Post-transplant Graft Failure Research Articles

Highly Sensitized Kidney Transplant Outcomes After the 2014 Kidney Allocation System Change.

Introduction: Kidney Allocation System (KAS) was implemented by United Network for Organ Sharing in 2014 to reduce allocation disparities. Research Questions: Outcomes of highly sensitized patients (calculated panel reactive antibody (cPRA) ≥ 97%) before and after KAS were compared to low-risk recipients (cPRA <10%) in the post-KAS era were examined. The impact on racial disparities was determined. Design: This was a retrospective study of national registry data. Two cohorts of adult candidates waitlisted for deceased donor transplantation during 3-year periods before and after KAS were identified. Results: Highly sensitized patients (N = 1238 and 4687) received a deceased donor kidney transplant between January 1, 2011 and December 31, 2013 and between January 1, 2015 and December, 31, 2017. Racial disparity for highly sensitized patients improved, yet remained significant (P < 0.001), with Black patients comprising 40% and 41% of the highly sensitized candidates and 28% and 34% of the recipients pre- and post-KAS. While posttransplant death-censored graft failure for highly sensitized recipients was similar overall, post-KAS was associated with improved graft survival in the first year after transplant (HR 0.56, 95% CI 0.40-0.78). When compared to contemporaneous lowrisk recipients, both death-censored and all-cause graft failure were similar for highly sensitized recipients and was associated with increased risk for death-censored graft failure beyond the first year (HR 1.39, 95% CI 1.11-1.73). Conclusion: The allocation system led to an increase in transplantation in highly sensitized candidates without compromising outcomes. Although KAS has led to more balanced transplant rates between highly sensitized Black and White patients, racial inequalities persist.

The potential of the ultrasound method in diagnosing pulmonary edema in critically ill patients with liver failure

Background. Pulmonary edema is a common complication in critically ill patients. The liberal tactics of fluid therapy and pathological accumulation of extravascular lung water increase the risks of mortality in Intensive Care Unit patients. Timely and non-invasive diagnosis of pulmonary edema is a primary goal in the intensive care of patients in the Critical Care Unit. We prefer to use lung ultrasound with the registration of B-lines to diagnose lung edema. However, in our country, this method is not validated due to the lack of a sufficient number of clinical studies and necessary regulatory framework.Objective. To assess the potential of diagnostic ultrasonography for pulmonary edema in critically ill patients.Material and methods. A retrospective study was conducted on 27 patients, including 15 males and 12 females aged from 43 to 67 years old (mean age 45.05±17.2 years). All patients were in critical condition due either to acute liver failure, or acute-on-chronic liver failure, or early post-transplant liver graft failure, or posthepatectomy liver failure. Some patients had a systemic inflammatory response syndrome with the development of multiple organ failure and clinical signs of redistribution shock. All patients underwent ultrasound examination of the lungs, and had hemodynamic parameters measured using the transpulmonary thermodilution technique. The data obtained by the two diagnostic modalities were compared.Results. A significant correlation (p&lt;0.05) was found between the extravascular lung water index and the presence of lung edema. We identified a significant correlation (p&lt;0.05) between the number of B-lines and the presence of pulmonary edema. In assessing the relationship between the "B-line" parameter and the "EVLWI" parameter, a strong positive correlation was identified. The area under the ROC curve (AUC) was 0.9±0.06 with a 95% CI [0.77–1.00].Conclusions. Ultrasound data in diagnosing pulmonary edema have a significant correlation with the level of extravascular pulmonary water. Lung ultrasound is an accurate, non-invasive method for assessing extravascular lung water. It can be used for the rapid and accurate diagnosis of pulmonary edema.

Overcoming post-transplant graft failure and adenovirus infection in a patient with FLT3-TKD-mutated mixed-phenotype acute leukemia: A case report.

Mixed-phenotype acute leukemia (MPAL) with FLT3-TKD mutations is a rare and challenging subtype of leukemia. Effective management strategies are crucial for improving patient outcomes. A 31-year-old man with FLT3-TKD-mutated MPAL achieved hematological remission through the JALSG ALL202-O protocol and gilteritinib, followed by cord blood transplantation (CBT). Post-transplant complications included adenovirus-induced hemorrhagic cystitis, managed with bladder irrigation and ribavirin, and engraftment failure, necessitating a second CBT on Day 35. Subsequent adenoviral conjunctivitis resolved with vidarabine. The patient achieved neutrophil engraftment by Day 76 and was discharged on Day 173 without relapse. This case highlights the importance of vigilant supportive care and tailored therapy in managing MPAL with FLT3 mutations, especially in the context of post-transplant complications.

