Organ Procurement And Transplantation Network Research Articles

Burden and frequency of viral testing of kidney and non-kidney transplant recipients.

Transplant patients are at risk of infections due to long-term immunosuppression contributing to morbidity and mortality in this population. Post-transplant testing guidelines were established to monitor and guide therapeutic interventions in transplant recipients. We hypothesize that there are gaps in adherence to the recommended frequency of laboratory testing in post-transplant patients. We analyzed national reference laboratory data to compare viral post-transplant infection (PTI) testing frequency with their respective published guidelines to understand patient uptake and compliance. We evaluated the ordering patterns, positivity rates, and frequency of molecular infectious disease tests (MIDTs). We included 345 patients with International Classification of Diseases (ICD)-10 codes for transplant (Z940-Z942, Z944, Z9481, Z9483, Z9484) with at least two tests (within 7 days) in January 2019 and at least one test in December 2020 to find patients in the post-transplant period. We analyzed two cohorts: kidney transplant recipients (KTRs; 40%) and non-KTR (60%) then followed them longitudinally for the study period. In KTR cohort, high-to-low proportion of ordered MIDT was blood BK virus (bBKV) followed by cytomegalovirus (CMV); in non-KTR cohort, CMV was followed by Epstein-Barr virus (EBV). KTR cohort positivity was highest for urine BK virus (uBKV; 58%) followed by EBV (46%), bBKV (40%), and CMV (31%). Non-KTR cohort positivity was highest for uBKV (64%), EBV (51%), CMV (30%), bBKV (8%), and adenovirus (7%). All patients were tested at progressively longer intervals from the date of the first post-transplant ICD-10-coded test. More than 40% of the KTR cohort were tested less frequently for EBV and bBKV, and more than 20% of the non-KTR cohort were tested for EBV less frequently than published guidelines 4 months after transplant. Despite regular testing, the results of MIDT testing for KTR and non-KTR patients in the post-transplant period are not aligned with published guidelines.IMPORTANCEGuidance for post-transplant infectious disease testing is established, however, for certain infections it allows for clinician discretion. This leads to transplant center policies developing their own testing/surveillance strategies based on their specific transplant patient population (kidney, stem cell, etc.). The Organ Procurement and Transplant Network (OPTN) has developed a strategic plan to improve and standardize the transplant process in the US to improve outcomes of living donors and recipients. Publishing national reference lab data on the testing frequency and its alignment with the recommended guidelines for post-transplant infectious diseases can inform patient uptake and compliance for these strategic OPTN efforts.

The impact of the OPTN policy change on patients with a durable left ventricular assist device and chronic kidney disease: Analysis of the UNOS database.

The Organ Procurement and Transplantation Network (OPTN) implemented modifications in 2018 to the adult heart transplant allocation system to better stratify the most medically urgent transplant candidates. We evaluated the impact of these changes on patients supported by a durable left ventricular assist device (LVAD) with chronic kidney disease (CKD). To evaluate the impact of the OPTN policy change on patients supported by durable left ventricular assist devices (LVAD) with chronic kidney disease (CKD). We performed an analysis of patients from the United Network of Organ Sharing Database supported by durable LVAD listed for a heart transplant (HT) between October 17, 2016 and September 30, 2021. Patients were divided into two groups: pre- and postpolicy, depending on whether they were listed on or prior to October 17, 2018. Patients who were on dialysis prior to surgery or discharge were excluded from the analysis. Patients with simultaneous heart and kidney transplants were excluded. Patients who were listed for transplant prepolicy change but transplanted postpolicy change were excluded. This cohort was then subdivided into degrees of CKD based on estimated glomerular filtration rate (eGFR), which resulted in 678 patients (23.7%) in Stage 1 (GFR ≥89.499) (Prepolicy: 345, Postpolicy: 333), 1233 (43.1%) in Stage 2 (89.499 > GFR ≥ 59.499) (Prepolicy: 618, Postpolicy: 615), 613 (21.4%) in Stage 3a (59.499 > GFR ≥ 44.499) (Prepolicy: 291, Postpolicy: 322), 294 (10.3%) in Stage 3b (44.499 > GFR ≥ 29.499) (Prepolicy: 143, Postpolicy: 151), 36 (1.3%) in Stage 4 (29.499 > GFR ≥ 15) (Prepolicy: 21, Postpolicy: 15), and 9 (0.3%) in Stage 5 (15 > GFR) (Prepolicy: 4, Postpolicy: 5). The primary outcome was 1-year and 2-year post-HT survival. There were 2863 patients who met the study criteria (1422 prepolicy, 1441 postpolicy). Overall survival, regardless of CKD stage, was lower following the policy change (p < 0.01). There was a similar risk of primary graft failure (PGF) in the pre- and postpolicy period (1.8% vs. 1.2%, p = 0.26). 1-year overall survival was 93% (91, 94) and 89% (87, 91) in the pre- and postpolicy periods, respectively. 2-year overall survival was 89% (88, 91) and 85% (82, 87) in the pre- and postpolicy periods, respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 1 -year survival was 93% (91, 95), 92% (90,93), 89% (86, 91), 89% (86, 93), 80% (68, 94), and 100% (100, 100), respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 2-year survival was 91% (88, 93), 88% (86, 90), 84% (81, 88), 84% (80, 89), 73% (59, 90), and 100% (100, 100), respectively. Patients with CKD 1 and 2 had better survival compared to those with CKD 3 (p < 0.01) and CKD 4 and 5 (p = 0.03) in the pre- and postpolicy periods. Patients with CKD 3 did not have a survival advantage over those with CKD 4 and 5 (p = 0.25). On cox regression analysis, advancing degrees of CKD were associated with an increased risk of mortality. Patients with LVAD support had decreased overall survival after the OPTN policy change. Patients with more advanced CKD had lower survival than patients without advanced CKD, though they were not impacted by the OPTN policy change.

