Adult Kidney Transplant Recipients Research Articles

A Phase I Study Evaluating Safety and Tolerability of Viral-Specific T Cells Against BK-Virus in Adult Kidney Transplant Recipients.

BK polyomavirus (BKPyV) poses a significant threat to kidney transplant recipients (KTR). Current management primarily involves reducing immunosuppression, which increases the risk of rejection. Cell-based immunotherapy with virus-specific T cells (VST) has emerged as an alternative approach for treating BKPyV in KTRs. This single-center phase I, open-label trial enrolled KTRs with persistent BKPyV-DNAemia and BKPyV nephropathy (BKPyVAN) (NCT05042076) despite being on lower immunosuppression. BK-specific T cells were isolated from leukapheresis products from compatible donors. Patients were treated with VST therapy and followed for 52 weeks. Safety and tolerability were the primary focus of this trial. Three patients completed the trial. No grade III or IV adverse events, acute rejections, or graft versus host disease were reported. All patients tolerated the therapy well, with no significant safety concerns observed during the follow-up period. BK-VST demonstrated promising safety and tolerability profiles in this small cohort of kidney transplant recipients with severe BK infections. These findings suggest that VST therapy may offer a safe adjunctive treatment option for BKPyV infections post-transplantation. Larger studies are needed to confirm these preliminary results and assess long-term efficacy in treating BKPyV infections and preserving graft function in kidney transplant recipients.

Long-Term Outcomes of Belatacept Versus Tacrolimus Following T-Cell Depleting Induction in Adult Kidney Transplantation.

Belatacept shows promise as an alternative immunosuppressant without the nephrotoxicity of calcineurin inhibitors. Avoiding nephrotoxicity is important with the expanding use of organs at risk of marginal graft function. To date, no large studies have compared belatacept directly with tacrolimus after T-cell depleting induction in renal transplantation. The Standard Transplant Analysis and Research file was used to compare adult kidney transplant recipients induced with T-cell depleting agents treated with belatacept to propensity score-matched recipients treated with tacrolimus between August 10, 2011 and June 29, 2023. Kaplan-Meier survival analysis was used to compare death censored graft survival, patient survival, and time to acute rejection. During the study period, 4391 adult kidney transplant recipients were treated with belatacept. Estimated GFR improved for belatacept-treated patients through year 9, whereas it decreased for the control group through year 10. Belatacept-treated patients had a higher rejection rate at 5 years (21%vs. 15%, p <0.001). Death-censored graft survival did not differ between groups (p = 0.383). Among patients who had rejection, death-censored graft survival was superior in belatacept-treated patients at 5 years (70%vs. 60%, p = 0.026). Overall, patient survival did not differ between groups (p = 0.120). This is the largest longitudinal study to compare outcomes of belatacept versus tacrolimus-based therapy following T-cell depleting induction. Belatacept was associated with improved graft function despite an increased acute rejection rate. There was no difference in overall graft or patient survival compared to tacrolimus. This study suggests that belatacept-based therapy is not inferior to tacrolimus-based therapy following T-cell depletion.

Ambulance Service Utilization by Kidney Transplant Recipients.

