Graft Failure Research Articles

Evaluating the safety of immune checkpoint inhibitors prior to liver transplant.

614 Background: Liver transplantation (LT) offers a 5-year survival exceeding 70% for selected patients with hepatocellular carcinoma (HCC). Immune checkpoint inhibitors (ICIs) may be used to downstage or bridge to transplantation. This study aims to evaluate the safety of ICIs prior to LT. Methods: Multicenter retrospective study, involving 9 centers, included adults who received ICIs and, subsequent LT, between 2019 and 2023. The ICI cohort was matched by age, sex, liver diseases and transplant date (1:3) with a similar cohort of HCC transplanted patients that did not receive ICIs. Results: The ICI cohort included 45 patients (Table part 1). The most common underlying liver diseases were viral. 15.5% of patients had macrovascular invasion and, 62.2% multifocal disease. The most commonly used ICI was nivolumab (75.6%), followed by atezolizumab-bevacizumab (17.8%). The median follow up was 32.5 months (17.4 - 47.6). The median ICI duration was 147 days (129.5-276.5), with a median interval of 58 days (22–193) between the last ICI dose and LT. There were 8 (17.8%) cases of graft rejection, 2 steroid-resistant leading to 1 graft failure. There were 4 (8%) HCC recurrences. During follow-up there were 6 deaths, 2 related to HCC recurrence and 4 non liver related. When compared with 135 non-ICI cohort patients, there were no differences within the groups (Table part 2). Importantly, we found no significant differences in crude rejection rates (p=0.5). Conclusions: Our study suggest that ICI treatment prior to LT is safe. ICI rejection primarily occurs in the acute post-transplant period (within 3 months), with a low risk of death due to graft failure. Further clinical trials are needed. Part 1: ICI cohort descriptive analysis. N (%); Median (IQR); Part 2: Comparison between cohorts. N (%); Mean (SD). (part 1) ICI-cohort n=45 General data Male 38 (84.4) Age 61.2 (7.6) Etiology of liver diseases Hepatitis C 17 (37.8)Hepatitis B 6 (13.3)MASLD 6 (13.3)Viral +Alcohol 5 (11.1)Alcohol 3 (6.7)Autoimmune 3 (6.7)Other 3 (6.7)Combined viral 2 (4.4) Largest tumor (mm) 39 (22) Macrovascular invasion 7 (15.5) Multifocal 28 (62.2) Locoregional therapy 36 (80.0) Number of locoregional therapies 2 (2) Immunotherapy Nivolumab 34 (75.6) Atezolizumab/bevacizumab 8 (17.8) Pembrolizumab 1 (2.2) Nivolumab+pembrolizumab 1 (2.2) PD1 inhibitor clinical trial 1 (2.2) Days of ICI treatment 147 (203) Radiological tumor response ICI No 17 (37.8) Transplant Deceased donor 43 (95.6) Washout period (days) 58 (171) Induction therapy (anti-thymoglobulin) 8 (17.8) Outcomes Rejection Biopsy proven 8 (17.8) 8 (100) Time to rejection (days) 43 (102) Graft failure Rejection 2 (4.4)1 (2.2) HCC recurrence 4 (8) Deaths 6 (13.3) Follow up Since transplant (months) 32.5 (30.2) (part 2) ICI-cohort (n=45) Non-ICI cohort (n= 135) P Post transplant rejection rate 8 (17.8) 32 (23.7) 0.53 Time to rejection (days) 180.1 (SD 218) 62.2 (SD 62.8) 0.25 Overall deaths 6 (13.3) 10 (7.4) 0.36

Role of vesicoureteral reflux on pediatric kidney allograft function.

Vesicoureteral reflux (VUR) is a common urologic complication of pediatric kidney transplant, though there is little data on the effect of VUR on histologic graft changes or graft survival. All pediatric patients who received a kidney transplant from 2007 to 2020 were selected for retrospective chart review. All participants underwent a voiding cystourethrogram (VCUG) at a 6-month post-transplant. Patients were then categorized into two groups based on vesicoureteral reflux grade: no/low-grade VUR (grades 0-2) and high-grade VUR (grades 3-5). Outcomes collected included graft failure rates, graft function, urinary tract infections(UTIs), proteinuria, and Banff scores at 3- and 12-month post-transplant surveillance kidney biopsies. There were 74 pediatric patients who received a kidney transplant in the designated time-period, and of those 39 had no/low-grade VUR and 35 had high-grade VUR. There was no difference in graft failure among the two groups over time when stratified for age (p = 0.389, CI 0.53-5.08). Patients with high grade VUR had a higher risk of UTI development overall (RR 1.89, 95%CI 1-3.6, p = 0.041), mostly accounted for from increased development of febrile UTI (RR 1.66, 95%CI 1.1-2.6, p = 0.038). Unselected pediatric kidney transplant recipients with high-grade vesicoureteral reflux on VCUG at a 6-month post-kidney transplant are more likely to have febrile UTI compared to those in the low-grade VUR group. There is no difference in graft survival among the two groups.

Access to Kidney Transplantation for Minority Children With End-Stage Renal Disease and Predictors of Post-Transplant Outcome: Impact of Race and Ethnicity.

