the effect of HLA‐DR mismatches on graft survival. Zero HLA‐DR‐mismatched kidneys had statistically comparable 5‐year graft survival (71%), to 1‐DR‐mismatched kidneys (69%) and 2‐DR‐mismatched kidneys (71%). When compared to donors less than 35 years of age, the relative rate of allograft failure was 1.32 (p = 0.0326) for donor age greater than or equal to age 35. There was no statistical increase in the odds of developing a panel‐reactive antibody (PRA) greater than 30% at the time of second waitlisting, based upon the degree of HLA‐A, ‐B or ‐DR mismatch of the first transplant, nor was there a ‘dose effect’ when more HLA antigens were mismatched between the donor and recipient. Therefore, pediatric transplant programs should utilize the recently implemented Organ Procurement and Transplantation Network's (OPTN) allocation policy, which prioritizes pediatric recipients to receive kidneys from deceased donors less than 35 years of age, and should not turn down such kidney offers to wait for a better HLA‐DR‐matched kidney.     

Lung Transplantation in the United States, 1998–2007

This article highlights trends and changes in lung and heart-lung transplantation in the United States from 1998 to 2007. The most significant change over the last decade was implementation of the Lung Allocation Score (LAS) allocation system in May 2005. Subsequently, the number of active wait-listed lung candidates declined 54% from pre-LAS (2004) levels to the end of 2007; there was also a reduction in median waiting time, from 792 days in 2004 to 141 days in 2007. The number of lung transplants performed yearly increased through the decade to a peak of 1 465 in 2007; the greatest single year increase occurred in 2005. Despite candidates with increasingly higher LAS scores being transplanted in the LAS era, recipient death rates have remained relatively stable since 2003 and better than in previous years. Idiopathic pulmonary fibrosis became the most common diagnosis group to receive a lung transplant in 2007 while emphysema was the most common diagnosis in previous years. The number of retransplants and transplants in those aged ≥65 performed yearly have increased significantly since 1998, up 295% and 643%, respectively. A decreasing percentage of lung transplant recipients are children (3.5% in 2007, n = 51). With LAS refinement ongoing, monitoring of future impact is warranted.     

Process of selecting and educating HCV‐uninfected kidney waiting‐list candidates for HCV‐infected kidney transplantation

Long waiting times for kidney transplant (KT) and the high risk of mortality on dialysis have prompted investigation into strategies to utilize hepatitis C virus (HCV)‐infected organs to decrease discard rates of potentially viable kidneys. Due the opioid epidemic, the number of HCV‐infected donors has increased significantly. With the development of direct‐acting antiviral therapies for HCV infection, now more than 95% of patients who received treatment are cured. Experimental trials have used direct‐acting antiviral therapy to treat HCV infection in HCV‐uninfected transplant recipients of kidneys from HCV‐viremic donors. To date, HCV has been eradicated in all cases. Though these strategies will potentially increase the donor pool of available kidneys, shorten waitlist times, and ultimately decrease mortality in patients waiting for KT, identifying the ideal candidates and educating them about a protocol to utilize direct‐acting antiviral therapy to cure HCV after it is transmitted is essential. We present our approach to patient selection and education for a clinical trial in transplantation of HCV viremic kidneys into uninfected recipients.     

Preliminary Marked Increase in the National Organ Donation Rate in Israel Following Implementation of a New Organ Transplantation Law

Israel's organ donation rate has always been among the lowest in Western countries. In 2008 two new laws relevant to organ transplantation were introduced. The Brain‐Respiratory Death Law defines the precise circumstances and mechanisms to determine brain death. The Organ Transplantation Law bans reimbursing transplant tourism involving organ trade, grants prioritization in organ allocation to candidates who are registered donors and removes disincentives for living donation by providing modest insurance reimbursement and social supportive services. The preliminary impact of the gradual introduction and implementation of these laws has been witnessed in 2011. Compared to previous years, in 2011 there was a significant increase in the number of deceased organ donors directly related to an increase in organ donation rate (from 7.8 to 11.4 donors per million population), in parallel to a significant increase in the number of new registered donors. In addition the number of kidney transplantations from living donors significantly increased in parallel to a significant decrease in the number of kidney transplantations performed abroad (from 155 in 2006 to 35 in 2011). The new laws have significantly increased both deceased and living organ donation while sharply decreasing transplant tourism.     