Compared with the general population, kidney transplant recipients (KTRs) frequently visit the emergency department (ED), but much less is known about the characteristics of ED presentations requiring ambulance transport and the impact on subsequent outcomes for KTRs. To identify predictors of ambulance transport to the ED (ambulance-ED) and outcomes (graft failure and mortality) for those who experienced an ambulance-ED event in a cohort of KTRs. Retrospective cohort study of incident, adult KTRs receiving a transplant from 2008 to 2020. Nova Scotia, Canada. Adult (≥18 years), Nova Scotian KTRs affiliated with the Atlantic Canada Multi-Organ Transplant Program. Ambulance-ED events were captured for all transplant recipients (following the day of discharge from their initial transplant admission) using electronic records (provided by Emergency Health Services, the sole provider of emergency medical services for Nova Scotia). Ambulance-ED was defined as ambulance transport to the ED following a 911 call; interfacility transfers were excluded. Predictors of ambulance-ED included recipient, donor, immunological, and perioperative characteristics (pertaining to the initial admission for kidney transplantation). Outcomes included graft failure and mortality. Predictors of ambulance-ED were analyzed using a multivariable negative binomial regression model and reported using incidence rate ratios (IRRs) and 95% confidence intervals (CIs). The risk of death/graft failure for those with an ambulance-ED within 30 days of hospital discharge following transplantation was analyzed using an adjusted Cox survival analysis and reported using hazard ratios (HRs) and 95% CIs. A total of 418 patients received a transplant during the study period. A total of 179 (42.8%) experienced one or more ambulance-ED events. Female sex (IRR = 1.60; 95% CI = 1.12-2.29), kidney failure secondary to diabetes (IRR = 2.52; 95% CI = 1.19-5.31), and donor age ≥45 (IRR = 1.50; 95% CI = 1.04-2.15) were all associated with ambulance-ED. There was no significant increase in the risk of death/graft failure for those that experienced ambulance-ED within 30 days of hospital discharge following transplantation (HR = 1.31; 95% CI = 0.44-3.94). A limitation of this study was that ambulance-ED is not a perfect surrogate marker of acute care needs in a population. Important determinants of health such as living situation and socioeconomic status were not available in this data set. This study highlights the burden of ambulance use for KTRs and provides insight into the need for more optimal follow-up in certain patient subgroups who are at particularly high risk.

Impact of intraoperative desmopressin on postoperative urine output in adult cadaveric kidney transplantation: a single-centre retrospective cohort study.

Desmopressin, a synthetic analogue of vasopressin, is used to prevent uremic bleeding in patients undergoing kidney transplantation but can cause oliguria. Graft function assessment is crucial after kidney transplantation. Urine output (UOP) is the simplest, most feasible, and most cost-effective perioperative monitoring tool to assess graft function in kidney transplantation. No study, to our knowledge, has yet assessed this association in the setting of cadaveric adult kidney transplantation. We conducted a retrospective single-centre cohort study to evaluate the impact of desmopressin on UOP in the immediate postoperative period after kidney transplantation at a tertiary care academic hospital in Baltimore, MD, USA. We included a total of 938 adults who received a cadaveric kidney transplant from January 2016 to December 2022 in the study after reviewing selection criteria. As the primary outcome, we compared immediate postoperative UOP (mL·kg-1) between recipients of desmopressin and nonrecipients of desmopressin. The secondary outcomes of the study were UOP at 12 and 24hr postoperatively, estimated blood loss (EBL), and postoperative hemoglobin. Three hundred and fifty-nine (38%) patients received desmopressin intraoperatively. Using multivariable linear regression, desmopressin use was associated with 0.6mL·kg-1 lower UOP, representing an average 19% reduction in UOP from a mean UOP of 3.1mL·kg-1 in the operating room after adjusting for confounders. A similar reduction in 12- and 24-hr postoperative UOP was also noted (3mL·kg-1 and 6mL·kg-1, respectively), while desmopressin was associated with a slightly higher EBL. We also observed a dilutional reduction in postoperative hemoglobin. Intraoperative desmopressin in adult cadaveric kidney transplant recipients was associated with reduced urine output in the postoperative period without any significant hemostatic benefit.

Combination Automated Microfluidics Measurement of Urine CCL2, CXCL9, CXCL10 and VEGF-A for Monitoring Patients with a Kidney Transplant.

Recent studies indicate that up to 36% of pediatric and adult kidney transplant recipients with stable serum creatinine levels will have acute rejection detected on surveillance biopsy. The purpose of this study was to develop and validate a risk algorithm for identifying low- and high-risk patients using a novel automated platform that simultaneously measures urinary CCL2, CXCL9, CXCL10 and VEGF-A with high precision. We designed a multicenter observational study to evaluate the performance of urinary CCL2, CXCL9, CXCL10 and VEGF-A in a training set of 517 banked samples collected at the time of surveillance or indication kidney biopsies from both adult and pediatric recipients. Risk algorithms combining all four analytes were developed in the training set, and subsequently validated in three laboratory sites in two additional pediatric cohorts (N=174). The automated platform had remarkably high throughput, generating reproducible results in 60-70 minutes. Analysis was initially performed in the training set (N=517), which included biopsies read as normal (N=330), acute rejection (N=92) or borderline rejection (N=95). We found that each biomarker independently discriminated normal biopsies vs. those with acute rejection (P < 10-5). A risk algorithm utilizing all four biomarkers (score4) had excellent diagnostic performance for acute rejection in both for-cause and surveillance biopsies performed on patients with stable GFRs, outperforming any individual biomarker as well as estimated GFR assessments. Validation assays performed in the two additional pediatric cohorts in three laboratory sites demonstrated a robust correlation of results; score4 retained excellent diagnostic performance (75% specificity and 92% negative predictive value). Automated measurements of urine CCL2, CXCL9, CXCL10 and VEGF-A can distinguish kidney transplant recipients at low- vs. high-risk for rejection. We suggest that this assay can advantage clinical decision-making in routine post-transplant monitoring due to its low cost, rapid throughput, and operator independence.

Risk of Cytomegalovirus Viremia Following Transplantation of Hepatitis C-Viremic Donor Kidneys Into Uninfected Recipients: A Multi-Center Retrospective Cohort Study.

Several studies have suggested an increased risk of cytomegalovirus (CMV) viremia among Hepatitis C virus (HCV)-uninfected recipients of kidney transplants from HCV-RNA+ deceased donors (HCV D+/R-), but these studies featured small sample sizes and limited ability to address confounding variables. We assembled a retrospective cohort of adult kidney transplant recipients at five US centers between 4/1/2015 and 12/31/2020 to determine the association between HCV D+/R- transplants and the outcomes of CMV viremia (>1000 IU/mL), death-censored graft failure, and mortality in the first posttransplant year compared to HCV D-/R- transplants. We generated highly similar matched cohorts of HCV D+/R- and HCV D-/R- recipients based on attributes that affect the risk of CMV viremia. We matched exactly on center, CMV donor/recipient serostatus, and antibody induction therapy. The cohort comprised 275 HCV D+/R- recipients with a mean age of 52.5 years (SD = 10.7); 19% were CMV D+/R-, and 74% received anti-thymocyte globulin induction. With variable ratio matching, 267 HCV D+/R- recipients were matched to 996 HCV D-/R- recipients. CMV viremia occurred in 15% of HCV D+/R- and 11% of HCV D-R- recipients. In Cox regression, transplantation with an HCV-RNA+ donor kidney was not associated with a significantly higher risk of CMV viremia (HR 1.3, 95% CI 0.89-1.92) or death-censored graft loss (HR 0.61, 95% CI 0.31-1.2). The risk of CMV viremia was not significantly increased among HCV D+/R- kidney recipients. Future studies should examine associations between donor-derived HCV infection and clinical outcomes of CMV syndrome and disease.

Quantifying Gamma-Interferon from CMV-Specific CD8+ T Cells Defines Protection Against Clinically Significant CMV Infection in Solid Organ Transplant Recipients: The Quanti-CMV Score.

The cutoff value of the commercial interferon (IFN)-γ release assay (QuantiFERON-CMV) proposed by the manufacturer is assumed to be predictive. We aimed to determine the optimal cutoff value for protection against clinically significant cytomegalovirus (CMV) infection within 30 days. We analyzed two different cohorts: adult CMV seropositive kidney transplant (KT) recipients with antithymocyte globulin (ATG) induction from the TIMOVAL study and seropositive lung transplant (LT) patients from the CYTOCOR study. The optimal cutoff value was established using Youden's index. We estimated the predictive capacity of the cutoff value through the AUROC and assessed the diagnostic accuracy of the assay at the different cutoff values. We finally evaluated clinical variables that could improve the predictive ability of the assay on a predictive score. Four hundred-four samples from 130 transplant recipients were analyzed. The optimal cutoff value was ≥2.2 IU/mL for both populations, with a positive predictive value of 99% and 99.5% (95% CI, 98-100%) for KT and LT recipients, respectively. The AUROC of the predictive score was 0.85 (95% CI, 0.73-0.97). Using the proposed cutoff value and the Quanti-CMV score may allow the individualization of preventive strategies and serve as an objective tool to support clinical decision-making.