#2348 Paradoxical association of pre-donation estimated glomerular filtration rate with kidney function decline in living kidney donors

Abstract Background and Aims Living kidney donors (LKD) are at risk for chronic kidney disease (CKD). Whether differences in pre-donation estimated glomerular filtration rates (eGFR) are associated with differences in the rate of post-donation eGFR decline is unclear. We aim to examine the association between pre-donation eGFR and the risk of kidney function decline post-donation. Method A retrospective cohort study using the Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR) database included LKD with pre- and early post-donation eGFR as well as eGFR at 6, 12, and 24 months after donation. The association between the quartile (Q) of pre-donation eGFR and time to ≥35% decline in post-donation eGFR compared to pre-donation eGFR was examined by competing-risks survival regression with death serving as a competing risk variable. Results Of 129,943 LKD ≥18 years old undergoing donation between October 1987 and September 2022, mean ± SD age was 42 ± 12 years and 61% were female. Mean overall pre-donation eGFR was 95.76 ± 29.80 mL/min/1.732 and mean pre-donation eGFR of LKD in Q1, 2, 3, and 4 were 63.50 ± 8.86, 83.05 ± 4.53, 100.30 ± 5.72, and 136.22 ± 23.69 mL/min.1.73 m2, respectively (Ptrend &amp;lt;0.001). Compared to pre-donation eGFR, the mean eGFR at early post-donation was significantly decreased to 53.56 ± 39.81 mL/min.1.73 m2 (mean eGFRpost-pre −43.38 mL/min.1.73 m2; P &amp;lt; 0.001), but mean post-donation eGFR at 6, 12, and 24 months continued trending up to 57.58 ± 45.37, 59.28 ± 43.25, and 61.05 ± 42.51 mL/min.1.73 m2, respectively which were significantly greater than early post-donation eGFR (mean eGFR 6mo-post 4.28, eGFR12mo-post 6.01, and eGFR24mo-post 7.82 mL/min.1.73 m2; P &amp;lt; 0.001; Fig. 1). Median survival for ≥35% decline in post-donation eGFR was 6.43 months (5.50, 11.30) with an incidence rate of 0.08 person-months. Among 75,220 LKD with follow-up data, 58,985 (78%) had the event and 15 (0.02%) died. Compared to LKD with pre-donation eGFR in Q1, LKD in other Q had a significantly higher risk for ≥35% decline in post-donation eGFR with a positively graded association (HR (95% CI)Q2 1.28 (1.23, 1.32); HRQ3 1.41 (1.36, 1.46); and HRQ4 1.60 (1.55, 1.65)). After adjusting for age, gender, race, body mass index, history of hypertension, diabetes, U.S. citizen status, education, and the interaction term between the quartile pre-donation eGFR and race, the magnitude of the association increased but the direction remained (HR (95%C I)Q2 1.41 (1.36, 1.47) HRQ3 1.72 (1.65, 1.79), and HRQ4 2.11 (2.02, 2.20). In addition, race was identified as an effect modifier with an increased risk for ≥35% decline in post-donation eGFR observed in Hispanic/Latino LKD (Pinteraction Q 2, Q3, Q4 0.025, 0.005, and &amp;lt;0.001). Conclusion Higher pre-donation eGFR is associated with a greater risk for post-donation eGFR decline especially among Hispanic/Latino LKD. Candidacy for living kidney donation should not be declined based only on eGFR; while some racial-ethnic minorities may be at greater risk even having higher pre-donation eGFR.