Racial disparities in access to kidney transplantation (KT) have been described among children with end-stage renal disease in the United States. It has been suggested that these disparities stem from a combination of clinical and socioeconomic factors. We evaluated data from the US Scientific Registry of Transplant Recipients (SRTR) of all pediatric (< 18 years old) KT recipients from 1999 to 2014 and compared outcomes by race or ethnicity: Hispanic, non-Hispanic Whites (NHW), and non-Hispanic Blacks (NHB). We assessed 1- and 5-year patient survival (PS) and death-censored graft survival (DCGS) using Kaplan-Meier survival cures. Multivariate logistic regressions of graft failure by 1 and 5 years examined effects of race/ethnicity by controlling for donor and recipient characteristics including living or deceased donor, recipient age, BMI, re-transplant status, cPRA, HLA mismatch, graft rejection, cold ischemia time (CIT), and type of insurance. During the 15-year period, 11 740 (6596 NHW, 2306 NHB, and 2838 Hispanic) pediatric KT recipients were performed in the United States. Compared to NHW (250 ± 335 days), NHB (293 ± 348; p < 0.001) and Hispanics (322 ± 353; p < 0.001) spent more time on the waitlist. One-year PS for NHW, NHB, and Hispanics was 98.6%, 98.6%, and 99.0%, respectively; one-year DCGS was 95.5%, 93.7%, and 96.0%, respectively. Five-year PS for NHW, NHB, and Hispanics was 95.5%, 93.1%, and 95.5%, respectively; five-year DCGS was 80.7%, 60.3%, and 76.3%, respectively. Multivariate analysis showed that higher recipient cPRA (OR 1.0, 95% CI 1.0-1.0; p = 0.005), greater HLA mismatch (OR 1.1, 95% 1.0-1.3; p = 0.008), rejection (OR 3.9, 95% CI 2.1-7.0; p < 0.001), and secondary kidney transplantation (OR 15.0, 95% CI 11.5-19.4; p < 0.001) were associated with 1-year graft loss; older recipient age (OR 1.1, 95% CI 1.1-1.1; p < 0.001), higher recipient cPRA (OR 1.0, 95% CI 1.0-1.0; p < 0.001), greater HLA mismatch (OR 1.1, 95% CI 1.0-1.1; p = 0.002), rejection (OR 2.0; 95% CI 1.3-3.0; p = 0.001), and secondary kidney transplantation (OR 11.2, 95% CI 9.6-13.0; p < 0.001) were predictive of 5-year graft loss. Patients with public insurance have higher risks of 1-year and 5-year graft loss (p < 0.001) than those with private insurance payers. Racial and ethnic minority children in the United States have lower access to KT with clinical outcomes suggesting a disparate trajectory. NHB demonstrate unfavorable DCGS while Hispanic children have comparable or better DCGS and PS outcomes compared to NHW. Elucidating the clinical or socioeconomic roots of these differences may identify mitigating measures that can improve KT outcomes for these minoritized populations.

Clinical Outcomes and Donor-specific Antibody Rebound 5 y After Kidney Transplant Enabled by Imlifidase Desensitization.

Imlifidase is an IgG-cleaving endopeptidase conditionally approved in Europe for desensitization of highly sensitized patients before kidney transplantation. We present 5-y outcomes and donor-specific antibody (DSA) levels for clinical trial participants from a single site who received imlifidase for desensitization before incompatible transplantation (NCT02790437). Imlifidase was administered up to 24 h before living or deceased donor kidney transplantation. DSAs were monitored before transplantation, at days 7 and 28, and at 5 y posttransplant. At 5 y, 7 of 8 participants were alive. One of these 7 had suboptimal graft function secondary to donor-derived disease but remained dialysis independent. Three participants had antibody-mediated rejection (AMR), which occurred in the first 30 d in all cases and was successfully treated. No new episodes of suspected or biopsy-proven AMR occurred after 30 d posttransplant. Seven participants had DSA rebound. DSAs commonly persisted 5 y posttransplant, although they were generally lower strength compared with pre-imlifidase. Dilution studies of sensitized serum enabled the identification of lower AMR risk phenotypes for persisting DSAs. Severe and/or opportunistic infections were not observed at greater than expected frequency. Five-year outcomes of imlifidase-enabled incompatible transplants are overall favorable. DSA rebound is common, but antibody strength lessens in the long term, and longitudinally persisting DSAs did not lead to premature graft failure.

Newborn Screening for Hurler Syndrome Facilitates Early Transplant and Good Outcomes

Hematopoietic cell transplantation (HCT) is the standard of care treatment for children with Hurler syndrome (HS). This study describes the impact of newborn screening (NBS) on HCT outcomes for these patients. Retrospective study of HS patients diagnosed through NBS and referred to Duke from 2017 to 2023. Patients received a myeloablative busulfan-based regimen and unrelated umbilical cord blood HCT, with cyclosporine and mycophenolate for graft-versus-host-disease prophylaxis. Patients (N=9) were transplanted at a median age of 5.2 months and median weight of 7.8 kg. Median reinfused total nucleated cell was 14.8× 107/kg. The median times to neutrophil and platelet engraftment were 17 and 48 days, respectively. No primary graft failures or rejections were observed. Post-HCT complications included sinusoidal obstructive syndrome, microangiopathy and autoimmune hemolytic anemia. At median follow-up of 29.1 months (range 4.1-72.2), 8 of 9 patients were alive with normal alpha-L-iduronidase (IDUA) levels, Lansky scores of 90-100%, and developing milestones. One patient died due to autoimmune hemolytic anemia on day+139 (with normal IDUA level and >98% donor chimerism at day+100). Early umbilical cord blood transplant during infancy of HS patients diagnosed through NBS is safe, feasible, and corrects IDUA enzyme deficiency. Follow-up studies will ascertain the long-term benefits of this approach.