#665 Comparison of outcomes between kidney transplant-naïve and post-transplant graft failure peritoneal dialysis patients

Abstract Background and Aims Despite progress in kidney transplant medicine, there are still patients experiencing graft failure and returning to dialysis therapy. Data regarding the prognosis of these patients remain conflicting. This study was conducted to compare clinical outcomes between transplant-naïve peritoneal dialysis (PD) patients and those returning to PD after a failed allograft. Method In this retrospective cohort study during 2006 and 2016, we included a total of 786 patients on chronic PD. Of them 679 were transplant-naïve, 76 patients underwent a successful transplantation, and 32 patients returned to PD after a failed kidney allograft. Baseline demographics and clinical characteristics were analyzed in relation to the outcomes of all-cause mortality and peritonitis rate. We employed the Kaplan-Meier method and Cox proportional hazards model to evaluate survival, while Poisson regression was utilized to estimate rate ratios for peritonitis. Results During a median follow-up of 6.37 years, 56.68 % death and 146.62 episodes of peritonitis/patient-year were observed. Compared with patients who received a kidney graft, transplant-naïve patients were older, more with diabetes and having higher mortality (58.6 ± 15.8, 40.5% and 57.73%, p &amp;lt; 0.0001). After accounting for age, gender, and comorbidities, the adjusted hazards ratios were 0.26 (95% CI 0.13-0.53) in patients with a functioning graft and 1.12 (95% CI 0.61-2.06) in patients returning to PD after graft failure, compared respectively with concurrent PD patients without kidney transplant. The adjusted relative risk of peritonitis in patients resuming PD after graft failure was comparable to those without kidney transplant (95% CI 0.22-1.14). Conclusion Successful kidney transplant reduced the risk of overall mortality among patients on long-term PD. Patients returning to PD after graft loss showed outcomes similar to transplant-naïve counterparts. These data support reactivation of PD as a viable option for patients with a failed kidney transplant.

The association of socioeconomic status on kidney transplant access and outcomes: a nationwide cohort study in Taiwan.

Conflicting evidence exists regarding the relationship between socioeconomic status and access tooroutcomes after kidney transplantation. This study analyzed the effects of individual and neighborhood socioeconomic status on kidney transplant access and outcomes in Taiwan. We used a retrospective cohort study design and performed comparisons using the Cox proportional hazards model after adjusting for risk factors. Data were collected from the National Health Insurance Bureau of Taiwan data (2003-2012). Patients with high individual and neighborhood socioeconomic status had higher chances of receiving kidney transplants than those with low individual and neighborhood socioeconomic status [adjusted hazard ratio (aHR) = 2.04; 95% CI: (1.81-2.31), p < 0.001]. However, there were no significant differences in post-transplant graft failure or patient mortality in Taiwan between individuals of varying socioeconomic status after five years. When we stratified kidney transplants by domestic and overseas transplantation, there were no significant differences in post-transplant mortality and graft failure, but individualswho received a kidney graft in Taiwanwith high individual and neighborhood socioeconomic status experienced lower risks of graft failure (aHR = 0.55; [95% CI 0.33-0.89], p = 0.017). A relevant disparity exists in accessing kidney transplantation in Taiwan, depending on individual and neighborhood socioeconomic status. However, resultspost transplantation were not different after five years. Improved access to waitlisting, education, and welfare support may reduce disparities.

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.

NephroCAGE-German-Canadian Consortium on AI for Improved Kidney Transplantation Outcome: Protocol for an Algorithm Development and Validation Study.