Impact of removing OPTN region from vascularized composite allograft allocation

On 6/18/2020, the Organ Procurement and Transplantation Network (OPTN) implemented new policy replacing OPTN region with a 500 nautical mile (NM) circle around the donor hospital for the purpose of vascularized composite allograft (VCA) allocation. We used OPTN data to assess deceased donor VCA transplants in the 3 years pre- (6/19/2017–6/17/2020) vs. post-implementation (6/18/2020–6/17/2023). A total of 19 deceased donor VCA transplants were performed pre-policy (10 uterus, 3 bilateral upper limb, 1 unilateral upper limb, 3 face, 1 abdominal wall and 1 penis), and 11 post-policy (4 uterus, 1 bilateral upper limb, 2 face, 1 trachea, 2 abdominal wall, and 1 bilateral upper limb and face). Median distance from donor hospital to transplant hospital increased from 70 NM (range: 0–524 NM) pre-policy to 119 NM (range: 0–464 NM) post-policy. The majority of transplants in both policy eras were within 500 NM of the donor hospital [89.5% (N = 17/19) vs. 100% (N = 11/11)] and most remained within the same OPTN region as the donor hospital [68.4% (N = 13/19) vs. 90.9% (N = 10/11)]. Although it is difficult to draw strong conclusions about the policy's impact due to the low transplant volume and timing of implementation relative to the COVID-19 pandemic, data in the 3 years post-implementation suggest that 500 NM circles were a reasonable replacement for OPTN region in VCA allocation. The OPTN will continue to review data to monitor the policy's impact and inform future changes to VCA allocation, such as the transition to continuous distribution, a points-based framework expected to replace the current framework.

Impact of Extracorporeal Membrane Oxygenation Bridging Duration on Lung Transplant Outcomes

BackgroundWe sought to characterize the association between venovenous extracorporeal membrane oxygenation (VV-ECMO) bridging duration and outcomes in patients listed for lung transplantation. MethodsA retrospective observational study was conducted using the Organ Procurement and Transplantation Network (OPTN) database to identify adults (aged ≥18 years) who were listed for lung transplantation between 2016 and 2020 and were bridged with VV-ECMO. Patients were then stratified into groups, determined by risk inflection points, depending on the amount of time spent on pretransplant ECMO: group 1 (≤5 days), group 2 (6-10 days), group 3 (11-20 days), and group 4 (>20 days). Waiting list survival between groups was analyzed using Fine-Gray competing risk models. Posttransplant survival was compared using Cox regression. ResultsOf 566 eligible VV-ECMO bridge-to-lung-transplant patients (median age, 54 years, 49% men), 174 (31%), 124 (22%), 130 (23%), and 138 (24%) were categorized as groups 1, 2, 3, and 4, respectively. Overall, median duration of VV-ECMO was 10 days (interquartile range, 1-211 days), and 178 patients (31%) died on the waiting list. In the Fine-Gray model, compared with group 1, patients bridged with longer ECMO durations in group 2 (subdistribution hazard ratio [SHR], 2.95; 95% CI, 1.63-5.35), group 3 (SHR, 3.96; 95% CI, 2.36-6.63), and group 4 (SHR, 4.33; 95% CI, 2.59-7.22, all P < .001) were more likely to die on the waiting list. Of 388 patients receiving a transplant, pretransplant ECMO duration was not associated with 1-year survival in Cox regression. ConclusionsProlonged duration of ECMO bridging was associated with worse waiting list mortality but did not impact survival after lung transplant. Prioritization of very early transplantation may improve waiting list outcomes in this population.

AI-driven translations for kidney transplant equity in Hispanic populations

Health equity and accessing Spanish kidney transplant information continues being a substantial challenge facing the Hispanic community. This study evaluated ChatGPT’s capabilities in translating 54 English kidney transplant frequently asked questions (FAQs) into Spanish using two versions of the AI model, GPT-3.5 and GPT-4.0. The FAQs included 19 from Organ Procurement and Transplantation Network (OPTN), 15 from National Health Service (NHS), and 20 from National Kidney Foundation (NKF). Two native Spanish-speaking nephrologists, both of whom are of Mexican heritage, scored the translations for linguistic accuracy and cultural sensitivity tailored to Hispanics using a 1–5 rubric. The inter-rater reliability of the evaluators, measured by Cohen’s Kappa, was 0.85. Overall linguistic accuracy was 4.89 ± 0.31 for GPT-3.5 versus 4.94 ± 0.23 for GPT-4.0 (non-significant p = 0.23). Both versions scored 4.96 ± 0.19 in cultural sensitivity (p = 1.00). By source, GPT-3.5 linguistic accuracy was 4.84 ± 0.37 (OPTN), 4.93 ± 0.26 (NHS), 4.90 ± 0.31 (NKF). GPT-4.0 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 4.95 ± 0.22 (NKF). For cultural sensitivity, GPT-3.5 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 5.00 ± 0.00 (NKF), while GPT-4.0 scored 5.00 ± 0.00 (OPTN), 5.00 ± 0.00 (NHS), 4.90 ± 0.31 (NKF). These high linguistic and cultural sensitivity scores demonstrate Chat GPT effectively translated the English FAQs into Spanish across systems. The findings suggest Chat GPT’s potential to promote health equity by improving Spanish access to essential kidney transplant information. Additional research should evaluate its medical translation capabilities across diverse contexts/languages. These English-to-Spanish translations may increase access to vital transplant information for underserved Spanish-speaking Hispanic patients.

Kidney after liver transplantation does not have an increased risk of rejection compared to liver alone.

Simultaneous liver kidney (SLK) transplant protects against acute cellular rejection. In 2017, UNOS implemented a "safety net" policy to allow patients with renal recovery to avoid renal transplantation. Whether kidney after liver transplantation (KALT) increases the risk of rejection is unknown. We performed a retrospective analysis of the Organ Procurement and Transplantation Network (OPTN) database of adult patients who received liver transplant, SLK or KALT between 2010 and 2020. We examined rejection of the liver within 6 months and 1 year of the liver transplant, as well as rejection of the kidney within 6 months and 1 year of receiving the kidney, as well as patient and graft loss. Sixty-six thousand seventy-nine patients were transplanted; 60 168 with liver transplant alone, 5627 with SLK, and 284 with KALT. Acute or chronic liver rejection rates within 6 or 12 months were statistically higher in the KALT group (10.0% and 10.9%) compared to the SLK group (6.1% and 7.5%), but comparable to the LTA group (9.3% and 11.1%). Kidney rejection and graft survival rates were not different. Liver graft survival was worse in KALT than SLK or LTA (Kaplan-Meier estimates.61vs..89 and.90), but these patients were more ill at the time of transplantation. KDPI and LDRI scores were notably lower in the SLK than KALT group. Patient survival was not clinically different between the groups. KALT does not increase the risk of acute or chronic kidney rejection. SLK has a lower risk of early liver rejection, but this effect diminishes by one year to being not clinically different compared to KALT. Given that KALT is immunologically safe, and potentially avoids unnecessary renal graft use, it should be preferred over SLK. Patients undergoing sequential kidney after liver transplant do not have an increased risk of liver or kidney rejection when compared to liver transplant alone or simultaneous liver and kidney transplant.

Impact of removing donation service area and region from pancreas allocation

On March 15, 2021, the Organ Procurement and Transplantation Network (OPTN) replaced donation service area (DSA) and OPTN region as units of pancreas (PA) allocation with a 250 nautical mile (NM) circle with proximity points. We analyzed OPTN data for kidney-pancreas (KP) and PA candidates, transplants, and donors in the 2 years pre-policy (March 16, 2019, to March 14, 2021) and post-policy (March 15, 2021, to March 14, 2023). As expected, more transplants occurred at hospitals outside the recovering organ procurement organization’s DSA post-policy (KP: 32.1% vs 57.3%, P < .001; PA: 61.6% vs 69.3%, P = .09), but the majority stayed within 250 NM (KP: 79.7% vs 85.0%, P < .001; PA: 55.4% vs 61.5%, P = .19). Median preservation time increased from 9.5 to 10.3 hours for KP (P < .001); there was little change for PA (8.5 vs 8.6 hours; P = .99). There were no statistically significant differences in 1-year posttransplant patient mortality or graft failure after implementation for KP (mortality: 3.6% vs 3.2%, P = .60; kidney graft failure: 4.9% vs 5.0%, P = .95; PA graft failure: 9.5% vs 8.9%, P = .65) or PA (mortality: 1.7% vs 2.2%, P = .72; PA graft failure: 12.2% vs 12.6%, P = .88). The removal of DSA and OPTN region from PA allocation has resulted in broader distribution with minimal impact on preservation time or posttransplant outcomes.