Computational fluid dynamics to simulate stenotic lesions in coronary end-to-side anastomosis.

End-to-side anastomosis is common in coronary artery bypass grafting, although restrictive suturing can narrow the anastomosis. We evaluated ex vivo end-to-side models by numerically simulating fluid dynamics to compare various degrees of stenotic anastomoses to predict haemodynamic effects. A carotid artery was grafted via an end-to-side anastomosis onto the left anterior descending artery of a porcine heart, with liquid silicone injected into the vessels. The end-to-side image was acquired via multidetector computed tomography for reference, and models of longitudinal shortening and bilateral narrowing were created with 25%, 50%, 75%, along with 90%, and 100% stenosis in the native coronary artery. Haemodynamics were analyzed using computational fluid dynamics simulations to calculate streamlines, wall shear stress, and oscillatory shear index. In the reference model, the graft inflow impinged on the floor of the native artery, creating a recirculating vortex and a high oscillatory shear index region near the heel. As the graft flow angle increased with longitudinal stenosis, bilateral stenosis generated helical flow near the lateral wall of the native artery, worsening with increased stenosis. At 75% stenosis, both longitudinal shortening and bilateral narrowing caused abnormal flow separation, with low wall shear stress and high oscillatory regions forming distal to the toe of the anastomosis. Computational fluid dynamics modelling predicts that end-to-side anastomoses with 75% longitudinal or bilateral stenosis are at a risk of intimal hyperplasia causing graft failure, while anastomotic stenosis <50% indicates acceptable haemodynamics. Future studies should explore long-term clinical outcomes with suboptimal surgical anastomotic construction.

Factors Associated With Long-term Kidney Allograft Survival: A Contemporary Analysis of the UNOS Database.

Various clinicopathologic markers, such as 1-year serum creatinine (Cr), have been used to prognosticate kidney allografts after transplantation. However, a contemporary analysis of their relationship with long-term graft survival is lacking. This study aimed to analyze recent data on the association of prognostic factors with kidney allograft survival in patients who underwent transplantation in the modern era. Adult kidney-transplant recipients in the UNOS database (2008-2020) were identified. Living and deceased donor allografts were analyzed separately and stratified by 1-year serum Cr level: ≤1.0, 1.0 to 1.5, 1.5 to 2.0, and >2.0 mg/dL. Time-to-event analysis was performed with long-term death-censored graft survival as the primary outcome. In addition, factors associated with raised 1-year serum Cr and with long-term allograft failure were identified. 174,547 patients were included. Ten-year survival decreased with increasing 1-year creatinine, and these trends persisted on adjusted analysis for both living donor (Cr ≤ 1.0 mg/dL: reference; Cr 1.0-1.5 mg/dL aHR = 1.77 [1.59-1.96]; Cr 1.5-2.0 mg/dL aHR = 3.24 [2.89-3.64] and; Cr > 2.0 mg/dL aHR = 9.78, [8.64-11.07], P < .01) as well as deceased donor allografts (Cr ≤ 1.0 mg/dL: reference; Cr 1.0-1.5 mg/dL aHR = 1.74 [1.63-1.86]; Cr 1.5-2.0 mg/dL aHR = 3.06 [2.84-3.30] and; Cr > 2.0 mg/dL aHR = 8.51, [7.89-9.18], P < .01). These results characterize the association between 1-year serum creatinine levels and other clinicopathologic factors with long-term kidney allograft survival. We demonstrate the ability of prognostic factors to stratify patients by risk of graft failure in a contemporary patient cohort that is representative of current practice and outcomes.

Post-transplant Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) is a challenging and serious complication of kidney transplantation that significantly impacts graft and patient survival, occurring in 0.8-15% of transplant recipients. TMA is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury due to endothelial damage and microthrombi formation in small vessels. However, clinical features can range from a renal-limited form, diagnosed only on a kidney biopsy, to full-blown systemic manifestations, which include neurological, gastrointestinal, and cardiovascular injury. TMA can arise due to genetic or acquired defects such as in complement-mediated TMA or can occur in the context of other conditions like infections, autoimmune diseases or immunosuppressive drugs, where complement activation may also play a role. Recurrent TMA after kidney transplant is almost always complement-mediated, although complement overactivation may also play a role in de novo post-transplant TMAs associated with ischemia-reperfusion injury, immunosuppressive drugs, antibody-mediated rejection, viral infections, and relapse of autoimmune diseases such as, antiphospholipid antibody syndrome. Differentiating between a complement-mediated process and one triggered by other factors is often challenging but critical to minimize allograft damage since the former is non-responsive to supportive therapy, needs long-term anti-complement therapy and has a high risk of recurrence. Given the central role of complement and impact of genetic defects on the risk of recurrence in many forms of post-transplant TMA, genetic testing for complement disorders is key for proper diagnosis and management. Given that complement activation may also play a role in a subset of TMAs associated with other conditions, prompt recognition and timely initiation of anti-complement therapy is equally important. Additionally, TMA associated with non-complement genes, often part of a broader syndromic process with distinct clinical features, has also been described. Early identification and treatment are essential to prevent graft failure and other severe complications. This review explores the pathophysiological mechanisms underlying various post-transplant TMAs.