Recent advances in hardware and software enabled the use of artificial intelligence (AI) algorithms for analysis of complex data in a wide range of daily-life use cases. We aim to explore the benefits of applying AI to a specific use case in transplant nephrology: risk prediction for severe posttransplant events. For the first time, we combine multinational real-world transplant data, which require specific legal and technical protection measures. The German-Canadian NephroCAGE consortium aims to develop and evaluate specific processes, software tools, and methods to (1) combine transplant data of more than 8000 cases over the past decades from leading transplant centers in Germany and Canada, (2) implement specific measures to protect sensitive transplant data, and (3) use multinational data as a foundation for developing high-quality prognostic AI models. To protect sensitive transplant data addressing the first and second objectives, we aim to implement a decentralized NephroCAGE federated learning infrastructure upon a private blockchain. Our NephroCAGE federated learning infrastructure enables a switch of paradigms: instead of pooling sensitive data into a central database for analysis, it enables the transfer of clinical prediction models (CPMs) to clinical sites for local data analyses. Thus, sensitive transplant data reside protected in their original sites while the comparable small algorithms are exchanged instead. For our third objective, we will compare the performance of selected AI algorithms, for example, random forest and extreme gradient boosting, as foundation for CPMs to predict severe short- and long-term posttransplant risks, for example, graft failure or mortality. The CPMs will be trained on donor and recipient data from retrospective cohorts of kidney transplant patients. We have received initial funding for NephroCAGE in February 2021. All clinical partners have applied for and received ethics approval as of 2022. The process of exploration of clinical transplant database for variable extraction has started at all the centers in 2022. In total, 8120 patient records have been retrieved as of August 2023. The development and validation of CPMs is ongoing as of 2023. For the first time, we will (1) combine kidney transplant data from nephrology centers in Germany and Canada, (2) implement federated learning as a foundation to use such real-world transplant data as a basis for the training of CPMs in a privacy-preserving way, and (3) develop a learning software system to investigate population specifics, for example, to understand population heterogeneity, treatment specificities, and individual impact on selected posttransplant outcomes. DERR1-10.2196/48892.

Impact of preexisting coronary artery and peripheral artery disease on outcomes in diabetic patients after kidney transplant.

Atherosclerotic cardiovascular disease is highly prevalent in patients with end-stage kidney disease (ESKD). Kidney transplant (KT) improves patient survival and cardiovascular outcomes. The impact of preexisting coronary artery disease (CAD) and peripheral artery disease (PAD) on posttransplant outcomes remains unclear. This is a retrospective study utilizing the United States Renal Data System. Adult diabetic dialysis patients who underwent first KT between 2006 and 2017 were included. The study population was divided into four cohorts based on presence of CAD/PAD: (1) polyvascular disease (CAD + PAD); (2) CAD without PAD; (3) PAD without CAD; (4) no CAD or PAD (reference cohort). The primary outcome was 3-year all-cause mortality. Secondary outcomes were incidence of posttransplant myocardial infarction (MI), cerebrovascular accidents (CVA), and graft failure. The study population included 19,329 patients with 64.4% men, mean age 55.4 years, and median dialysis duration of 2.8 years. Atherosclerotic cardiovascular disease was present in 28% of patients. The median follow up was 3 years. All-cause mortality and incidence of posttransplant MI were higher with CAD and highest in patients with polyvascular disease. The cohort with polyvascular disease had twofold higher all-cause mortality (16.7%, adjusted hazard ratio (aHR) 1.5, p < 0.0001) and a fourfold higher incidence of MI (12.7%, aHR 3.3, p < 0.0001) compared to the reference cohort (8.0% and 3.1%, respectively). There was a higher incidence of posttransplant CVA in the cohort with PAD (3.4%, aHR 1.5, p = 0.01) compared to the reference cohort (2.0%). The cohorts had no difference in graft failure rates. Preexisting CAD and/or PAD result in worse posttransplant survival and cardiovascular outcomes in patients with diabetes mellitus and ESKD without a reduction in graft survival.

Heart graft preservation technics and limits: an update and perspectives.

Heart transplantation, the gold standard treatment for end-stage heart failure, is limited by heart graft shortage, justifying expansion of the donor pool. Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard practice, but it is usually limited to 240 min. Prolonged cold ischemia and ischemia-reperfusion injury (IRI) have been recognized as major causes of post-transplant graft failure. Continuous ex situ perfusion is a new approach for donor organ management to expand the donor pool and/or increase the utilization rate. Continuous ex situ machine perfusion (MP) can satisfy the metabolic needs of the myocardium, minimizing irreversible ischemic cell damage and cell death. Several hypothermic or normothermic MP methods have been developed and studied, particularly in the preclinical setting, but whether MP is superior to SCS remains controversial. Other approaches seem to be interesting for extending the pool of heart graft donors, such as blocking the paths of apoptosis and necrosis, extracellular vesicle therapy, or donor heart-specific gene therapy. In this systematic review, we summarize the mechanisms involved in IRI during heart transplantation and existing targeting therapies. We also critically evaluate all available data on continuous ex situ perfusion devices for adult donor hearts, highlighting its therapeutic potential and current limitations and shortcomings.