Impact of race-neutral eGFR calculations on African American kidney transplant candidate wait time: A single center retrospective analysis.

Race-inclusive estimated glomerular filtration rate (eGFR) could contribute to racial disparity in access to kidney transplantation. The Organ Procurement and Transplantation Network (OPTN) issued a policy allowing waiting time modification for candidates affected by race-inclusive eGFR calculations. Implementation of the new OPTN policy at the kidney transplant program of the Mount Sinai Hospital involved review of 921 African American candidates, of whom 240 (26%) candidates gained a median of 1year and 10months. The duration of time candidates gained varied from a minimum of 5days to a maximum of 12years and 3months; 45.4% gained at least 2years, and 12% gained at least 4years of wait time. Among those who gained wait time, 20 (8.3%) candidates received deceased donor kidney transplants. Candidates who gained wait time had similar sociodemographic characteristics as those who did not, except that the median age for the former was higher by 3years (59 vs. 56). Our early data suggest that the current policy on waiting time modification for candidates affected by race-inclusive estimation of GFR has the potential to improve racial disparity in access to kidney transplantation. However, the generalizability of our findings to other centers requires further study.

Combined Heart Kidney Transplantation Versus Heart Transplant in Patients with Renal Failure: Contemporary Insights and Future Perspectives.

In this review, we aim to outline the criteria regarding the evaluation of patients with chronic renal disease (CKD) awaiting heart transplantation and discuss the outcomes of combined heart/kidney transplantation. Herein, we also review pathophysiology and risk factors that predispose to chronic kidney disease (CKD) and acute kidney injury (AKI) in patients with HF and after OHT. In patients with end-stage systolic heart failure (HF) and an estimated glomerular filtration rate (eGFR) < 30mL/min/1.73 m2, orthotopic heart transplantation (OHT) alone is a relative contraindication, with a consensus that these patients are better served with heart-kidney transplant (HKT). However, there is significant variation between institutions regarding timing and indication for heart/kidney transplantation, with little data available to predict post-transplant outcomes. A Scientific Statement from American Heart Association was published detailing the indications, evaluation, and outcomes for Heart-Kidney Transplantation, and noted a steady rise in the incidence of heart/kidney dual organ transplants. Recently, the Organ Procurement and Transplantation Network (OPTN) Multi-Organ Transplantation Committee implemented a safety net policy for heart transplant recipients who do need meet criteria for simultaneous heart-kidney transplant in 2023 but with a likely need for sequential kidney transplantation. Optimization of organ distribution and patient outcomes after cardiac transplantation requires appropriate recipient selection. This review also outlines the criteria regarding the evaluation of patients with CKD awaiting heart transplantation and outcomes of combined HKT.

Duration of Bridge-to-Transplant Extracorporeal Membrane Oxygenation and Heart Transplant Survival

Background. The 2018 Organ Procurement and Transplantation Network (OPTN) heart allocation policy change prioritizes patients bridged to transplant with mechanical circulatory support (MCS) devices, including extracorporeal membrane oxygenation (ECMO). As a result, the use of ECMO has significantly increased. Methods. We reviewed the OPTN database for adult patients undergoing heart transplant after bridge with ECMO between January 1st 2000 and October 18th 2018. We excluded patients with ≥180 days of ECMO duration, prior transplants, and those using additional MCS devices. Survival and morbidity outcomes of patients with ≥7 days of pre-transplant ECMO were compared to those of patients with &lt;7 days. Results. Of 362 eligible transplant recipients, 163 (45%) utilized &lt;7 days of pre-transplant ECMO and 199 (55%) utilized ≥7 days. Those with ≥7 days were younger (median age: 43 [28–54] vs. 50 [36–57] years, p=0.006) and more likely to have temporary waitlist inactivity (18% vs. 7%, p=0.003) with significantly longer duration of ECMO use (median: 14 [9–24] vs. 4 [2–5] days, p &lt; 0.001). Patients with ≥7 days of ECMO had comparable survival to those with &lt;7 days at one year (81.1% vs. 79.4%, p=0.64) and five years (61.1% vs. 49.3%, p=0.27). After adjustment for clinically relevant variables, duration of ECMO ≥7 days did not increase mortality at five years (HR = 0.90, p=0.59). Conclusions. Longer duration of ECMO (≥7 days vs. &lt;7 days) among patients successfully bridged to transplant is not associated with increased mortality or selected adverse outcome, including graft failure or rejection, at up to five years.

1993. Donor-Derived Transmission of Candida species: 10-year Analysis from the OPTN ad hoc Disease Transmission Advisory Committee (DTAC)

Abstract Background Solid organ transplantation (SOT) is lifesaving, but donor-derived infections can be associated with significant morbidity and mortality. Candida species are common colonizers in deceased donors managed in the intensive care environment, and transmission to the recipient through transplantation is a described phenomenon. We sought to characterize Candida transmission events in the US SOT population. Methods Cases referred to Organ Procurement and Transplantation Network (OPTN) Disease Transmission Advisory Committee (DTAC) between 2012 and 2022 as potential donor disease transmission events (PDDTE) were adjudicated by DTAC based on consensus definitions. We included all recipients from any donor in which ≥1 proven or probable (P/P) or possible transmission of Candida occurred. Results Forty deceased donors were identified (characteristics, Table 1). 124 SOT recipients received organs from these donors including 60 kidney, 27 liver, 15 heart, 14 lung, and 8 multivisceral or other. DTAC adjudications of recipients included 8 proven, 16 probable, 24 possible, 1 unlikely, 51 excluded, and 24 intervention without disease transmission (IWDT). Growth of Candida in culture occurred in 24 of 40 donors and 63 of 124 recipients. Recipients were frequently bacteremic and had Candida growth at site of explanted kidney (Table 2). Mycotic aneurysm, bleed or hematoma occurred in 22 SOT recipients, 10 of which were P/P. Allograft explant was performed in 14 recipients (13 kidney and 1 other), 7 of which were P/P. Within 45 days of PDDTE reports, death occurred in 17 SOT recipients (1 proven, 7 possible, 7 excluded, 1 unlikely, 1 unknown). Only 6 of the 17 recipients who died received antifungal therapy. Seven deaths occurred in the 49 mate recipients of the 24 P/P transmissions, though lack of culture results did not support escalating adjudications beyond possible. Conclusion Donor-derived Candida infections occur with significant associated morbidity, including graft loss, and mortality, especially in kidney recipients. Opportunity exists to further identify risks, improve communication across transplant centers, initiate appropriate antifungal therapy, and improve management of mycotic aneurysm due to candidiasis. Disclosures Jason D. Goldman, MD, MPH, Adaptive Biotechnologies: Collaborative services agreements|Eli Lilly: Advisor/Consultant|Eli Lilly: Grant/Research Support|Eli Lilly: Honoraria|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|GSK: Advisor/Consultant|Karius, Inc.: Advisor/Consultant|Merck: Grant/Research Support|Monogram Biosciences / Labcorp: Collaborative services agreements|Regeneron: Grant/Research Support Anil J. Trindade, MD, CareDx, Inc.: Advisor/Consultant|CareDx, Inc.: Grant/Research Support|Veloxis Pharmaceuticals, Inc.: Grant/Research Support Ricardo M. La Hoz, MD, Takeda: Advisor/Consultant Lara A. Danziger-Isakov, MD, MPH, Aicuris: Contracted Clinical Research|Ansun Biopharma: Contracted Clinical Research|Astellas: Contracted Clinical Research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted Clinical Research|Pfizer: Contracted Clinical Research|Roche Diagnostics: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Contracted Clinical Research

Abstract 13333: Review of Simultaneous Kidney and Heart Transplant After 2018: UNOS Data

Introduction: In October 2018, the Organ Procurement and Transplant Network (OPTN) adopted a 6-tier system for organ allocation where priority was given to critically ill patients, especially those on Extra Corporeal Membrane Oxygenation (ECMO) support. The guideline lacks information about multiorgan transplant due to weak evidence on Simultaneous Kidney and Heart transplant (SKHT) data. Hence with this study, we aim to review outcomes of patients on ECMO at the time of SKHT. Method: This was a retrospective study of adult SKHT recipients between 2018-2022 from the OPTN database. The study excluded individuals who underwent simultaneous multiple organ transplants, isolated heart transplants, as well as those with incomplete outcome information. The cohort was stratified by ECMO need at the time of transplant. Univariate cox regression analysis was performed for predictors of worse outcomes. Patient survival was compared using Kaplan Meier (KM) curve and log rank test. Results: A total of 1383 patients were included in this study, of which 72 (5.2%) were on ECMO bridge. On review of baseline characteristics, patients on ECMO had mean wait time of 65 (± 190) days with higher mortality rate post-transplant and a lower mean survival time as compared to the non-ECMO counterparts (398 (± 404) vs 545 (± 462) days, p= 0.008). On analysis of KM curve, SKHT recipients on ECMO bridge had higher mortality within the first 10 months of transplant and plateaued after that. The only predictors associated with worst outcomes among ECMO recipients were dialysis requirement and development of stroke post-transplant. On the contrary, Left Ventricular assisted device (LVAD) use prior to transplant was associated with 70% reduction in mortality in non-ECMO group (HR: 0.30 (95% CI: 0.11 - 0.83, p=0.02)) in this cohort. Conclusion: Following the change in guidelines, around 5.2% of the total SKHT recipients were on the ECMO bridge. Dialysis requirement and development of stroke post-transplant was independently associated with higher mortality compared to non ECMO group. On the contrary, patients on LVAD support at the time of transplant have had better outcomes.Figure 1:

Outcome of Organ Procurement and Transplantation Network (OPTN) Policy Allowing for Waiting Time Modification for Candidates Affected by Race-Inclusive eGFR Calculations: Early Impact from a Single Center

Outcome of Organ Procurement and Transplantation Network (OPTN) Policy Allowing for Waiting Time Modification for Candidates Affected by Race-Inclusive eGFR Calculations: Early Impact from a Single Center

Applying propensity methods to the United States transplant registry for external real-world evidence control arms for 5-year survival in the BENEFIT study

To address the challenges of assessing the impact of a reasonably likely surrogate endpoint on long-term graft survival in prospective kidney transplant clinical trials, the Transplant Therapeutics Consortium established a real-world evidence workgroup evaluating the scientific value of using transplant registry data as an external control to supplement the internal control group. The United Network for Organ Sharing retrospectively simulated the use of several distinct contemporaneous external control groups, applied multiple cause inference methods, and compared treatment effects to those observed in the BENEFIT study. Applying BENEFIT study enrollment criteria produced a smaller historical cyclosporine control arm (n = 153) and a larger, alternative (tacrolimus) historical control arm (n = 1069). Following covariate-balanced propensity scoring, Kaplan-Meier 5-year all-cause graft survivals were 81.3% and 81.7% in the Organ Procurement and Transplantation Network (OPTN) tacrolimus and cyclosporine external control arms, similar to 80.3% observed in the BENEFIT cyclosporine treatment arm. Five-year graft survival in the belatacept-less intensive arm was significantly higher than the OPTN controls using propensity scoring for comparing cyclosporine and tacrolimus. Propensity weighting using OPTN controls closely mirrored the BENEFIT study’s long-term control (cyclosporine) arm’s survival rate and the less intensive arm’s treatment effect (significantly higher survival vs control). This study supports the feasibility and validity of using supplemental external registry controls for long-term survival in kidney transplant clinical trials.

The history of ethical principles in liver transplant organ allocation in the united states: how historical and proposed allocations system fare in balancing utility vs. urgency and justice vs. pragmatism.

The United States (US) liver transplant community is processing changes to the allocation system and developing a new proposal that will result in even greater change. This review evaluates the ethical implications of these decisions, focusing on two sets of competing ethical principles (Urgency vs. Utility and Justice vs. Pragmatism). About four years ago, the Organ Procurement and Transplantation Network (OPTN) implemented the Acuity Circle Model to replace the geographic boundaries of organ procurement organizations (OPOs). Here, we review how effectively this model reduced regional variation in access and improved waitlist survival. Likewise, the OPTN is planning to transition to a continuous distribution model which will redefine the scoring systems for allocation. We will discuss how the ethical priorities discussed above should be considered while developing the new system. Every change in organ allocation policy must balance competing ethical imperatives. Although our community's emphasis on urgency over utility is appropriate, we should study the potential benefits of considering utility in the system. Meanwhile, our push for more Justice in the system should remain our imperative and Pragmatism should only be considered to minimize the costs of these changes.