Broader Geographic Sharing of Pediatric Donor Lungs Improves Pediatric Access to Transplant

US pediatric transplant candidates have limited access to lung transplant due to the small number of donors within current geographic boundaries, leading to assertions that the current lung allocation system does not adequately serve pediatric patients. We hypothesized that broader geographic sharing of pediatric (adolescent, 12–17 years; child, <12 years) donor lungs would increase pediatric candidate access to transplant. We used the thoracic simulated allocation model to simulate broader geographic sharing. Simulation 1 used current allocation rules. Simulation 2 offered adolescent donor lungs across a wider geographic area to adolescents. Simulation 3 offered child donor lungs across a wider geographic area to adolescents. Simulation 4 combined simulations 2 and 3. Simulation 5 prioritized adolescent donor lungs to children across a wider geographic area. Simulation 4 resulted in 461 adolescent transplants per 100 patient‐years on the waiting list (range 417–542), compared with 206 (range 180–228) under current rules. Simulation 5 resulted in 388 adolescent transplants per 100 patient‐years on the waiting list (range 348–418) and likely increased transplant rates for children. Adult transplant rates, waitlist mortality, and 1‐year posttransplant mortality were not adversely affected. Broader geographic sharing of pediatric donor lungs may increase pediatric candidate access to lung transplant.     

Allowing HIV‐Positive Organ Donation: Ethical,Legal and Operational Considerations

Case reports of kidney transplantation using HIV‐positive (HIV+) donors in South Africa and advances in the clinical care of HIV+ transplant recipients have drawn attention to the legal prohibition of transplanting organs from HIV+ donors in the United States. For HIV+ transplant candidates, who face high barriers to transplant access, this prohibition violates beneficence by placing an unjustified limitation on the organ supply. However, transplanting HIV+ organs raises nonmaleficence concerns given limited data on recipient outcomes. Informed consent and careful monitoring of outcome data should mitigate these concerns, even in the rare circumstance when an HIV+ organ is intentionally transplanted into an HIV‐negative recipient. For potential donors, the federal ban on transplanting HIV+ organs raises justice concerns. While in practice there are a number of medical criteria that preclude organ donation, only HIV+ status is singled out as a mandated exclusion to donation under the National Organ Transplant Act (NOTA). Operational objections could be addressed by adapting existing approaches used for organ donors with hepatitis. Center‐specific outcomes should be adjusted for HIV donor and recipient status. In summary, transplant professionals should advocate for eliminating the ban on HIV+ organ donation and funding studies to determine outcomes after transplantation of these organs.     

Geographic disparities in lung transplant rates

In November 2017, in response to a lawsuit from a New York City lung transplant candidate, an emergency change to the lung allocation policy eliminated the donation service area (DSA) as the first geographic tier of allocation. The lawsuit claimed that DSA borders are arbitrary and that allocation should be based on medical priority. We investigated whether deceased‐donor lung transplant (LT) rates differed substantially between DSAs in the United States before the policy change. We estimated LT rates per active person‐year using multilevel Poisson regression and empirical Bayes methods. We found that the median incidence rate ratio (MIRR) of transplant rates between DSAs was 2.05, meaning a candidate could be expected to double their LT rate by changing their DSA. This can be compared directly to a 1.54‐fold increase in LT rate that we found associated with an increase in lung allocation score (LAS) category from 38‐42 to 42‐50. Changing a candidate's DSA would have had a greater impact on the candidate's LT rate than changing LAS categories from 38‐42 to 42‐50. In summary, we found that the DSA of listing was a major determinant of LT rate for candidates across the country before the emergency lung allocation change.