Selection of intraoperative fluid for kidney transplantation

The kidney, the most frequently transplanted organ, represents the optimal treatment for end-stage renal disease. Transplanted kidneys are highly vulnerable to perioperative injuries such as hypotension and hypovolemia, which can be influenced by perioperative fluid management. Postoperatively, delayed graft function increases the risk of graft failure. Although adequate volume administration can reduce delayed graft function, the type of intraoperative fluid most likely to benefit and support graft function remains unclear. Traditionally, crystalloids have been the primary choice for fluid management during kidney transplantation. Among these, 0.9% sodium chloride is the most commonly used, as its potassium-free composition minimizes the risk of hyperkalemia in patients with end-stage renal disease. Albumin is not routinely used, whereas synthetic colloids are discouraged owing to their nephrotoxicity. To date, 0.9% sodium chloride has demonstrated fewer advantages compared with balanced crystalloids, particularly regarding acid-base homeostasis, electrolyte balance, and delayed graft function. This review aims to examine the existing evidence on the effect of crystalloids and colloids on postoperative graft function and to recommend an appropriate fluid regimen, including balanced crystalloids, for kidney transplantation.

Fewer medullary pyramids in the living kidney donor associate with graft failure in the recipient.

This study aimed to identify the parenchymal structural features by both CT and histology that associate with death-censored graft failure in recipients of living donor kidneys. We analyzed kidney recipients of ABO-compatible living donor kidneys from 2000-2020 with follow-up through 2023. Cortical volume and thickness, individual medullary pyramid volume and count, glomerular volume, nephrosclerosis, and nephron number were assessed by deep learning models applied to the predonation CT and by morphometric histology analysis from the biopsy at the time of transplantation. There were 3098 recipients followed a median 5 years with 346 graft failure events. In adjusted analyses, the only structural measures associated with graft failure were fewer medullary pyramids on CT and a higher fraction of interstitial fibrosis and tubular atrophy (IFTA) on histology. Having ≤15 pyramids donated occurred in 9% and was associated with a graft failure incidence of 2.5 per 100 person-years compared to 1.6 per 100 person-years in the 17% with ≥26 pyramids donated. Fewer medullary pyramids were associated with a lower 1-year eGFR, which mediated the subsequent risk of graft failure. IFTA >1% is also associated with graft failure. Medullary pyramid count is a potentially useful predonation prognostic biomarker for graft failure in transplant recipients.

Graft-repositioning technique using infusion and small bubbles during Descemet’s membrane endothelial keratoplasty

BackgroundDescemet’s membrane endothelial keratoplasty (DMEK) is a highly effective procedure for corneal endothelial dysfunction; however, once a DMEK graft is deployed, repositioning can be challenging. Therefore, this study aimed to evaluate the efficacy of a technique that utilizes infusion and small air bubbles to reposition a misaligned deployed graft.MethodsThis retrospective interventional case series enrolled patients who underwent DMEK between January 2022 and July 2023, including cases where the DMEK graft was attached and unfolded in off-center positions”. Experienced surgeons performed DMEK by inserting an infusion cannula and positioning a small bubble in the anterior chamber after the graft unfolded off-center. The eye was tilted in a deviated direction, and the cornea was massaged from the corneal limbus to the center using a 27-gauge blunt needle. Before and after DMEK, we measured the best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), and endothelial cell density (ECD). Additionally, we monitored the incidence of postoperative complications.ResultsSix eyes of six patients were included in this study. Postoperatively, the overall BSCVA and CCT of the eyes improved (P < 0.001). However, one eye developed recurrent uveitis and required a sub-Tenon’s capsule triamcinolone acetonide injection. No eyes required re-bubbling, and no instances of primary graft failure were observed.ConclusionThe described technique enables the safe and feasible repositioning and unfolding of the DMEK graft.

P-2275. Impact of Epstein-Barr Virus (EBV) Donor Serostatus on Post-transplant Mortality and Post-Transplant Lymphoproliferative Disorder in Thoracic Organ Transplant EBV-Seropositive Recipients: Data from the Organ Procurement and Transplantation Network