Building analytical models for predicting de novo malignancy in pancreas transplant patients: A machine learning approach

This research aimed to predict de novo malignancy in patients who underwent pancreas transplants using a machine learning approach. We constructed various predictive models based on data from the Organ Procurement and Transplantation Network (OPTN) to classify malignant patterns in transplant patients. The models were trained using medical records spanning from 1987 to 2020 to identify essential prognostic components associated with malignancy development. Various datasets from the United Network for Organ Sharing Standard Transplant Analysis and Research (UNOS-STAR) database were used to evaluate each model's performance using the areas under the receiver operating characteristic (ROC) and precision-recall (PR) curves. Our findings demonstrated the effectiveness of machine learning in predicting de novo malignancy in pancreas transplant patients. Specifically, we identified the recipient’s B2 and DR1 antigens and the donor’s DDAVP hormone as significant factors associated with malignancy. Our study highlights the importance of integrating medical records from various sources to enhance the accuracy of predictive models for organ transplantation.

Continuous allocation: The problem with EPTS and pediatric kidney candidates.

The 2014 Kidney Allocation System (KAS) introduced longevity matching for adult candidates using the Estimated Post-Transplant Survival (EPTS) score, which includes candidate age, time on dialysis, diabetes status, and number of previous solid organ transplants. The proposed continuous distribution framework may expand the use of this attribute to pediatric candidates, but there is no data on its performance among pediatric kidney transplant recipients. We performed a retrospective cohort study of 6800 pediatric kidney transplant recipients from 2001 to 2011 using Organ Procurement and Transplantation Network (OPTN) data. EPTS score was calculated for each patient and compared to reported patient survival to estimate the validity of the score in children. The median age of patients was 14.01 years (IQR 9.29-16.37 years), and dialysis vintage was 0.67 years (IQR 0-1.82 years). 18.2% of the cohort had a prior transplant and 1% had diabetes. Median EPTS score was 2 (IQR 1-2). Seven percent of patients died during the study period and 54.7% of the cohort was censored prior to 10 years. The c-statistic was 0.505 (95% CI: 0.49-0.53). Overall, EPTS is not a valid predictor of patient survival among pediatric kidney transplant recipients.

Applying Analytics to Design Lung Transplant Allocation Policy

In 2019, the United Network for Sharing (UNOS), which has been operating the Organ Procurement and Transplantation Network (OPTN) in the United States since 1984, was seeking to design a new national lung transplant allocation policy. The goal was to develop a point system that would prioritize candidates on the waiting list in a way that would yield more efficient and equitable outcomes. Our joint Massachusetts Institute of Technology (MIT)/UNOS team joined forces with the OPTN Lung Transplantation Committee in these policy design efforts. We discuss how our team applied a novel analytical framework, which was developed at MIT and utilizes optimization, regression, and simulation techniques, to illuminate salient trade-offs among outcomes and guide the choice of how to weigh different point attributes in the allocation formula. The committee selected for the allocation formula weights that were highlighted in the team’s analysis. The team’s proposal was implemented as the national lung allocation policy on March 9, 2023 across the United States. History: This paper has been accepted for the INFORMS Journal on Applied Analytics Special Issue—2022 Daniel H. Wagner Prize for Excellence in the Practice of Advanced Analytics and Operations Research.

Association of postoperative length of stay with outcomes following orthotopic heart transplantation-A national analysis.

In the absence of standardized recovery protocols, there is little evidence to guide postoperative care to ensure optimal in-hospital and long-term outcomes following heart transplantation (HT). Using two national databases, we examined the association between postoperative length of stay (LOS) with patient/graft survival, index hospitalization costs, and non-elective readmissions. Adult HT recipients from 2010 to 2019 were identified and analyzed within the Organ Procurement and Transplantation Network (OPTN) Database and Nationwide Readmissions Database (NRD). The risk-adjusted relationship between 1-year mortality and LOS was assessed with restricted cubic splines and subsequently used to stratify patients into Expedited (7-11 days), Routine (12-16 days), and Delayed (>16) discharge groups. Survival outcomes were analyzed using Restricted Means Survival Time analysis (RMST) and multivariable Cox models. Of 9995 HT recipients within the OPTN, 3777 (38%) were categorized as Expedited, and 3040 (30%) as Routine. After adjustment, expedited discharge was not associated with inferior 90-day (ΔRMST -.01, p=.91) and 1-year patient survival (ΔRMST -.02, p=.53). Additionally, expedited was not associated with increased odds of non-elective readmission at 90-days (HR 1.04, CI .77-1.43) relative to Routine discharge. Counterfactual analysis revealed an estimated cost saving of $50 million if all Routine patients received an expedited discharge. Expedited discharge after HT seems to be cost-effective and is not associated with inferior outcomes. Institutional-level outcome analyses should be performed to identify patients that would benefit from expedited discharge, and future studies should analyze the feasibility of implementing standardized discharge protocols following HT.