Defining optimal blood pressure control for pre-transplant end-stage renal disease patients: scoping review.

Strict blood pressure control is essential to prevent cardiovascular disease and is associated with decreased mortality. However, in patients with end-stage renal disease awaiting renal transplantation, the level of optimal blood pressure control is not yet defined. Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including 'end-stage renal disease', 'blood pressure', and 'pre-transplant' from their inception to 7 August 2022. Seven observational studies, including one population-based study, were included in the review. Most studies investigated factors associated with post-transplant graft failure or mortality. There was considerable heterogeneity in defining optimal pre-transplant blood pressure measurement frequency among studies (average of three measurements vs. single measurement). One study suggested that low pre-transplant diastolic blood pressure (<50 mmHg) was associated with lower odds of delayed graft failure and mortality. Two studies noted that pre-transplant hypertension, or clinical criteria of hypertension that were present prior to transplant, was associated with post-transplant adverse outcomes. In contrast, one study noted that pre-transplant sustained hypotension with mean blood pressure <80 mmHg, was associated with a higher frequency of delayed graft failure. This systematic review summarizes the current evidence regarding the relationship between pre-transplant blood pressure control and post-transplant outcomes in end-stage renal disease patients. While the results from the included studies are mixed, more stringent blood pressure control than currently practiced may be beneficial to decrease graft failure and mortality in this patient population.

Extracorporeal membrane oxygenation for cardiopulmonary failure in organ donation: Assessing liver transplant outcomes.

Liver transplantation continues to face significant organ shortages and efficient utilization of marginal donors is paramount. This study evaluates the practice patterns and outcomes in liver transplantation when utilizing allografts from marginal donors who required extracorporeal membrane oxygenation (ECMO) support. We performed a retrospective review of the Gift of Life (PA, NJ, DE) organ-procuring organization database for transplants performed using donors supported on ECMO for nondonation purposes. These were cross-referenced to the transplant recipients within the Organ Procurement and Transplantation Network database, and the outcomes of liver transplants using donors on ECMO support were compared with those not requiring ECMO. Organ use and nonuse patterns were then evaluated in ECMO-supported donors, identifying the factors associated with nonuse compared with the factors associated with graft failure. Thirty-nine of the 84 ECMO-supported donors contributing at least one intra-abdominal organ for transplant donated a liver. Graft survival and patient survival up to 5 years were comparable between transplants from ECMO and non-ECMO-supported donors, and no cases of primary nonfunction were seen in the ECMO group. ECMO support was not associated with 1-year graft failure on regression modeling. Additional regression analyses within the ECMO donor population identified bacteremia (HR: 19.81) and elevated total bilirubin at donation (HR: 2.44) as predictive of post-transplant graft failure. Livers from donors supported on ECMO before donation appear safe to use in select transplant settings. Better understanding of the impact of predonation ECMO on liver allograft function will help guide the optimal use of these scarcely used donors.

Inverse association of post-transplant malignancy and graft failure on survival outcome following double lung transplantation.

10629 Background: Graft failure (GF) and post-transplant malignancy (PTM) are common causes of death in lung transplantation. Immunosuppression to prevent graft failure is known to lead to de novo malignancies after solid organ transplantation. Here, we assess the relationship between graft failure and de novo malignancies after double lung transplantation (DLT). Methods: Data extracted from the Organ Procurement Transplantation Network (OPTN) registry were analyzed. DLT cases for non-cancerous diseases were selected. We evaluated the overall survival (OS) of recipients with or without PTM (PTM+ or PTM-), and that of recipients with or without GF (GF+ or GF-) after DLT. The association between GF and PTM was investigated. Results: Among 23,935 DLT recipients, there were 5,629 cases (23.5%) of PTM+ and 18,306 cases (76.5%) of PTM -, and 2,316 cases (9.7%) of GF+ and 21,619 cases (90.3%) of GF- following DLT. Among GF+ cases, the prevalence of acute, hyperacute, and chronic rejection after DLT was 1,962 cases (84.7%). The OS in recipients with GF+ was worse than that in recipients with GF- (p &lt; 0.001). However, inversely, the OS in recipients with PTM+ was better than that of recipients with PTM- (p &lt; 0.001). When patients were categorized into four categories by each factor (GF-, GF+, PTM+, PTM-), the GF rate was lower in recipients with PTM+ than in those with PTM- [GF+/PTM+ (n = 368, 1.5%) versus GF+/PTM- (n = 1,948, 8.1%)] (p &lt; 0.001), and the PTM+ rate was higher in recipients with GF- than in those with GF+ [GF-/PTM+ (n = 5,261, 22.0%) versus GF+/PTM+ (n = 368, 1.5%)] (p &lt; 0.001). And the GF-/PTM+ group showed the best prognosis with 97.3 months of median OS, and the GF+/PTM- group showed the worst prognosis with 36.8 months of median OS (p &lt; 0.001). Conclusions: Recipients who developed PTM following DLT had longer OS compared with those who did not. And the GF rate was significantly lower in recipients with PTM compared to those without PTM. Further research is needed to investigate the underlying mechanism of the inverse association between PTM and GF in DLT recipients.

Factors impacting the medication "Adherence Landscape" for transplant patients.

Medication non-adherence contributes to post-transplant graft rejection and failure; however, limited knowledge about the reasons for non-adherence hinders the development of interventions to improve adherence. We conducted focus groups with solid organ transplant recipients regarding overlooked challenges in the process of transplant medication self-management and examined their adherence strategies and perceptions towards the post-transplant medication regimen. We conducted four focus groups with n=31 total adult transplant recipients. Participants had received kidney, liver, or combined liver/kidney transplant at Johns Hopkins Hospital between 2014 and 2019. Focus groups were audio-recorded and transcribed. Transcripts were analyzed inductively, using the constant comparative method. Responses generally fell into two major categories: (1) barriers to adherence and (2) "adherence landscape". We define the former as factors directly labeled as barriers to adherence by participants and the latter as factors that heavily influence the post-transplant medication self-management process. We propose a shift in the way healthcare providers and researchers, address the question of medication non-adherence. Rather than asking why patients are non-adherent, we suggest that constructing and understanding patients' "adherence landscape" will provide an optimal way to align the goals of patients and providers and boost health outcomes.

OPTN/SRTR 2021 Annual Data Report: COVID-19

This chapter updates the COVID-19 chapter from the 2020 Annual Data Report with trends through February 12, 2022, and introduces trends in COVID-19–specific cause of death on the waiting list and posttransplant. Transplant rates remain at or above prepandemic levels for all organs, indicating a sustained transplantation system recovery following the initial 3-month disruption due to the onset of the pandemic. Posttransplant mortality and graft failure remain a concern in all organs, with rates surging corresponding to waves of the pandemic. Waitlist mortality due to COVID-19 is also a concern, particularly among kidney candidates. While the recovery of the transplantation system has been sustained in the second year of the pandemic, ongoing efforts should focus on reducing posttransplant and waitlist mortality due to COVID-19, and graft failure.

The Impact of Combined Warm and Cold Ischemia Time on Post-transplant Outcomes.

Prolonged warm ischemia time (WIT) and cold ischemia time (CIT) are independently associated with post-transplant graft failure; their combined impact has not been previously studied. We explored the effect of combined WIT/CIT on all-cause graft failure following kidney transplantation. The Scientific Registry of Transplant Recipients was used to identify kidney transplant recipients from January 2000 to March 2015 (after which WIT was no longer separately reported), and patients were followed until September 2017. A combined WIT/CIT variable (excluding extreme values) was separately derived for live and deceased donor recipients using cubic splines; for live donor recipients, the reference group was WIT 10 to <23 minutes and CIT >0 to <0.42 hours, and for deceased donor recipients the WIT was 10 to <25 minutes and CIT 1 to <7.75 hours. The adjusted association between combined WIT/CIT and all-cause graft failure (including death) was analyzed using Cox regression. Secondary outcomes included delayed graft function (DGF). A total of 137 125 recipients were included. For live donor recipients, patients with prolonged WIT/CIT (60 to ≤120 minutes/3.04 to ≤24 hours) had the highest adjusted hazard ratio (HR) for graft failure (HR = 1.61, 95% confidence interval [CI] = 1.14-2.29 relative to the reference group). For deceased donor recipients, a WIT/CIT of 63 to ≤120 minutes/28 to ≤48 hours was associated with an adjusted HR of 1.35 (95% CI = 1.16-1.58). Prolonged WIT/CIT was also associated with DGF for both groups although the impact was more driven by CIT. Combined WIT/CIT is associated with graft loss following transplantation. Acknowledging that these are separate variables with different determinants, we emphasize the importance of capturing WIT and CIT independently. Furthermore, efforts to reduce WIT and CIT should be prioritized.

The Impact of Selection Bias in Transplant Research Intended to Inform Patient Selection: An Example and Potential Solutions.

The Impact of Selection Bias in Transplant Research Intended to Inform Patient Selection: An Example and Potential Solutions.

Outcomes of blood and marrow transplantation in children less than 2-years of age

Allogeneic hematopoietic cell transplantation (Allo-HCT) is a curative option for children with various malignant and non-malignant diseases. Most reports studied all age groups amongst children. Herein we analyzed our data in children transplanted at or less than 2-years of age. We reviewed medical charts of 618 patients who underwent 666 transplantation at our center between 1993 and 2015. There were 340 boys and 278 girls. Median age was 0.7 years (range 0.04-2). Stem cell source was bone marrow (BM) in 492 (73.9%), unrelated umbilical cord blood (UCB) in 161 (24.2%) followed by peripheral blood stem cell (PBSC) in 13 (2%) patients. Matched siblings were the most common donors (n=356, 53.5%), followed by unrelated (n=161, 24.2%) with haploidentical family member donors in 29 (4.4%) transplants. Disease groups were categorized as benign hematology (Thalassemia, Fanconi, Aplastic anemia etc.), benign neoplasm (Langerhans cell histiocytosis, Hemophagocytic Lymphohistiocytosis etc.), non-neoplasms (metabolic disorders, immunodeficiency disorders etc.) and Leukemia/lymphomas (myeloid and lymphoid malignancies etc.). Cumulative incidence of acute GvHD (I-IV) was 31.5% (n=210) and grade III-IV GvHD was 8.7% (n=58). At median follow-up of 115.1 months, the cumulative probability of overall survival (OS) at 5 years was 70.0%±1.9%. Our mortality rate was 31.2% (n=193). The five-year OS was significantly better in patients transplanted for benign hematological disorders (P=.001). Patients transplanted using BM/PBSC as source of stem cells fared significantly better compared to those in which CB was used (P<.001). Post-transplant graft failure remains the leading cause requiring further transplants in this age group. In conclusion, the cumulative probability of OS at 5 years was about 70.0% for all with an OS of 61% in our haploidentical recipients. Analyzing our institutional data over time has enabled us to develop tentative strategies to minimize transplant related toxicities in very young children who are candidates for allo-HCT.

Post-transplant mortality and graft failure after induction immunosuppression among Black heart transplant recipients in the United States

Black heart transplant recipients are more likely to receive induction immunosuppression compared to other races because of higher rates of acute rejection, graft failure, and mortality. However, it is not known whether contemporary induction immunosuppression improves their post-transplant outcomes. To evaluate whether Black patients who were prescribed induction immunosuppression therapy have lower all-cause mortality or graft-failure rates compared to those who were not, we studied Black U.S. adult heart transplant recipients in the Scientific Registry of Transplant Recipients database (2008-2018). We used multivariable Cox proportional hazards regression analysis to compare the hazards of all-cause mortality or graft failure as a composite, for patients who were prescribed induction immunosuppression and those who were not. Among 5160 recipients, 2787 (54.0%) were prescribed induction immunosuppression and 2373 (46.0%) were not. There was no evidence of survival differences according to induction immunosuppression for the composite of all-cause mortality or graft failure (aHR=1.13, 95% CI 0.96-1.32), mortality (aHR=1.14, 95% CI 0.97-1.34), graft failure (aHR=1.05, 95% CI 0.82-1.34) and acute rejection (aHR=1.00, 95% CI 0.89-1.12). Given the side effects of treatment, future guidelines should reconsider the recommendation for induction immunosuppression among Black patients.