Abstract Background Epstein Barr Virus (EBV) donor positive (D+) serostatus is a risk factor for Post-Transplant Lymphoproliferative Disorder (PTLD) in EBV-seronegative recipients. The impact of donor EBV serostatus on mortality and PTLD in EBV-seropositive recipients (R+) in thoracic organ transplant (TOT) is unknown.Table 1.Baseline demographic and clinical characteristics of EBV D-/R+ and EBV D+/R+ TOT recipients Methods Using the Organ Procurement and Transplantation Network database, we identified 47,201 EBV R+ TOT recipients between 01/2004 – 12/2021. The primary exposure was EBV D+ and the primary outcomes were death and PTLD. Multivariable Cox regression models were used to assess the relationship between donor EBV serostatus and the outcome of death and PTLD.Figure 1.Kaplan-Meier survival plots for EBV D-/R+ (solid line) versus EBV D+/R+ (dashed line) post heart (red line) and lung (blue line) transplantation Results Of 47,201 EBV R+ TOT recipients, 48.5% were lung and 51% were heart transplant recipients. The majority (93.4%) were EBV D+/R+, with median age of 59 years and 66.8% males. EBV D-/R+ and D+/R+ TOT recipients differed in CMV donor and recipient status, donor median age, sex, and graft failure (Table 1). The incidence rate of death was 7.2 per 100 person-years in EBV D+/R+ compared to 6.9 per 100 person-years in EBV D-/R+, p=0.156. Survival did not differ by EBV donor status, but it was lower in lung transplant (Figure 1). The incidence rate of PTLD was 0.26 per 100-person years in EBV D+/R+ compared to 0.33 per 100-person years in EBV D-/R+, p= 0.073. EBV D+ status was not associated with increased hazard of death in both univariable (crude hazard ratio [HR] of 1.05; confidence interval [CI], 0.98-1.11; p=0.15) and multivariable analyses (adjusted HR of 0.96; 95% CI, 0.90-1.02; p=0.14), after controlling for donor age, CMV D+ status, and the following recipient factors: age, sex, race, insurance, pre-transplant life support, pre-transplant malignancy, rejection, and graft failure. EBV D+ status was associated with decreased hazard of PTLD when adjusting for recipient age and graft failure (adjusted HR of 0.74; 95% CI, 0.56-0.98; p=0.03). In subgroup analyses by organ, EBV D+ status was associated with decreased hazard of PTLD in lung (adjusted HR of 0.56; 95% CI, 0.40-0.78; p=0.001) but not in heart transplant recipients (adjusted HR of 1.18; 95% CI, 0.71-1.96; p =0.50) (Figure 2).Figure 2.Kaplan-Meier PTLD-free survival plots for EBV D-/R+ (solid line) versus EBV D+/R+ (dashed line) post heart (red line) and lung (blue line) transplantation Conclusion Among EBV-seropositive TOT recipients, EBV D- status may be associated with increased risk of PTLD, particularly in lung transplant recipients. Disclosures Alissa J. Inc, MD, MSc, Takeda: Honoraria Sara Belga, MD, MPH, Takeda, Moderna, AstraZeneca, GSK: Advisor/Consultant|Takeda, Moderna, AstraZeneca, GSK: Grant/Research Support|Takeda, Moderna, AstraZeneca, GSK: Honoraria

Improved Outcomes and Resource Use With Normothermic Machine Perfusion in Liver Transplantation

Normothermic machine perfusion (NMP) has been shown to reduce peritransplant complications. Despite increasing NMP use in liver transplant (LT), there is a scarcity of real-world clinical experience data. To compare LT outcomes between donation after brain death (DBD) and donation after circulatory death (DCD) allografts preserved with NMP or static cold storage (SCS). This single-center, retrospective observational cohort study included all consecutive adult LTs performed between January 2019 and December 2023 at the Mayo Clinic in Arizona. Data analysis was performed between February 2024 and June 2024. Outcomes of DBD-SCS, DBD-NMP, DCD-SCS, and DCD-NMP transplants were compared. DBD and DCD livers preserved on NMP or SCS. The primary outcomes were early allograft dysfunction (EAD), intraoperative transfusion, and post-LT hospital resource use, including length of stay (LOS) and readmissions. Secondary outcomes included acute kidney injury (AKI) and 1-year graft and patient survival. A total of 1086 LTs were included in the following 4 groups: DBD-SCS (n = 480), DBD-NMP (n = 63), DCD-SCS (n = 264), and DCD-NMP (n = 279). Among LT recipients, median (IQR) age was 60.0 years (52.0-66.0); 399 LT recipients (36.7%) were female. DCD-NMP had the lowest EAD rate (17.5%), followed by DCD-SCS (50.0%), DBD-NMP (36.8%), and DBD-SCS (27.3%) (P < .001). DCD-NMP had the lowest intraoperative transfusion requirement compared to all other groups. Hospital and intensive care unit (ICU) LOS were shortest in DCD-NMP (median [IQR] hospital LOS, 5.0 days [4.0-7.0]; P = .01; median [IQR] ICU LOS, 1.5 days [1.2-3.1]; P = .01). One-year cumulative readmission probability was 86% lower for DCD-NMP vs DCD-SCS (95% CI, 0.09-0.22; P < .001) and 53% lower for DBD-NMP vs DBD-SCS (95% CI, 0.26-0.87; P < .001). AKI events were lower in DCD-NMP (31.1%) vs DCD-SCS (47.4%) (P = .001). Compared to SCS, the NMP group had a 78% overall reduction in graft failure (hazard ratio [HR], 0.22; 95% CI, 0.10-0.49; P < .001). For those receiving DCD allografts, the risk reduction was even more pronounced, with an 87% decrease in graft failure (HR, 0.13; 95% CI, 0.05-0.33; P < .001). NMP was significantly protective from patient mortality vs SCS (HR, 0.31; 95% CI, 0.12-0.80; P = .02). In this observational high-volume cohort study, NMP significantly improved LT clinical outcomes and reduced hospital resource use, especially in DCD allografts. NMP may enhance access to LT by addressing the challenges historically linked with DCD liver use.

P-2291. Low-level CMV Viremia After Solid Organ Transplant: Should We Treat?

