Kidney,Pancreas and Liver Allocation and Distribution in the United States

Kidney transplant and liver transplant are the treatments of choice for patients with end‐stage renal disease and end‐stage liver disease, respectively. Pancreas transplant is most commonly performed along with kidney transplant in diabetic end‐stage renal disease patients. Despite a steady increase in the numbers of kidney and liver transplants performed each year in the United States, a significant shortage of kidneys and livers available for transplant remains. Organ allocation is the process the Organ Procurement and Transplantation Network (OPTN) uses to determine which candidates are offered which deceased donor organs. OPTN is charged with ensuring the effectiveness, efficiency and equity of organ sharing in the national system of organ allocation. The policy has changed incrementally over time in efforts to optimize allocation to meet these often competing goals. This review describes the history, current status and future direction of policies regarding the allocation of abdominal organs for transplant, namely the kidney, liver and pancreas, in the United States.     

Development of the New Lung Allocation System in the United States

This article reviews the development of the new U.S. lung allocation system that took effect in spring 2005. In 1998, the Health Resources and Services Administration of the U.S. Department of Health and Human Services published the Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule, which became effective in 2000, the OPTN had to demonstrate that existing allocation policies met certain conditions or change the policies to meet a range of criteria, including broader geographic sharing of organs, reducing the use of waiting time as an allocation criterion and creating equitable organ allocation systems using objective medical criteria and medical urgency to allocate donor organs for transplant. This mandate resulted in reviews of all organ allocation policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN Thoracic Organ Transplantation Committee. This paper reviews the deliberations of the Subcommittee in identifying priorities for a new lung allocation system, the analyses undertaken by the OPTN and the Scientific Registry for Transplant Recipients and the evolution of a new lung allocation system that ranks candidates for lungs based on a Lung Allocation Score, incorporating waiting list and posttransplant survival probabilities.     

Racial and Ethnic Differences in Mortality in Children Awaiting Heart Transplant in the United States

Racial differences in outcomes are well known in children after heart transplant (HT) but not in children awaiting HT. We assessed racial and ethnic differences in wait‐list mortality in children <18 years old listed for primary HT in the United States during 1999–2006 using multivariable Cox models. Of 3299 listed children, 58% were listed as white, 20% as black, 16% as Hispanic, 3% as Asian and 3% were defined as ‘Other’. Mortality on the wait‐list was 14%, 19%, 21%, 17% and 27% for white, black, Hispanic, Asian and Other children, respectively. Black (hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.3, 1.9), Hispanic (HR 1.5, CI 1.2, 1.9), Asian (HR, 2.0, CI 1.3, 3.3) and Other children (HR 2.3, CI 1.5, 3.4) were all at higher risk of wait‐list death compared to white children after controlling for age, listing status, cardiac diagnosis, hemodyamic support, renal function and blood group. After adjusting additionally for medical insurance and area household income, the risk remained higher for all minorities. We conclude that minority children listed for HT have significantly higher wait‐list mortality compared to white children. Socioeconomic variables appear to explain a small fraction of this increased risk.     

Lung allocation score: the Eurotransplant model versus the revised US model – a cross‐sectional study

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine‐tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty‐three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET.     

Organ allocation in pediatric transplantation in France

In France, ministerial decrees in 1995 and 1996 gave children under 16 who are awaiting transplantation national priority for kidneys and livers from donors under 16, and regional priority for kidneys and livers from donors under 30. We analyzed the effects of these changes on waiting time, death on the waiting list, and balance between demand and supply. The percentage of children who received a transplant during the year of registration increased from 40% in 1993 to 67% in 1998 for kidney transplantation, but only from 50% to 67% for liver transplantation. The number of new children registered on the renal transplant waiting list (84 in 1998) and the number transplanted (85 in 1998) are balanced. But, because of the number of children still on the waiting list at the end of each year, there remains an imbalance of about 70 for kidney transplantation. For liver transplantation, there remains an imbalance of about 35. Death on the renal transplant waiting list has been below 2% since 1993. Death on the liver transplant waiting list decreased from 10–20% in 1993–1995 to 3% in 1998. The number of children who died on the thoracic organ waiting list in 1998 was the same as the number transplanted. In conclusion, the new rules governing organ allocation to children in France have shortened waiting time for renal transplantation, but not for liver transplantation. Many children still die on the waiting list for thoracic organ transplantation. Received: 4 July 2001 / Revised: 4 October 2001 / Accepted: 4 October 2001     

Simulated Regionalization of Heart and Lung Transplantation in the United States

We simulated the impact of regionalization of isolated heart and lung transplantation within United Network for Organ Sharing (UNOS) regions. Overall, 12 594 orthotopic heart transplantation (OHT) patients across 135 centers and 12 300 orthotopic lung transplantation (OLT) patients across 67 centers were included in the study. An algorithm was constructed that “closed” the lowest volume center in a region and referred its patients to the highest volume center. In the unadjusted analysis, referred patients were assigned the highest volume center's 1‐year mortality rate, and the difference in deaths per region before and after closure was computed. An adjusted analysis was performed using multivariable logistic regression using recipient and donor variables. The primary outcome was the potential number of lives saved at 1 year after transplant. In adjusted OHT analysis, 10 lives were saved (95% confidence interval [CI] 9–11) after one center closure and 240 lives were saved (95% CI 209–272) after up to five center closures per region, with the latter resulting in 1624 total patient referrals (13.2% of OHT patients). For OLT, lives saved ranged from 29 (95% CI 26–32) after one center closure per region to 240 (95% CI 224–256) after up to five regional closures, but the latter resulted in 2999 referrals (24.4% of OLT patients). Increased referral distances would severely limit access to care for rural and resource‐limited populations.     

Increasing Lung Allocation Scores Predict Worsened Survival Among Lung Transplant Recipients

Implemented in 2005, the lung allocation score (LAS) aims to distribute donor organs based on overall survival benefits for all potential recipients, rather than on waiting list time accrued. While prior work has shown that patients with scores greater than 46 are at increased risk of death, it is not known whether that risk is equivalent among such patients when stratified by LAS score and diagnosis. We retrospectively evaluated 5331 adult lung transplant recipients from May 2005 to February 2009 to determine the association of LAS (groups based on scores of ≤46, 47–59, 60–79 and ≥80) and posttransplant survival. When compared with patients with LAS ≤ 46, only those with LAS ≥ 60 had an increased risk of death (LAS 60–79: hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.21–1.90; LAS ≥ 80: HR, 2.03; CI, 1.61–2.55; p < 0.001) despite shorter median waiting list times. This risk persisted after adjusting for age, diagnosis, transplant center volume and donor characteristics. By specific diagnosis, an increased hazard was observed in patients with COPD with LAS ≥ 80, as well as those with IPF with LAS ≥ 60.     

High Emergency Lung Transplantation: dramatic decrease of waiting list death rate without relevant higher post‐transplant mortality

Many candidates for lung transplantation (LT) die on the waiting list, raising the question of graft availability and strategy for organ allocation. We report the experience of the new organ allocation program, “High Emergency Lung Transplantation” (HELT), since its implementation in our center in 2007. Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT from 1st July 2007 to 31th May 2012. HELT candidates had a higher impairment grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients had increased incidence of perioperative complications (e.g., perioperative bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, P = 0.0005). No significant difference was observed between HELT and non‐HELT patients in mechanical ventilation duration (15.5 days vs. 11 days, P = 0.27), intensive care unit length of stay (15 days vs. 10 days, P = 0.22) or survival rate at 12 (81% vs. 80%), and 24 months post‐LT (72.9% vs. 75.0%). Lastly, mortality on the waiting list was spectacularly reduced from 19% to 2% when compared to the non‐HELT 2004–2007 group. Despite a more severe clinical status of patients on the waiting list, HELT provided similar results to conventional LT. These results were associated with a dramatic reduction in the mortality rate of patients on the waiting list.     

Thoracic Organ Transplantation in the United States, 1995–2004

This article reviews trends in thoracic organ transplantation based on OPTN/SRTR data from 1995 to 2004. The number of active waiting list patients for heart transplants continues to decline, primarily because there are fewer patients with coronary artery disease listed for transplantation. Waiting times for heart transplantation have decreased, and waiting list deaths also have declined, from 259 per 1000 patient-years at risk in 1995 to 156 in 2004. Fewer heart transplants were performed in 2004 than in 1995, but adjusted patient survival increased to 88% at 1 year and 73% at 5 years. Emphysema, idiopathic pulmonary fibrosis and cystic fibrosis were the most common indications among lung transplant recipients in 2004. Waiting time for lung transplantation decreased between 1999 and 2004. Waiting list mortality decreased to 134 per 1000 patient-years at risk in 2004. One-year survival following transplantation has improved significantly in the past decade. The number of combined heart-lung transplants performed in the United States remains low, with only 39 performed in 2004. Overall unadjusted survival, at 58% at 1 year and 40% at 5 years, is lower among heart-lung recipients than among either heart or lung recipients alone.     

Thoracic organ transplantation in the United States, 1994–2003

Using OPTN/SRTR data, this article reviews the state of thoracic organ transplantation in 2003 and the previous decade. Time spent on the heart waiting list has increased significantly over the last decade. The percentage of patients awaiting heart transplantation for >2 years increased from 23% in 1994 to 49% by 2003. However, there has been a general decline in heart waiting list death rates over the decade. In 2003, the lung transplant waiting list reached a record high of 3,836 registrants, up slightly from 2002 and more than threefold since 1994. One-year patient survival for those receiving lungs in 2002 was 82%, a statistically significant improvement from 2001 (78%). The number of patients awaiting a heart-lung transplant, declining since 1998, reached 189 in 2003. Adjusted patient survival for heart-lung recipients is consistently worse than the corresponding rate for isolated lung recipients, primarily due to worse outcomes for heart-lung recipients with congenital heart disease. A new lung allocation system, approved in June 2004, derives from the survival benefit of transplantation with consideration of urgency based on waiting list survival, instead of being based solely on waiting time. A goal of the policy is to minimize deaths on the waiting list.     

Unintended Consequences of the New National Kidney Allocation Policy in the United States

The new national Kidney Allocation System of the Organ Procurement and Transplantation Network (OPTN), effective as of December 4, 2014, was designed to improve the chances of transplanting the most highly sensitized patients on the waitlist, those with calculated panel reactive antibody values of 98%, 99% and 100%. Recently, it was suggested that these highly sensitized patients will experience inequitable access, given the reported high prevalence of antibodies to HLA‐DP, and the fact that only about 1/3 of deceased donors are typed for HLA‐DP antigens. Here we report that 320/2948 flow cytometric crossmatches performed for the Northwestern transplant program over the past 28 months were positive solely due to HLA‐DP donor‐specific antibodies (11%; 16.5% of patients with HLA antibodies—sensitized patients). We further show that 58/207 (12%) HLA‐DR serologically matched donor‐recipient pairs had a positive B cell flow crossmatch due to donor‐specific HLA class II antibodies, and 2/34 (6%) serologic zero‐HLA‐A‐B‐DR mismatch had a positive flow crossmatch due to HLA‐DSA. We therefore provide information regarding the necessity and importance of complete donor HLA typing including both chains of the HLA‐DP antigen (encoded by HLA‐DPA1 and HLA‐DPB1) at the time of organ offer.     

Lung transplantation in the Lung Allocation Score era: Medium‐term analysis from a single center

In 2005, the Lung Allocation Score (LAS) was implemented as the allocation system for lungs in the US. We sought to compare 5‐year lung transplant outcomes before and after the institution of the LAS. Between 2000 and 2011, 501 adult patients were identified, with 132 from January 2000 to April 2005 (Pre‐LAS era) and 369 from May 2005 to December 2011 (Post‐LAS era). Kruskal‐Wallis or chi‐squared test was used to determine significance between groups. Survival was censored at 5 years. Overall, the post‐LAS era was associated with more restrictive lung disease, higher LAS scores, shorter wait‐list times, more preoperative immunosuppression, and more single lung transplantation. In addition, post‐LAS patients had higher O₂ requirements with greater preoperative pulmonary impairment. Postoperatively, 30‐day mortality improved in post‐LAS era (1.6% vs 5.3%, P = .048). During the pre‐ and post‐LAS eras, 5‐year survival was 52.3% and 55.3%, respectively (P = .414). The adjusted risk of mortality was not different in the post‐LAS era (P = .139). Freedom from chronic lung allograft dysfunction was significantly higher in the post‐LAS era (P = .002). In this single‐center report, implementation of the LAS score has led to allocation to sicker patients without decrement in short‐ or medium‐term outcomes. Freedom from CLAD at 5 years is improving after LAS implementation.     

Heart and Lung Transplantation in the United States, 1997–2006

This article highlights trends in heart and lung transplantation between 1997 and 2006, drawing on data from the OPTN and SRTR. The total number of candidates actively awaiting heart transplantation declined by 45% over the last decade, dropping from 2414 patients in 1997 to 1327 patients in 2006. The overall death rates among patients awaiting heart transplantation declined over the same period. The distribution of recipients among the different status groups at the time of heart transplantation changed little between the inception of the new classification system in 1999 and 2005. Deaths in the first year after heart transplantation have steadily decreased. At the end of 2006, 2885 candidates were awaiting a lung transplant, up 10% from the 1997 count. The median time-to-transplant for listed patients decreased by 87% over the decade, dropping from 1053 days in 1997 to 132 days in 2006. Selection for listing and transplantation has shifted toward more urgent patients since the May 2005 implementation of a new lung allocation system based on survival benefit and urgency rather than waiting time. Only 31 heart-lung transplants were performed in 2006, down from a high of 62 in 1997.