342.3: Outcome Analysis of Patients With Genetic Mutations of Complement Regulatory Proteins in Relation to Incidence of Post Renal Transplant Thrombotic Microangiopathy

Introduction: Thrombotic Microangiopathy is an occlusive disorder of microvasculature characterized by thrombocytopenia, systemic or intrarenal platelet aggregation, thrombus formation and hemolytic anemia caused by fragmentation of erythrocytes due to the disturbed microvasculature. TMA developing after renal transplantation can be categorized into either De novo TMA, developing for the first time without any evidence of the disease before the transplant or recurrent TMA where native kidneys have failed due to TMA and recur after kidney transplantation. The contribution of complement regulatory gene (CRG) mutation to post-transplant Thrombotic Microangiopathy (TMA) in Indian kidney transplant recipients (KTR) is unknown. This is a study to determine the association of CRG on post-transplant TMA and graft failure. Methods: A Single Centre, Prospective Observational Cohort Study was undertaken in renal transplant recipients. All live and Deceased donor renal allograft recipients who underwent transplantation from 1st December 2019 onwards till 31st December 2020 were recruited and were followed up for 1 year beyond the last enrolment. Genetic testing was performed with MLPA and Clinical exome sequencing. Results: 78 KTRs with a mean age of 37.09 ± 13.23 years were enrolled. The Native cause of kidney disease in 55 (70.5%) patients was undetermined and 23 (29.5%) had established cause of chronic kidney disease. 58 (74.4%) were males and 20 (25.6%) were females. CRG mutation was seen in 48/78 (61.5%) KTRs. The allele frequency of the CRG mutation was seen in 48/78 (61.53%) of which duplication of CFHR gene was predominantly seen in 40/78 (51.2%) patients. CRG mutation in this cohort was seen more in the younger age group patients. There was no gender predominance for patients with CRG mutation. None of the patients had a mutation for CFH, CFI, CFB, C3, THBD, DGKE genes. One patient had a mutation for the PLG gene. The incidence of post-transplant TMA was seen in 4/78 (5.12%) patients. Mutation related to aHUS was seen in 2 patients. There was no significant difference in serum creatinine levels of patients with or without CRG mutation at the end of 1 year. Conclusion: The prevalence of CRG mutation in our KTR cohort was high and is associated with post-transplant TMA in 50% of patients with de novo TMA. The graft outcome at the end of 1 year was similar in patients with mutation and those without mutation. This study suggests that the presence of CRG mutation should not preclude renal transplantation in patients with ESRD.

Impact of Donor Liver Macrovesicular Steatosis on Deceased Donor Yield and Posttransplant Outcome.

The Scientific Registry of Transplant Recipients (SRTR) had not traditionally considered biopsy results in risk-adjustment models, yet biopsy results may influence outcomes and thus decisions regarding organ acceptance. Using SRTR data, which includes data on all donors, waitlisted candidates, and transplant recipients in the United States, we assessed (1) the impact of macrovesicular steatosis on deceased donor yield (defined as number of livers transplanted per donor) and 1-y posttransplant graft failure and (2) the effect of incorporating this variable into existing SRTR risk-adjustment models. There were 21 559 donors with any recovered organ and 17 801 liver transplant recipients included for analysis. Increasing levels of macrovesicular steatosis on donor liver biopsy predicted lower organ yield: ≥31% macrovesicular steatosis on liver biopsy was associated with 87% to 95% lower odds of utilization, with 55% of these livers being discarded. The hazard ratio for graft failure with these livers was 1.53, compared with those with no pretransplant liver biopsy and 0% to 10% steatosis. There was minimal change on organ procurement organization-specific deceased donor yield or program-specific posttransplant outcome assessments when macrovesicular steatosis was added to the risk-adjustment models. Donor livers with macrovesicular steatosis are disproportionately not transplanted relative to their risk for graft failure. To avoid undue risk aversion, SRTR now accounts for macrovesicular steatosis in the SRTR risk-adjustment models to help facilitate use of these higher-risk organs. Increased recognition of this variable may also encourage further efforts to standardize the reporting of liver biopsy results.