Abstract Background Cytomegalovirus (CMV) disease is known to affect morbidity and mortality after solid organ transplant (SOT). However, less is known concerning low-level CMV viremia (llCMV) (&amp;lt; 1000 IU/ml). Having llCMV and the decision to treat llCMV with antivirals may be associated with changes in long-term graft outcomes and mortality in SOT. We aimed to review patient-level outcomes of llCMV after SOT in our large urban academic medical center. Methods We performed a retrospective review of patients from Montefiore Medical Center who underwent heart, liver, lung, kidney, pancreas, or multi-visceral transplant between 2020-2021 and developed llCMV within 2 years of SOT. Chart review was performed to characterize how llCMV was managed and outcomes such as graft failure, graft rejection, rehospitalization, concomitant infections, and death relative to llCMV detection.Figure 1.Distribution of other infections affecting solid organ transplant recipients within 1 year of low level CMV viremia. Results Eighty-five adult SOT recipients who had CMV viral loads measured between 50 and 1000 IU/mL within two years of transplant were identified. See Table 1 for recipient details. The average time from transplant to llCMV was 272 days. Seventeen (20%) patients were receiving antiviral prophylaxis at the time of llCMV, while post-transplant CMV prophylaxis had been discontinued in 66 patients (78%) for an average of 149 days prior to llCMV. 64% (54/85) were started on antivirals or had an antiviral dose increase in response to llCMV, which was continued for an average of 109 days. Within a year of llCMV, 42 (49%) of SOT recipients were re-hospitalized. Forty-two (49%) of patients experienced non-CMV infections within 1 year of llCMV detection; see Figure 1. Graft rejection occurred in 25 (29%) of patients with llCMV, and 13 (15%) experienced graft failure. Mortality within 1 year of llCMV was 8% (7/85). Conclusion llCMV is likely a reflection of overall immune status and is often temporally associated with rehospitalization and concomitant infections. Graft rejection and death are uncommon in adult SOT recipients with llCMV within 2 years of transplant. Although antiviral use was common in response to llCMV, the benefit of this is unknown and comparison to outcomes of SOT recipients without llCMV or those not receiving therapy for llCMV is needed to better determine when treatment is needed. Disclosures All Authors: No reported disclosures

P-2313. Multinational, Retrospective Study Assessing Outcomes and Healthcare Resource Utilization in Hematopoietic Stem Cell Transplant Recipients with Cytomegalovirus Infection and Refractory, Resistance, or Intolerance to Anti-Cytomegalovirus Treatments: Analysis of Impact of Viremia Clearance on Outcomes

Abstract Background Cytomegalovirus (CMV) infection is a risk factor for morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. This real-world analysis describes the impact of viremia clearance on outcomes in HSCT recipients with refractory, resistant or intolerant (RRI) CMV infection to anti-CMV agents. Methods This multicenter, retrospective chart review study included adult HSCT recipients with RRI CMV infection. Data between 2014 and 2021 were collected from 14 centers in Europe and the USA. The analysis descriptively compared demographics, patient characteristics, clinical outcomes, and hospitalizations in patients who did versus did not achieve viremia clearance during the first RRI CMV episode. Results Among 247 patients with a first RRI CMV episode, 145 (59%) achieved viremia clearance and 102 (41%) did not. In patients with vs without viremia clearance, respectively, median age was 53 vs 60 years, and 46% vs 58% were male. Of the 145 and 102 first RRI CMV episodes with vs without viremia clearance, respectively, 52% vs 75% were identified as refractory, 61% vs 31% as intolerant, and 3% vs 9% as resistant (categories not mutually exclusive); 9% vs 15% of patients developed tissue invasive disease. CMV recurrence occurred in 35% vs 37% and graft failure in 3% vs 6% of patients with vs without viremia clearance, respectively (Table). Myelosuppression and nephrotoxicity events during CMV episodes were reported in 54% vs 44% and 26% vs 27% of patients with vs without viremia clearance, respectively (Table). CMV-related hospitalizations with/without emergency department visits occurred in 35% of patients with viremia clearance vs 43% of patients without viremia clearance (Table). Notably, the overall mortality within 1 year of RRI identification in patients without viremia clearance was higher than in those with viremia clearance (68% vs 30%, respectively). Conclusion These results highlight the high disease burden in HSCT recipients with RRI CMV infection. In this difficult-to-treat population, the mortality rate was higher in patients without viremia clearance than in patients with viremia clearance. Disclosures Kimberly Davis, RPh, MS, Takeda: Employee|Takeda: Stocks/Bonds (Public Company) Ines Mendonça, MSBiostats, CTI Clinical Trial &amp; Consulting Services: Employee (paid to provide consulting services including medical writing and statistical analysis) Tien Bo, PharmD, Takeda: Employee|Takeda: Stocks/Bonds (Public Company)

P-1033. Post-transplant Outcomes in Kidney Transplant Recipients with Invasive Fungal Infections Prior vs. After the Emergence of SARS-CoV2

