United Network Of Organ Sharing Research Articles

Editorial introductions

Editorial introductions

Tu1564 – Predictors of Outcome and Rate of Graft Failure in Patients with Primary Sclerosing Cholangitis Due to Inflammatory Bowel Disease After Receiving Liver Transplant. A Descriptive Study from the United Network of Organ Sharing (UNOS) Database

Tu1564 – Predictors of Outcome and Rate of Graft Failure in Patients with Primary Sclerosing Cholangitis Due to Inflammatory Bowel Disease After Receiving Liver Transplant. A Descriptive Study from the United Network of Organ Sharing (UNOS) Database

Development and future deployment of a 5 years allograft survival model for kidney transplantation.

Identifying kidney transplant patients at highest risk for graft loss prior to loss may allow for effective interventions to improve 5 years survival. We performed a 10 years retrospective cohort study of adult kidney transplant recipients (n = 1747). We acquired data from electronic health records, United Network of Organ Sharing, social determinants of health, natural language processing data extraction, and real-time capture of dynamically evolving clinical data obtained within 1 year of transplant; from which we developed a 5 years graft survival model. Total of 1439 met eligibility; 265 (18.4%) of them experienced graft loss by 5 years. Graft loss patients were characterized by: older age, being African-American, diabetic, unemployed, smokers, having marginal donor kidneys and cardiovascular comorbidities. Predictive dynamic variables included: low mean blood pressure, higher pulse pressures, higher heart rate, anaemia, lower estimated glomerular filtration rate peak, increased tacrolimus variability, rejection and readmissions. This Big Data analysis generated a 5 years graft loss model with an 82% predictive capacity, versus 66% using baseline United Network of Organ Sharing data alone. Our analysis yielded a 5 years graft loss model demonstrating superior predictive capacity compared with United Network of Organ Sharing data alone, allowing post-transplant individualized risk-assessed care prior to transitioning back to community care.

Does the Canadian allocation system for highly sensitized patients work?

The number of sensitized heart transplant candidates is rising. Highly sensitized patients are disadvantaged because they encounter longer waiting times to heart transplant. Strategies to reduce their waiting times include waitlist prioritization and desensitization therapies. The purpose of this review is to describe the listing category for highly sensitized patients in the Canadian allocation system, examine the advantages and limitations of this strategy and provide an approach to the management of the highly sensitized patient awaiting heart transplant. Analysis of data from the United Network of Organ Sharing shows that the incidence of death or removal from the waitlist in patients listed for heart transplant increases as the calculated panel reactive antibody (cPRA) increases and is independent of medical urgency. In the Canadian allocation system, patients with cPRA more than 80% have a similar incidence of death on the waitlist as less sensitized patients, suggesting they survive to be transplanted. Furthermore, prioritizing and transplanting highly sensitized patients has been associated with acceptable post-transplant outcomes. The Canadian allocation system prioritizes highly sensitized patients to increase equity and access to transplantation while maintaining good post-transplant outcomes. Not all highly sensitized patients can wait for an organ, even if prioritized. A pragmatic individualized approach would consider the medical stability of the patient, the likelihood of transplant with a negative crossmatch and then determine whether waitlist prioritization or desensitization is the more appropriate strategy.

Liver Allocation Policies in the USA: Past, Present, and the Future.

Identifying the optimal allocation policy with regard to hepatocellular carcinoma has been a persistent and evolving challenge. The current criteria for LT for HCC endorsed by the United Network of Organ Sharing (UNOS) are based on the Milan Criteria: a solitary tumor <5cm, or maximum of three tumors ≤3cm each, without vascular invasion or evidence of extrahepatic spread. Contraindications to HCC exception points include: stage 1 HCC, ruptured HCC, extrahepatic HCC, and main portal or hepatic vein HCC invasion. Based upon projected waitlist dropout rates due to tumor growth, patients with HCC are assigned MELD standardized exception points. In addition to tumor size and number, AFP levels are an important predictor of recurrence of HCC following liver transplantation. Standardized exception points for HCC patients are not awarded to patients with AFP levels >1000ng/mL that do not decrease to < 500 ng/mL with treatment. Appeals for MELD exception points for patients with HCC vary widely between UNOS regions, with success of nonstandardized exception point appeals varying from 3.1 to 21% between regions. In an effort to make prioritization for HCC more consistent, a national liver review board (NLRB)is being convened that will focus on developing a national guidance for assessing common requests and addressing exception points, including for HCC.

Impact of Center Volume on Post Heart Transplant Survival

Purpose Previous studies have shown reduced 1-year post-transplant survival in low volume centers. We aimed to evaluate impact of center volume on post heart transplant survival in recent era of streamlined care. Methods The United Network of Organ Sharing (UNOS) database was queried for patients aged ≥ 18 years undergoing heart transplant between 2007-2016. The database was then merged to 2010 US census data and CDC 2015 heart failure mortality data. Center volume was available in encrypted center codes and divided in terciles ( 22-high) after removing centers that did not transplant organs since 2014. The available data was then evaluated with a cox-regression model to identify impact of center volume, UNOS regions, adjusting for individual patient level factors. Kaplan-Meier curves were computed to evaluate survival differences in center volume by UNOS regions. Results There were 111 centers included in the final dataset. There were 23 low, 52 medium and 36 high volume centers that performed 1084 (5%), 7995 (35%) and 13520 (60%) heart transplants respectively. Low volume centers had equivalent survival to medium and high volume centers across all UNOS regions except region 10 (Figure 1). A cox-regression model adjusting for recipient and donor factors showed that high volume centers in regions 2 (HR=0.79 (0.67-0.94)), 4 (HR=0.65 (0.46-0.92)) and 10 (HR=0.44 (0.30-0.63)) had significantly better survival whereas in region 8 they had worse survival (HR=2.0 (1.2-3.4))(Figure 2). Conclusion Post heart transplant survival at low and medium volume centers across all UNOS regions is comparable to high volume centers except in regions 2, 4 and 10.

Impact of Donor-Recipient Sex Mismatch on the Incidence of Allograft Rejection in Clinical Lung Transplantation: A Review of the United Network of Organ Sharing Database

Purpose It is well-known that female animals mount immune responses against male-specific antigens, thought to be principally derived from proteins whose genes are Y chromosome-encoded. Although organ transplantation frequently involves donor-recipient sex mismatch, the immunological sequelae of such mismatches, particularly from male donor organs transplanted into female recipients, are unclear. Methods A review of the United Network of Organ Sharing (UNOS) database was conducted from 10/1987 to 12/2016. Recipient and graft survivals, and the incidences of acute rejection (AR)-related hospitalization and bronchiolitis obliterans syndrome (BOS), were determined across four groups: male donor-male recipient (dMrM, n = 12095), female donor-female recipient (dFrF, n=7444), female donor-male recipient (dFrM, n=3962) and male donor-female recipient (dMrF, n = 5766). Results AR-related hospitalization was specifically increased only in the dMrF group (p=0.006). In addition, severe BOS (Grade 3) was specifically increased only in the dMrF group (p Conclusion In clinical lung transplantation, female recipients of male allografts specifically exhibited significantly increased rates of AR and BOS. These findings are consistent with well-established immunological concepts and evidence, and have implications for donor-recipient matching in order to achieve optimal outcomes.

Disparities in Utilization of Hepatitis C Virus Positive Hearts for Transplantation

Purpose The goal of this study was to utilize data from the United Network of Organ Sharing (UNOS) database to assess disparities in utilization of hepatitis C virus (HCV)+ hearts for transplant. Methods We obtained de-identified data from UNOS from 2/1/16-1/31/18. We divided these donors into three categories: HCV -, HCV antibody+/ nucleic acid test negative (HCV+/ NAT-) and HCV NAT+. Utilization rate was calculated as a percentage of number of hearts successfully transplanted / number of donors recovered. Organ quality was indirectly assessed using donor age and ejection fraction (EF). Differences in means were assessed via ANOVA and categorical variables via chi2 analysis. Results Among 20,442 donors, 18,948 were HCV-, 511 were HCV+ NAT- and 983 were HCV NAT+. The overall mean utilization rate of HCV- hearts was 33.7% (standard deviation, SD 1.74) whereas the HCV+/NAT- was 11.6% (SD 7.15) and NAT+ was 7.1% (SD 4.94, p organ procurement organizations (OPOs) out of 5 in the Region that facilitated 73% of donors. Proportion of transplanted hearts with EF>55% was similar (HCV- 93.1% vs. HCV+/NAT- 89.8% vs. NAT+ 97.3%, p=0.73). Proportion of transplanted hearts with donor age Conclusion We note disparities at a national, regional, and OPO level in the utilization of hearts for transplantation based on HCV status. Given early outcomes of HCV+ heart transplant , we believe there is opportunity to increase heart transplantation rates in the US.

The Impact of the Calculated Panel Reactive Antibody Value on Wait List Outcomes for Lung Transplant Candidates

Purpose We conducted a retrospective cohort study using United Network of Organ Sharing (UNOS) data to determine the impact of the calculated panel reactive antibody (cPRA) value on wait list outcomes for lung transplant candidates. Methods A dataset of candidates listed for lung transplant from 2005-2017 was obtained from UNOS. We divided the candidates into groups based on their cPRA value at the time of wait list activation (0-25%, 25.1-50%, 50.1-75%, 75.1-100%) and compared each group to the lowest quartile (or minimally sensitized, MS) group using a competing risk regression model. The primary outcome was lung transplant. The secondary outcome was death/delisting for clinical deterioration. Results Figure 1 shows the frequency of wait list outcomes by cPRA value at the time of wait list activation. Candidates with a cPRA value of 25.1-50% at the time of wait list activation did not have a significantly different likelihood of lung transplant or death/delisting for clinical deterioration than the MS group. Candidates with a cPRA value of 50.1-75% were 25% less likely to undergo lung transplant and were 44% more likely to die/be delisted for clinical deterioration than the MS group. Candidates with a cPRA value of 75.1-100% were 52% less likely to undergo lung transplant and were 92% more likely to die/be delisted for clinical deterioration than the MS group. Figure 2 shows the cumulative incidence of lung transplant (A) and death/delisting for clinical deterioration (B) by cPRA value. Conclusion CPRA values of greater than 50% are associated with a significantly lower rate of lung transplant and higher wait list mortality.

Burden of excess mortality after implementation of the new kidney allocation system may be borne disproportionately by middle-aged recipients.

Under the new kidney allocation system (KAS), implemented in 2014, the distribution of the best quality donor kidney grafts shifted between age groups, but it is unclear whether this change translates to meaningful differences in post-transplant outcomes. We conducted a retrospective cohort study of 20,345 deceased donor kidney transplant recipients before and 4,605 recipients after implementation of the KAS using data from the United Network of Organ Sharing. Overall, two-year mortality was greater among recipients in the post-KAS era compared with the pre-KAS era (6.31% vs 5.91% respectively, [p = 0.01]), and two-year graft loss was not significantly different between eras (9.95% and 9.65%, respectively [p = 0.13]). In analysis stratified by age group (18–45, 46–55, 56–65, and ≥66 years), relative risk of mortality was 1.48 (95% confidence interval [CI] 1.09–1.98) among recipients 46–55 years old and 1.47 (95% CI 1.18–1.81) among recipients 56–65 years old. Relative risk of all-cause graft loss was 1.43 (95% CI 1.20–1.70) among recipients 56–65 years old. There were no significant differences in relative risk of mortality or graft loss associated with the KAS era among other age groups. After adjustment for recipient characteristics and characteristics of the changing donor pool, relative risk of two-year mortality and graft loss associated with the post-KAS era was attenuated for recipients aged 46–55 and 56–65 years, but remained statistically significant. In this early analysis after implementation of the KAS, there is suggestion that increased risk of mortality and graft loss may be disproportionately borne by middle-aged recipients, which is only partially accounted for by changes in recipient and donor characteristics. These findings signal a need to continue to monitor the effects of the KAS to ensure that allocation practices both maximize utility of the kidney graft pool and respect fairness between age groups.

Reducing stigmatizing attitudes towards mental illness among medical students

The use of left ventricular assist devices (LVADs) as a bridge to heart transplantation has increased rapidly over the last 2 decades. We aim to explore the effect of pretransplant systemic and device-related complications on posttransplant survival for patients bridged with LVADs.The United Network of Organ Sharing (Organ Procurement and Transplantation Network) database was queried for all adult heart transplant recipients (aged ≥ 18 y) transplanted from April 1, 2015, to June 31, 2018. Device-related complications included thrombosis, device infection, device malfunction, life-threatening arrhythmia, and other device complications. Systemic complications included a new dialysis need or ventilator dependence between the time of listing and transplantation, transfusion, or systemic infection requiring treatment with intravenous antibiotics within 2 wk of transplantation.A total of 2131 patients were identified as requiring LVAD support before transplantation. LVAD patients had high rates of preoperative systemic complications (53%) and high rates of device-related complications (42.7% experienced at least one device-related complication). Kaplan–Meier analysis revealed a significantly decreased 1-y survival for LVAD patients bridged to transplantation who experienced a pretransplant systemic complication (P = 0.041). Interestingly, preoperative device-related complications had no effect on 1-y posttransplantation survival (P = 0.93). Multivariate Cox modeling revealed that systemic complications were associated with a significantly increased risk of posttransplant mortality for LVAD patients (hazard ratio 1.45; P = 0.033).Recipients who suffered a systemic complication while awaiting heart transplantation experienced higher short-term mortality rates. Device-related complications do not appear to impact posttransplantation outcomes.

Reliability of deceased-donor procurement kidney biopsy images uploaded in United Network for Organ Sharing.

Prior studies demonstrate poor agreement among pathologists' interpretation of kidney biopsy slides. Reliability of representative images of these slides uploaded to the United Network of Organ Sharing (UNOS) web portal for clinician review has not been studied. We hypothesized high agreement among pathologists' image interpretation, since static images eliminate variation induced by viewing different areas of movable slides. To test our hypothesis, we compared the assessments of UNOS-uploaded images recorded in standardized forms by three pathologists. We selected 100 image sets, each having at least two images from kidneys of deceased donors. Weighted Cohen's kappa was used for inter-rater agreement. Mean (SD) donor age was 50 (13). Acute tubular injury had kappas of 0.12, 0.14, and 0.19; arteriolar hyalinosis 0.16, 0.27, and 0.38; interstitial inflammation 0.30, 0.33, and 0.49; interstitial fibrosis 0.28, 0.32, and 0.67; arterial intimal fibrosis 0.34, 0.42, and 0.59; tubular atrophy 0.35, 0.41, and 0.52; glomeruli thrombi 0.32, 0.53, and 0.85; and global glomerulosclerosis 0.68, 0.70, and 0.77. Pathologists' agreement demonstrated kappas of 0.12 to 0.77. The lower values raise concern about the reliability of using images. Although further research is needed to understand how uploaded images are used clinically, the field may consider higher-quality standards for biopsy photomicrographs.

1580. Characteristics of Early vs. Late Onset Post-transplant Lymphoproliferative Disorder After Liver Transplant:– A Descriptive Study of the United Network of Organ Sharing (UNOS) Database

BackgroundPost-transplant lymphoproliferative disorder (PTLD) is a devastating complication of solid-organ transplant. In liver transplant, studies comparing the risk factors for early vs. late onset PTLD have been limited to single centers. Using a national database, we sought to compare early and late onset PTLD in adult and pediatric liver transplant patients in terms of patient characteristics, immunosuppressive regimens, and mortality.MethodsWe conducted a retrospective analysis of the UNOS database to compare early (<1 year) and late (1+ year) onset PTLD in pediatric (<18) and adult (18+) liver transplant patients. We compared patient demographics, co-morbid conditions, immunosuppressive regimens, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) risk status, reason for transplant, and mortality. We categorized EBV and CMV risk status into high, intermediate, and low based on donor and recipient serostatus. Categorical variables were analyzed using Fisher’s exact test. The Kaplan–Meier method, log-rank test, and multivariable Cox regression were used to examine mortality.ResultsNinety-two pediatric patients and 807 adult patients met study criteria. Overall mortality was 35.87 and 53.78% for pediatric and adult patients, respectively. In adults, unadjusted survival was significantly different for early vs. late onset PTLD (P < 0.001; Figure 1); the latter was associated with a 64.33% decreased mortality risk (95% CI: 51.17–73.95%; P < 0.001). There was no difference in mortality in pediatric patients (P = 0.549). In neither population was EBV risk status associated with early vs. late onset PTLD. In adults, tacrolimus, mycophenolate mofetil (MMF), and steroid maintenance therapy were associated with late onset PTLD (P < 0.001; 0.006; <0.001).Figure 1.ConclusionWe conclude the following: (1) Mortality is greater for early vs. late onset PTLD in adult patients; the converse has been shown previously. (2) Tacrolimus, MMF, and steroids are associated with late onset PTLD in adult patients. (3) EBV risk status did not differ between early and late onset PTLD in both the adult and pediatric populations. This contradicts established reports that EBV negative serostatus of the recipient at the time of transplant is a risk factor for early onset PTLD.Disclosures All authors: No reported disclosures.

Transplantation for the General Surgeon: Care of the Transplant Patient

In this chapter, we review the important clinical aspects of abdominal transplantation relevant to the general surgeon. Whereas only a fraction of readers will go on to specialize in transplantation, most will care for these patients during training. Operative techniques, post-transplantation management, outcomes, and transplantation complications are covered in this chapter. All providers will encounter patients with end-stage organ disease in the course of their careers, and therefore, they must understand the indications for transplantation and considerations for caring for these patients. Likewise, transplant recipients require general surgery procedures, and thus, an appreciation for the unique aspects of caring for this population is essential. This review contains 11 figures, 1 table, and 57 references. Key Words: dialysis, end-organ disease, graft survival, immunosuppression, intestine transplantation, kidney transplantation, liver transplantation, pancreas transplantation, patient survival, United Network of Organ Sharing /Organ Procurement and Transplantation Network

Nonalcoholic Fatty Liver Disease in Children: Beyond Metabolic Syndrome

Nonalcoholic fatty liver disease (NAFLD) has been identified as the number one cause of liver disease in children and adolescents in the United States. This increasing rate of liver disease is directly related to obesity. Often the initial presentation of NAFLD is a child or adolescent with increased risk of cardiovascular and/or metabolic risk factors. According to the United Network of Organ Sharing, NAFLD is rapidly becoming the leading cause of chronic liver disease and liver transplants in older children. It is important for pediatric primary care providers to recognize the risk factors for NAFLD and provide a coordinated, multidisciplinary approach for interventions to prevent and limit liver disease in children and adolescents.

Transplantation crisis at the time of economic recession in Greece

Aim of the study was to assess the effect of economic recession on organ donation and transplantation in Greece. Retrospective data (2002-2016) provided by the Hellenic Transplant Organization (HTO), International Registry in Organ Donation and Transplantation, Eurotransplant, Scandiatransplant, National Health Service Blood and Transplant (NHSBT), and United Network of Organ Sharing (UNOS) databases were analyzed. HTO database was divided into the precrisis (2002-2008) and crisis (2009-2016) era. Donation and transplantation rates between the two periods were compared. Trend estimation analysis was applied on the latter period. Since 2009, organ donation significantly declined without significant change in the reported brain deaths. Overall solid organ transplantations decreased (319.63±70.4 from 460±55.25 transplants/year, P=0.001). Kidney transplantation rates declined (139.38±29.7 from 209.43±20.9 transplants/year, P=0.000), with dramatic reduction in both deceased (99±27.5 from 136.43±131.4 transplants/year, P=0.030) and living donor kidney transplantations (40.38±6.1 from 73±12.5 transplants/year, P=0.000). Liver, heart, and lung transplant rates were not significantly affected; however, they have been low throughout both periods. Convertion to donation has not been affected by the crisis. Time series logistic regression of the crisis period demonstrated declining trends in organ donation, total solid organ transplantation, and deceased donor kidney, liver, and lung transplantation. In 2015, Greek organ donation rates were inferior to Eurotransplant, Scandiatransplant, NHSBT, UNOS, and Italy. There has been a temporal correlation between the economic recession and organ donation and transplantation crisis in Greece. Irrespective of the cause, measures should be taken to reverse this in order to avert the increased morbidity and mortality on the transplant waiting list.

Invited Commentary

Invited Commentary

Contemporary Outcomes of Combined Heart-Liver Transplant in Patients With Congenital Heart Disease

As more patients survive into adulthood with repaired congenital heart disease (CHD), transplant centers now have patients presenting with both end-stage cardiac and hepatic failure. An understanding of the contemporary outcomes with combined heart liver transplantation (CHLT) in patients with CHD is needed. A retrospective review of the outcomes of CHLT in CHD was conducted from October 1, 1987, to June 30, 2015, from the United Network of Organ Sharing (UNOS) database. Propensity score matched cohorts were formed for the assessment of posttransplant outcome: CHLT with CHD, CHLT without CHD, and isolated heart transplant for CHD (HT-CHD). Cohorts were matched based on age, body mass index, inotrope use, and ventilator support at the time of transplant. We assessed 30-day, 1-, 5-, and 10-year posttransplant survivals. There were 61 437 heart transplants during the study period, of which 190 (0.3%) were CHLT. Among CHLT, 41(22%) patients had CHD. In 26 (63%) of these, the indication for CHLT was hepatic congestion/cirrhosis of cardiac origin. In the matched cohorts, the overall survival for CHLT with CHD at 30 days, 1, 5, and 10 years was 95%, 86%, 83%, and 83%, respectively; for CHLT without CHD, it was 100%, 92%, 92%, and 63%, respectively (vs CHLT with CHD: P = 0.49); and for HT-CHD, it was 90%, 84%, 63%, and 39% (vs CHLT with CHD: P = 0.03), respectively. The posttransplant outcome of CHLT, with and without CHD, is comparable. However, there is a trend toward better survival for CHLT for CHD compared with isolated heart transplant for CHD.

Patient and Kidney Allograft Survival in Recipients With End-Stage Renal Disease From Amyloidosis.

Outcomes after kidney transplantation for patients with amyloidosis-associated end-stage renal disease (ESRD) have not been well characterized. We performed a retrospective propensity score matched cohort study with Cox proportional hazards modeling using data from the United Network of Organ Sharing including patients transplanted from 1987 to 2015 (N = 310 629). Amyloidosis patients (N = 576) had higher rates of death (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.28-1.95) and graft loss (HR, 1.49; 95% CI, 1.19-1.87) compared with nonamyloidosis patients. The results were similar when the cohort was restricted to patients transplanted on or after 2001 (HR, 1.72; 95% CI, 1.31-2.26 for death; HR, 1.77; 95% CI, 1.35-2.33 for graft loss). However, there was no significant difference in risk of death or graft loss when amyloidosis patients were compared with those with diabetes-associated ESRD (mortality: HR, 0.99; 95% CI, 0.84-1.17; allograft loss: HR, 1.00; 95% CI, 0.84-1.20), or when compared with elderly patients (age, >65 years at the time of transplant) (mortality: HR, 0.99; 95% CI, 0.81-1.21; graft loss: HR, 1.02; 95% CI, 0.82-1.26). For patients with amyloidosis-associated ESRD deemed suitable for transplantation, patient and graft survivals are diminished compared to kidney transplant recipients overall, but are comparable to other high-risk subgroups.

Proposing a Change in Nevada Revised Statutes Regarding Organ Donation from Non-Death Row Prisoners

According to the United Network of Organ Sharing, every 10 minutes a person is added to the national transplant waiting list. While 22 people waiting for a transplant die each day, 144 people are a...