Increased ferritin levels are associated with incident diabetes after kidney transplantation: A prospective cohort study.

Iron is known to play a role in glucose homeostasis, and diabetes is highly prevalent in patients with iron overload. Here, we investigated whether ferritin and hepcidin (as parameters of iron status) are associated with the development of post-transplant diabetes in kidney transplant recipients, a population in which around 10 % is known to have high iron status. Prospective data from the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study from the University Medical Center Groningen, the Netherlands were evaluated, involving stable adult kidney transplant recipients > 1 year after transplantation. Associations between ferritin and hepcidin levels, as markers of iron status, and incident post-transplant diabetes were analyzed by multivariable Cox regression models, followed by the exploration of potential clinical cut-offs of ferritin levels related to the risk of post-transplant diabetes. Of the included 443 kidney transplant recipients (age 50 ± 12 years, 44 % women, median 6.1 [3.0 - 12.1] years after transplantation), 65 kidney transplant recipients (15 %) developed post-transplant diabetes during a median follow-up of 9.6 [6.3 - 10.2] years. In contrast to hepcidin levels, ferritin levels were significantly associated with incident post-transplant diabetes, independent of adjustment for potential confounders (HR per 50 µg/l, 1.08; 95 % CI 1.02 - 1.14). When analyzing specific clinical cut-offs of ferritin levels, kidney transplant recipients with a ferritin > 500 µg/l (n=40) had more than twice the risk of developing post-transplant diabetes, compared to kidney transplant recipients with ferritin < 100 µg/l (HR, 2.81; 95 % CI 1.04 - 7.55). Increased levels of ferritin are independently associated with a higher risk of post-transplant diabetes in kidney transplant recipients. Especially, kidney transplant recipients with ferritin levels > 500 µg/l, seem susceptible to the development of post-transplant diabetes over time.

Association of glucagon-like peptide-1 receptor agonists with cardiovascular and kidney outcomes in type 2 diabetic kidney transplant recipients

BackgroundCardiovascular disease is a leading cause of post-transplant mortality in kidney transplant recipients (KTRs), especially those with diabetes. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and kidney benefits in the general population with type 2 diabetes mellitus (T2DM), evidence regarding their effects in diabetic KTRs is limited.MethodsThis retrospective cohort study utilized data from the Global Collaborative Network in TriNetX, spanning January 1, 2006, to June 1, 2023. Propensity score matching (PSM) with 1:1 ratio was employed to create balanced cohorts. Adult KTRs with T2DM who received GLP-1 RAs within 3 months post-transplant were compared to a matched cohort of KTRs who did not. The primary outcome was all-cause mortality, with secondary outcomes including major adverse cardiovascular events (MACEs) and major adverse kidney events (MAKEs).ResultsA total of 35,488 adult KTRs with T2DM (mean [SD] age, 57.7 [12.2] years; 57.7% men) were identified and 9.8% patients used GLP-1 RAs among 3 months post-transplant. Following PSM, 3564 GLP-1 RAs users were matched with an equal number of nonusers. After a median follow-up of 2.5 years, GLP-1 RAs users had lower risks of mortality (adjusted hazard ratio (aHR), 0.39; 95% CI 0.31–0.50), MACEs (aHR 0.66; 95% CI 0.56–0.79), and MAKEs (aHR 0.66; 95% CI 0.58–0.75). Adverse effects included higher risks of nausea, vomiting and diarrhea, while risks of suicide, hypoglycemia, retinopathy, and pancreatitis were not increased.ConclusionsIn KTRs with T2DM, GLP-1 RAs use was associated with substantial reductions in all-cause mortality, MAKEs, and MACEs compared to nonuse without increasing complications. However, the underutilization of GLP-1 RAs represents a significant opportunity to improve post-transplant outcomes in this high-risk population.Graphical abstract

Glucagon-Like Peptide 1 Receptor Agonists and Renal Outcomes in Kidney Transplant Recipients with Diabetes Mellitus.

Glucagon-Like Peptide 1 Receptor Agonists and Renal Outcomes in Kidney Transplant Recipients with Diabetes Mellitus.

Retrospective analysis of tacrolimus concentrations and factors influencing their levels in adult kidney transplant recipients treated with Dailiport

Retrospective analysis of tacrolimus concentrations and factors influencing their levels in adult kidney transplant recipients treated with Dailiport

Secular trends in cytomegalovirus (CMV) risk and outcomes: results from a 10-year longitudinal cohort study in adult kidney transplant recipients.

The goal of this study was to determine the secular trends in the incidence of CMV sero-mismatch (D+/R -) and if these trends meaningfully impact clinical outcomes. This was a single-center longitudinal cohort study in adult kidney recipients transplanted between Jan 2012 and June 2021 with follow-up through June 2022. Baseline and follow-up data were collected. Univariate and multivariate statistics were used to analyze the data. 2,392 kidney transplants were performed during the study period; 132 patients did not meet inclusion criteria. The mean age was 52years, 41% were female, 57% were black, and 19% were CMV D + /R -. The odds of being CMV high-risk increased by 6% each year (OR 1.06, 1.02-1.10 p = 0.003); 48% of the variability associated with CMV serostatus was explained by transplant year (R2 = 0.478, p = 0.002). Sequential modeling demonstrated that CMV D + /R - serostatus was a substantial risk factor for CMV infection (HR 5.7, 4.5-7.3), CMV disease (HR 8.4, 3.9-18.0), CMV resistance (HR 17.9, 3.8-84.2), CMV refractory infection (HR 35, 4-280), late CMV infection (HR 12.0, 8.3-17.1), acute rejection, and hospitalization for opportunistic infections. Secular trend analysis demonstrated that CMV infections, CMV resistance, and late CMV increased in incidence since 2012. The risks of CMV resistance and late infection was significantly influenced by D + /R - serostatus and transplant year, indicating that this risk is worsening over time. The CMV D + /R - serostatus remains the single most important risk factor for CMV infection, disease, resistance, refractory infection, and late CMV, which appears to be increasing in magnitude.

Induction outcomes in adult kidney transplantation: Two decades of UNOS data analysis.

Induction outcomes in adult kidney transplantation: Two decades of UNOS data analysis.

Interventions to Improve Life Participation in Kidney Transplant Recipients: A Systematic Review.

Life participation, defined as the ability to participate in meaningful activities of daily living, is a critically important outcome for kidney transplant recipients. We aimed to evaluate the effectiveness of any interventions on life participation in kidney transplant recipients. A systematic review of randomized controlled studies. Adult kidney transplant recipients. MEDLINE, Embase, CENTRAL, PsycINFO and CINAHL were searched up to March2023. Two authors independently screened titles and abstracts, and extracted data from the included studies using standard data extraction forms. We used random-effects models with relative risk for dichotomous outcomes and mean difference for continuous outcomes with 95% confidence intervals (CIs). Confidence in the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. From 14,162 reports, only 33 studies (4,857 participants) were included. The risk of bias was adjudicated as high or unclear for most domains. No studies reported the outcome of life participation specifically. Among 33 studies, mental, physical and social functioning were reported in 5 (15%), 5 (15%), and 11 (33%) studies, respectively. A wide range of interventions were included across the studies with a limited follow-up, and we were unable to pool the data and perform meta-analysis for outcomes that were reported in a single study only or in studies reporting no events. The effects of prebiotics, erythropoietin-stimulating agents, immunosuppressive treatments, induction therapy of interleukin-2 receptor antagonist, exercise, nutrition, education, and surgical procedures on life participation-related outcomes were uncertain. Life participation was not reported as a specific outcome in trials in kidney transplant recipients with very limited evidence on interventions for life participation-related outcomes. Trial-based evidence for interventions to improve life participation, a critical outcome for kidney transplant recipients, is needed.

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

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

592. Immunogenicity and Safety of High-dose versus Double-dose Quadrivalent Inactivated Influenza Vaccine in Adult Kidney Transplant Recipients: A Randomized Controlled Trial

Abstract Background Both high-dose and double-dose inactivated influenza vaccines have been shown to better elicit a greater immune response compared to standard-dose influenza vaccine in solid organ transplant (SOT) recipients. However, a direct comparison between high-dose (HD) and double-dose (DD) quadrivalent inactivated influenza vaccine (QIIV) has not been explored. Methods From June to December 2023, we conducted an open-label randomized controlled trial to compare the immunogenicity and safety of the 2023 southern hemisphere HD QIIV at 60 ug (Effluelda, Sanofi) versus double standard-dose QIIV at 30 ug (Fluarix tetra, Sanofi) in adult kidney transplant (KT) recipients. Pre-immunization and 4-week post-immunization sera underwent strain-specific hemagglutination inhibition assays, and safety profiles were assessed. Results Eighty-four eligible KT recipients were randomly assigned to receive either HD QIIV or DD QIIV (42 each). Among them, 50 (59.5%) were male, with a mean age (SD) of 46 (11) years old, and 50 (60.7%) participants received kidneys from deceased donors. Common immunosuppressive regimens included mycophenolate mofetil (65.5%), tacrolimus (77.1%), and prednisolone (100%). SC to at least 1 strain was significantly greater in the HD QIIV group (95.2%) compared to the DD QIIV group (69%) (P = 0.006). The SC rate for A/H1N1, A/H3N2, B/Victoria, and B/Yamagata strains was higher in the HD QIIV group compared to the DD QIIV group, with the following percentages: 69.1% vs 52.4%, 52.4% vs 38.1%, 52.4% vs 42.9%, and 61.9% vs 40.5% (P = 0.118, P = 0.188, P = 0.382, and P = 0.049, respectively). In multivariate analysis, SC to at least 1 vaccine strain was significantly associated with the use of HD vaccine (OR 17.59, 95% CI [2.10, 147.22], P=0.008) and receiving the vaccine after 1-year post-KT (OR 34.76; 95% CI [2.59–454.45], P=0.007). There were significantly fewer occurrences of pain at the injection site and muscle ache in the HD QIIV group compared to the DD QIIV group, with the following percentages: 4.8% vs 19.0%, and 0% vs 9.5% (P = 0.040 and P = 0.043, respectively). Conclusion HD QIIV could marginally elicit a more pronounced immune response, alongside a comparatively reduced occurrence of adverse reactions, in adult SOT recipients when compared with DD QIIV. TCTR20230510005. Disclosures All Authors: No reported disclosures

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

Healthcare Resource Utilization Associated with Leukopenia and Neutropenia in Kidney Transplant Recipients Receiving Valganciclovir in the United States.

Background: Cytomegalovirus prophylaxis in kidney transplant recipients (KTRs) is limited by post-transplant neutropenia and leukopenia (PTN/PTL). Despite its clinical significance, the healthcare resource utilization (HCRU) related to PTN/PTL remains poorly characterized. Objective: To evaluate HCRU among KTRs taking valganciclovir during their first year post-transplant. Methods: Using TriNetX Dataworks-USA, a federated, de-identified electronic medical record database, we identified adult KTRs who underwent their first kidney transplant from January 2012 to September 2020. All eligible patients were followed for 1 year. PTN/PTL was defined as absolute neutrophil count less than 1000/μL or white blood cell count less than 3500/μL. Multivariable logistic/Poisson regression models were used to assess the association between PTN/PTL and various HCRU types. Results: A total of 8791 KTRs were identified, of whom 6219 (70.7%) developed PTN/PTL at a mean of 5.7 months post-transplantation. Hospitalizations, rehospitalizations, emergency room visits, outpatient appointments, packed red blood cell transfusions, and granulocyte-colony stimulating factor administration were more prevalent among KTRs with PTN/PTL (61.1% vs 49.5%, 24.5% vs 14.1%, 35.2% vs 28.9%, 30.4 vs 26.2 visits, 22.3% vs 17.6%, 23.4% vs 2.2%, respectively; P < .001). Adjusted analyses confirmed that PTN/PTL correlated with increased HCRU across all categories. Conclusions: KTRs who developed PTN/PTL had significantly higher HCRU. Further studies are needed to evaluate strategies addressing PTN/PTL for KTRs.

P-1602. Urinalysis with Reflex Urine Culture to Screen for Asymptomatic Bacteriuria in Kidney Transplant Recipients: Opportunities for Diagnostic and Antimicrobial Stewardship

Abstract Background Routine screening and treatment of asymptomatic bacteriuria (ASB) in kidney transplant recipients (KTRs) beyond 1 month post-transplant are no longer recommended due to potential harm. Evidence from clinical trials demonstrated that screening and treatment of ASB does not reduce the risk of pyelonephritis, acute rejection or long-term graft impairment. However, ASB screening post-transplant remains a common practice. This study characterizes our institution’s current practice with associated testing costs regarding screening and treatment for ASB for the first 3 months post-transplant. Estimated annual cost of urinalysis and urine culture in kidney transplant recipients at University of Washington Medical Center The estimated annual cost of urinalysis and urine culture was calculated based on the testing cost in 50 patients for the first three months post-transplant, assuming a total of 200 patients receive kidney transplant annually at our institution. The average cost of urinalysis and urine culture per person for the first three months after transplant was $1511.47. This estimate does not take into account urinalyses and urine cultures beyond three months. The estimated cost savings assume that urinalysis with reflex urine cultures is de-implemented and urine cultures are ordered only for symptomatic patients. This estimate does not consider the potential reduction in the number of urine cultures based on negative urinalysis in symptomatic patients. Methods We conducted a retrospective review of electronic records for 50 consecutive adult KTRs at University of Washington Medical Center between January and April 2023. Data collected included demographics, laboratory results, microbiological findings, antibiotic usage for 3 months post-transplant, and rejection within 1 year post-transplant. A chart review by 2 independent reviewers was performed to determine whether each positive urine culture (UCx) represents ASB or urinary tract infection (UTI). Results Among 50 KTRs, a total of 709 urinalyses (UA, mean 14.2 per person) and 263 UCx (mean 5.2 per person) were performed within 3 months post-transplant. Reflex from UA accounted for 95.4% of UCxs (251 out of 263), and 35.4% of UA were reflexed to UCx (251 out of 709). Of 40 positive urine cultures, 6 were considered symptomatic UTI and 34 as ASB. The mean cost of routine screening with UA with reflex UCx for the first 3 months after transplant was $1511.47. The estimated annual cost based on 200 KTRs per year exceeds $300,000 (Figure 1). All 6 UTI episodes and 5 of 34 ASB episodes (14.7%) were treated with antibiotics. Acute rejection by 1 year post-transplant occurred in 2 out of 50 patients (4%), but neither had ASB nor UTI within 3 months of transplant. Conclusion Routine UA with reflex UCx during post-transplant clinic visits accounted for the majority of cases of ASB within the first 3 months post-transplant. Decreasing the ordering of UA-guided reflexive UCx has the potential to reduce the identification of ASB and associated costs. Disclosures Ajit P. Limaye, MD, GSK: Advisor/Consultant|Memo: Advisor/Consultant|merck: Advisor/Consultant|merck: Grant/Research Support|Moderna: Advisor/Consultant|NobelPharma: DSMB member|Novartis: DSMB member|syneos: DSMB member

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