Abstract Background Invasive fungal infections (IFIs) are a serious complication in kidney transplant recipients (KTRs), leading to increased mortality and graft failure. Given changes in care associated with pandemic conditions and potential compounding effects of COVID-19 infection, we sought to determine whether the emergence of SARS-CoV2 contributed to a rise in adverse transplant outcomes associated with IFIs. Methods We performed a retrospective study of adult KTRs transplanted at Johns Hopkins from 2012-2018 with follow up through 5/2023. IFI diagnoses were based on EORTC/MSGERC criteria. If a patient had more than one IFI, the date of first IFI served as the index exposure. KTRs with and without IFIs were matched 1:1 on time-post-KT. We followed patients until all-cause graft loss (ACGL), a composite outcome of graft failure and mortality, and estimated cumulative incidence of ACGL prior vs. after emergence of SARS-CoV2 in 2/2020. We then determined whether the association between IFI and ACGL varied before vs during SARS-CoV2 pandemic using Cox regression with an interaction term and adjusting for age, transplant risk, and cardiovascular disease.Table 2.First post-transplant invasive fungal infection among kidney transplant recipients prior vs. post emergence of SARS-CoV2 Results Among 1453 KTRs, 79 (5.4%) had proven/probable IFIs of which 12 occurred after emergence of SARS-CoV2 (Table 1). Yeast caused the majority of IFIs (50/79) over the study period, but mold (5/12) and yeast (6/12) were equally represented among IFIs occurring after the emergence of SARS-CoV2 (Table 2). Prior to the pandemic, ACGL occurred in 66% (44/67) of KTRs with IFIs compared to 31% (414/1338) of KTRs without IFIs (log-rank p &amp;lt; 0.001). During the pandemic, ACGL occurred in 75% (9/12) of KTRs with IFIs compared to 31% of KTRs without IFIs (log-rank p &amp;lt; 0.001) (Fig 1). KTRs with IFIs had a 2-fold greater risk of ACGL (aHR 2.05, 95% CI 1.17-3.57, p = 0.012) prior to the pandemic and a 5.5-fold greater risk of ACGL (aHR 5.54, 95% CI 1.17-26.24, p &amp;lt; 0.01) during the pandemic. The risk of ACGL associated with IFIs was significantly different after the emergence of SARS-CoV2 (p-interaction term &amp;lt; 0.001; Fig 2).Figure 1.ACGL-free survival of KTR with IFIs vs. without IFIs Conclusion KTRs with IFIs had higher rates of ACGL during the pandemic, and molds constituted a greater proportion of the IFIs during the pandemic. The emergence of SARS-CoV2 seems to have shifted the epidemiology of IFIs among KTRs, leading to increased ACGL.Figure 2.ACGL-free survival of KTR with IFIs prior vs. after emergence of SARS-CoV2 Disclosures Nitipong Permpalung, MD, MPH, CareDx: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|ClearView: Advisor/Consultant|IMMY Diagnostics: Grant/Research Support|Merck: Grant/Research Support|Pearl Diagnostics: Grant/Research Support|Pulmicide: Advisor/Consultant|Scynexis: Grant/Research Support

Taming the transplant troll: Exploring racial and ethnic disparities in cytomegalovirus infection among kidney transplant patients.

Cytomegalovirus (CMV) infection poses a significant risk to kidney transplant recipients. This study investigated CMV disease incidence, outcomes, and management challenges in racial and ethnic minority populations following kidney transplantation. This single-center, mixed-methods study included a retrospective cohort analysis of kidney transplant recipients (n = 58) and qualitative surveys of healthcare providers. Patients were categorized as minorities (n = 49) or non-Hispanic whites (n = 9). The primary outcome was CMV disease incidence. Secondary outcomes included graft failure, mortality, and identification of management barriers. The cumulative incidence of CMV disease was higher in minorities than in non-Hispanic whites (12.3% vs. 0%, p = 0.58), although the difference was not statistically significant. All graft failures (8.6%, n = 5) occurred in the minority group. Although not statistically significant, all-cause mortality was higher in the minority group (24.5% vs. 11.1%, p = 0.54), with 46.2% of the deaths occurring within 90 days of CMV diagnosis. Qualitative analysis revealed challenges in diagnosis, treatment-related side effects, medication costs, and insurance barriers. The providers emphasized the importance of interdisciplinary collaboration and standardized protocols. While limited by the small sample size, this study highlights potential disparities in the incidence and outcomes of CMV disease among minority kidney transplant recipients, suggesting that barriers in care and access may contribute to these differences. These hypothesis-generating findings underscore the need for larger multicenter studies to validate these patterns and to inform targeted strategies that may reduce inequities in post-transplant outcomes.

P-2261. Belatacept-based immunosuppression does not confer increased risk of BK Polyomavirus -DNAemia relative to Tacrolimus-based immunosuppression

Abstract Background BK polyoma virus (BKPyV) DNAemia imparts significant morbidity in kidney transplant recipients (KTR). It can lead to polyomavirus-associated nephropathy (PyVAN), impaired graft function, and graft failure. The effect of belatacept on BK polyoma virus (BKPyV) control remains largely unknown. Methods This is a propensity matched retrospective cohort study in adult kidney transplant recipients (KTR) transplanted between 2016-2020 who received a belatacept- versus tacrolimus-based immunosuppression regimen. A multi-state Markov model was used to evaluate BKPyV replication dynamics (BKPyV-dyn). Three BKPyV-dyn states were defined: BKPyV-dyn1 (viral load &amp;lt; 3 log10), BKPyV-dyn2 (viral load &amp;gt; 3 log10 and &amp;lt; 4 log10), and BKPyV-dyn3 (viral load &amp;gt; 4 log10). Estimated total length of stay in a BKPyV replication dynamic state after evolution of the entire Markov process Results 280 KTR on belatacept- and 280 KTR on tacrolimus-based regimens were compared. The probability of transitioning between BKPyV-dyn states and time spent in each state in both groups was comparable. Total duration in BKPyV-dyn-1 was 632.1 days (95%CI 612.1, 648.5) for belatacept vs 615.2 days (95% CI 592.5, 635.8) for tacrolimus, BKPyV-dyn-2 was 49.2 days (95% CI 41.3, 58.4) for belatacept vs 55.6 days (95% CI 46.5, 66.8) for tacrolimus, and BKPyV-dyn-3 was 48.7 days (95% CI 52.3, 79.5) for belatacept vs 60.9 days (95% CI 48.3, 76.4) for tacrolimus (Figure 1). Estimated mean sojourn time did (time spent in a given BKPyV-dyn state prior to transitioning to another state) did not differ by immunosuppression (Figure 2). BKPyV associated nephropathy (PyVAN) occurred in 3.9% in belatacept- and 3.9% tacrolimus-treated KRT (P &amp;gt;0.9). Estimated mean sojourn time by immunosuppression Average single occupancy time in a BKPyV replication dynamic state Conclusion Collectively, our results indicate that relative to patients on tacrolimus-based regimens, patients on belatacept-based immunosuppression regimens do not require more frequent BKPyV QNAT monitoring or more aggressive immunosuppression reduction when BKPyV-DNAemia 3 log10 or greater is detected. Disclosures Christian P. Larsen, MD, PhD, Bristol-Myers Squibb: Advisor/Consultant|CareDx: Advisor/Consultant|Eledon: Advisor/Consultant

P-1408. Beyond the Transplant: Understanding CMV Disease in Minority Kidney Recipients

Abstract Background Disparities in kidney transplant evaluation for minorities raise concerns about post-transplant care access, including cytomegalovirus (CMV) infections and their impact. While CMV significantly affects morbidity and mortality rates, the precise ramifications of these disparities remain unclear. We aimed to evaluate CMV infection patterns in minority kidney transplant recipients. Methods We evaluated CMV infection in minority kidney transplant recipients using retrospective analysis and qualitative surveys. Patients aged ≥ 18 years with post-transplant CMV infection were included. Data were collected from University of New Mexico Health Sciences Center records and provider surveys. The primary outcome was CMV disease incidence among minority populations, with secondary outcomes exploring clinical endpoints and barriers to CMV management. Quantitative and qualitative data were analyzed using descriptive statistics, chi-square and Fisher’s exact tests, and thematic analysis. Results Among 58 patients (84.5% minorities), CMV disease cumulative incidence was 12.3% in minorities vs. 0% in non-Hispanic whites (p = 0.58), despite similar prophylaxis. No significant CMV disease risk factors were found. Graft failure occurred in 8.6% of patients, mostly minorities, with one graft loss after CMV diagnosis. Mortality appeared higher in minorities (24.4% vs 11.1%, p = 0.67), especially within 90 days of CMV diagnosis, and notably elevated in diabetics (40% vs 9.1%, p = 0.01). Eight respondents (75% transplant specialists) highlighted CMV management challenges from diagnosis to resource access. Providers acknowledged limitations in current strategies and expressed optimism for newer therapies, such as letermovir. Systematic barriers, including policy gaps and suboptimal multidisciplinary collaboration, were identified as hindrances to comprehensive care delivery. Conclusion Our study underscores the CMV disease burden among minority kidney transplant recipients, highlighting disparities in incidence and clinical outcomes compared to non-Hispanic whites. Urgent interventions and policy reforms are required to address systemic barriers and improve post-transplant care equity, ultimately enhancing the health outcomes of minority transplant patients. Disclosures M. Gabriela Cabanilla, PharmD, PhC, Merck &amp; Co: Grant/Research Support

P-2282. Infectious Complications Following Lung Transplant for COVID-19 Related Respiratory Failure

Abstract Background Lung transplantation (LT) is a potentially life-saving treatment option for COVID-19 related irreversible respiratory failure. Early outcomes for 1-year survival and graft failure rates among LT recipients (LTr) for COVID-19 related respiratory failure is similar to LTr for non-COVID etiologies. However, the infectious, real-world analysis of complications following LT among LTr for COVID-19 related respiratory failure in comparison to LTr in COVID-19 unrelated respiratory failure has not been described. Our objective was to compare the post-LT infectious complications among LTr for COVID-19 related and unrelated respiratory failure. Methods We analyzed all consecutive LT done at Henry Ford Health System from January 2020 to October 2023. All patients received standard antimicrobial prophylaxis. Demographic data was obtained. The primary outcome was the rate of any infectious complication within one year from transplantation. Secondary outcomes were rates of specific infections, time to infection, and all-cause mortality at 30 days, 90 days, and 1- year. Results A total of 98 lung transplantations were done at our center from January 2020 to October 2023. COVID-19 related LTr accounted for 11% of transplants. Median time of follow up was 365 days (187-365). COVID-19 related LTr were younger (median 53 vs. 64 years [p 0.02]) and predominantly white race (p &amp;lt; 0.01). Comorbidities amongst both groups were similar. Rates of post-LTr infectious complications were similar among the two groups, 66% overall. Time to first infection was shorter in the COVID-19 related LTr cohort, however this did not reach significance. Pleuropulmonary infections predominated overall (47%). All-cause post-LT mortality was similar in both groups (Table 1). Conclusion Patients receiving LT for COVID-19 related respiratory failure have similar, high rates of infectious complications compared to patients with non-COVID-19 related etiologies, but mortality remains low. LT for COVID-19 related respiratory failure is an acceptable modality of treatment. Disclosures Mayur Ramesh, MD, AstraZeneca: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant