Adult Transplant Recipients Research Articles

Viral epitope profiling of hematopoietic cell transplant recipients with respiratory syncytial virus upper respiratory tract and lower respiratory tract infections

Abstract Background The pre-fusion conformation of the F glycoprotein of respiratory syncytial virus (RSVpreF) has been the target of recent respiratory syncytial virus (RSV) therapies, including monoclonal antibodies for immunocompetent children and vaccines for the elderly. However, the utility of targeted therapies against RSVpreF is unknown in pediatric or adult hematopoietic cell transplant (HCT) recipients, and there are limited natural history studies characterizing humoral immune responses after RSV infection in HCT recipients. We utilized VirScan, a novel high-throughput profiling of antiviral antibody epitopes, to identify differences in global RSV-related epitope hits after an RSV infection. Methods We evaluated adult and pediatric allogeneic HCT recipients who acquired RSV from 12/2011 to 12/2019. Patients were categorized into 3 groups: upper respiratory tract infections (URTI) only, those who progressed from URTI to lower respiratory tract infections (progressors) and lower respiratory tract infections (LRTI) at diagnosis, and tested at baseline prior to infection (pre-RSV), at RSV URTI or LRTI diagnosis (RSV diagnosis), at LRTI progression (LRTI), 4-6 weeks after infection (Response 1) and >8 weeks after infection (Response 2), depending on sample availability. We interrogated the viral antibody repertoire using a serosurvey (VirScan) that detects immunoglobulin G responses to 206 viruses. VirScan metrics evaluated included: (1) number of RSV epitope hits, (2) log10 of the maximum RSV epitope binding signal (EBS), analogous to an antibody titer for each epitope, and (3) geometric mean of all RSV EBS. Kruskal-Wallis tests were used to compare groups for each VirScan metric at the different time points. Results A total of 129 samples from 39 patients were analyzed; 24 with URTI only, 8 progressors, and 7 with LRTI at diagnosis. At each time point, VirScan metrics were similar among the 3 patient groups (Table 1). Though patterns of VirScan metrics following RSV diagnosis varied by patient, most showed a modest increase in values (Figure 1). Conclusion In this preliminary study, we utilized the power of VirScan, a comprehensive serologic profiling tool of the entire human virome, to characterize RSV specific antibody changes after RSV infection in allogeneic HCT recipients. There were no differences in global RSV VirScan metrics between the 3 groups, suggesting that antibodies may not be the primary driver of viral infection attenuation in this population. Future analyses will focus on differences in individual epitope acquisition, including RSVpreF, between the 3 groups, and investigate possible interactions with humoral responses to other viruses. Figure 1. Longitudinal RSV VirScan metrics for each patient separated by 3 groups (top row: RSV URTI only; middle row: progressors from URTI to LRTI; bottom row: LRTI at diagnosis). Each line is an individual patient. The different panels show the changes in RSV related epitope hits (A), the log10 maximum epitope binding signal (EBS) among RSV epitopes (B), and the geometric mean of all the RSV related EBS (C). Open circles represent time points prior to RSV diagnosis, filled circles represent time points just prior to, on or after URTI, and asterisks represent time points just prior to, on, or after LRTI.

Renal transplantation in older adults: retrospective cohort study to examine the impact of the new 2019 kidney offering scheme on older adult transplant recipients.

In 2019, a new kidney offering scheme was launched in the United Kingdom, aiming to better match estimated patient survival and graft life expectancy. The scheme's impact on older patients undergoing kidney transplantation (KT) is unknown. This study aims to compare the outcomes of older adult KT recipients before and after introduction of the 2019 scheme. A retrospective observational cohort study of older adults who underwent KT was undertaken. Group 1 were transplanted between 1 September 2017 and 31 August 2019 (2006 allocation scheme) and group 2 between 1 September 2019 and 31 August 2021 (2019 offering scheme). An older adult was any person ≥60 years old at the time of KT. Univariable binary logistic regression analysis was performed to determine odds ratios (OR) and 95% confidence intervals (CI). There were 107 older adult deceased donor KT recipients, 62 from group 1 and 45 from group 2. Median age at transplantation was 68 (interquartile range [IQR] 62-71) and 67 (IQR 64-73) years, respectively. Univariable analysis showed that re-intervention (OR 6.486, 95% CI 1.306-32.216, p = 0.022) and critical care admission (OR 5.619, 95% CI 1.448-21.812, p = 0.013) were significantly more likely in group 2. Group 2 recipients were significantly more likely to have a level 4 human leucocyte antigen (HLA) mismatch (OR 4.667, 95% CI 1.640-13.275, p = 0.004) and to have undergone previous KT (OR 4.691, 95% CI 1.385-15.893, p = 0.013). The introduction of the 2019 offering scheme was associated with re-intervention and critical care admission for older KT recipients. We also observed less-favourable HLA matches but more KT in difficult-to-match groups.

FSGS in an Adult Transplant Recipient Possibly Linked to a New Antibody against WT1

FSGS in an Adult Transplant Recipient Possibly Linked to a New Antibody against WT1

Torque Teno Virus Loads as a Marker of Immunosuppression in Pediatric Kidney Transplant Recipients.

Long-term renal function and survival after kidney transplantation rely on appropriate immunosuppressive treatment to prevent the risk of rejection. New biomarkers are needed to accurately assess the degree of immunosuppression in renal transplant recipients in order to avoid organ rejection and the development of opportunistic infections. Highly prevalent in humans, torque teno virus (TTV), which belongs to the family Anelloviridae, is a small, nonenveloped, single-stranded DNA virus which has not been linked with any specific human illness, but which constitutes a major component of the human virome. Host antiviral responses allow TTV levels to be controlled; however, viral persistence remains, explaining the high prevalence in human populations, including healthy individuals. Important confounders of TTV load include time since transplantation, age, gender, obesity, and smoking status. TTV-based guidance of immunosuppressive drug dosing could help with risk stratification, reducing the risk of infection, graft rejection and oncologic disease on an individual level, enabling long-term patient and graft survival. Original studies were accessed by a systematic search from electronic databases including PubMed, ScienceDirect and Wiley Online Library. The presented data mainly derive from adult transplant recipients showing an association between TTV plasma levels and the immune status of the host: High-TTV load and high immunosuppression are associated with a risk of infection, and low-TTV load and low immunosuppression indicate a risk of rejection. However, there is minimal information on pediatric transplant recipients with further research required in this cohort. To date, it has been demonstrated that longer posttransplant times are significantly associated with lower TTV levels in children with renal transplant. Meanwhile, an association between lower TTV loads and increased risk of graft reject during the first year of transplantation was also reported. More recently, Eibensteiner etal. revealed a robust, independent association between TTV plasma load and the onset of Cytomegalovirus and BK virus infections. Data from randomized controlled trials are still missing, even in adults, but a multicenter randomized controlled trial for TTV-guided immunosuppression in adult kidney recipients (TTVguideIT) began in 2022. There is, therefore, great promise for TTV levels to be used as a biomarker that could potentially improve both graft and patient survival in transplantation.

Examining intra-host genetic variation of RSV by short read high-throughput sequencing.

Every viral infection entails an evolving population of viral genomes. High-throughput sequencing technologies can be used to characterize such populations, but to date there are few published examples of such work. In addition, mixed sequencing data are sometimes used to infer properties of infecting genomes without discriminating between genome-derived reads and reads from the much more abundant, in the case of a typical active viral infection, transcripts. Here we apply capture probe-based short read high-throughput sequencing to nasal wash samples taken from a previously described group of adult hematopoietic cell transplant (HCT) recipients naturally infected with respiratory syncytial virus (RSV). We separately analyzed reads from genomes and transcripts for the levels and distribution of genetic variation by calculating per position Shannon entropies. Our analysis reveals a low level of genetic variation within the RSV infections analyzed here, but with interesting differences between genomes and transcripts in 1) average per sample Shannon entropies; 2) the genomic distribution of variation 'hotspots'; and 3) the genomic distribution of hotspots encoding alternative amino acids. In all, our results suggest the importance of separately analyzing reads from genomes and transcripts when interpreting high-throughput sequencing data for insight into intra-host viral genome replication, expression, and evolution.

Hepatitis B Vaccine Compliance, Serologic Response, and Durability in Adult Thoracic Organ Transplant Recipients

ABSTRACTIntroductionHepatitis B virus (HBV) vaccination is recommended for solid organ transplant (SOT) candidates. However, there is a lack of data on the HBV vaccine compliance, serologic response, and durability of HBV seroprotection in thoracic organ transplantation recipients.MethodsWe conducted a retrospective study of adult thoracic organ (heart and lung) transplant candidates who received HBV vaccination at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Conventional recombinant hepatitis B vaccine (Recombivax HB) was used before 2020, and Heplisav‐B was preferred after 2020. HBV seroprotection was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L. Furthermore, we compared characteristics between recipients who maintained HBV seroprotection and those who lost HBV seroprotection (HBsAb < 10 IU/L) at 30 days posttransplantation (D30).ResultsAmong 922 candidates who were eligible for HBV vaccination, 430 (47%) completed the HBV vaccine series. Patients receiving Heplisav‐B were more likely to complete the series than Recombivax HB (81% vs. 60%, p < 0.001) and Heplisav‐B had a higher seroprotection rate than Recombivax HB (75% vs. 64%, p = 0.023). Multivariate logistic regression analysis identified receiving Heplisav‐B as an independent predictor for HBV seroprotection (adjusted odds ratio [aOR] 1.723; 95% confidence interval [CI] 1.056–2.810; p = 0.029). A total of 145 thoracic organ transplant recipients achieved HBV seroprotection at the date of transplantation. Loss of HBV seroprotection occurred in 38 (26%) patients at D30. Multivariate logistic regression analysis identified two predictors for HBV seroprotection loss at D30: age ≥ 60 years (aOR, 2.503; 95% CI 1.026–6.107; p = 0.044), and pretransplant HBsAb level between 10 and 100 IU/L (aOR, 18.575; 95% CI 5.211–66.209; p < 0.001).ConclusionsAlthough less than half of thoracic organ transplant candidates completed HBV vaccine series pretransplant, Heplisav‐B provided a higher vaccine completion rate and seroprotection than the 3‐dose Recombivax HB. Clinicians should also be aware of the increased loss of HBV seroprotection in thoracic organ transplant recipients with age ≥ 60 years and pretransplant HBsAb between 10 and 100 IU/L. Assessment of seroprotection after HBV vaccination should be prioritized during the pretransplant period.

Liver and pancreas transplantation in adult donor and recipients with situs inversus totalis: a case series and review of the literature

BackgroundSitus inversus totalis is a rare congenital anomaly characterized by a mirror-image orientation of abdominal, and in some cases, thoracic organs. Here, we report our situs inversus totalis transplantation experience and further review liver transplantations in adult recipients and donors with situs inversus totalis.Case presentationWe describe three cases with situs inversus totalis. The first case was liver transplantation in a recipient (a 61-year-old Iranian man) with situs inversus totalis, the second was a liver transplantation from a donor (a 52-year-old Iranian woman) with situs inversus totalis, and finally, for the first time, a simultaneous pancreas and kidney transplantation in a recipient (a 26-year-old Iranian man) with situs inversus totalis. In patient one, hepatectomy could be performed according to the standard method and on the basis of preoperative studies. Hepatic vein and arterial anastomosis were performed as in every other patient without situs inversus totalis. To prevent biliary complications, a Roux-en-Y hepaticojejunostomy was performed. In patient two, implantation time, suprahepatic vein, portal vein, arterial, and biliary reconstruction could be done as in any other case without situs inversus totalis. Plication of the right-sided diaphragm and fixation of the falciform ligament was done for our patient. In patient three, systemic drainage was preferred to portal flow for establishing the outflow drainage of the pancreas compared with otherwise normal patients.ConclusionAlthough situs inversus totalis is a rare condition, our reported techniques are suitable, considering advantages such as easier accessibility, more acceptable placement of the implanted organs regarding vascular variations, and the appropriate location of the allograft in the proximity of other organs.

The Adolescent Transplant Recipient: An Overview of Neurocognitive Functioning and Implications for Long-Term Outcomes.

Solid organ transplantation (SOT) offers improved long-term survival for youth with end-stage organ disease. From a neurodevelopmental, cognitive, and academic perspective, children with solid organ transplant have a number of unique risk factors. While cognitive functioning may improve post-transplantation, it is important to understand the trajectory of neurocognitive development starting in transplant candidacy to evaluate the implications of early deficits. The aim of this paper is to describe the neurocognitive risks and long-term implications for adolescent transplant recipients. This paper provides an overview of neurocognitive functioning in youth with end-stage organ dysfunction with discussion of implications for adolescent transplant recipients. Post-transplant, adolescent, and young adult solid organ transplant recipients exhibit significant levels of executive dysfunction, with implications for decision-making, regimen adherence, and transition to adult transplant care. Transplantation may reduce the risk for poor long-term neurocognitive effects, yet adolescent transplant recipients remain at increased risk, particularly in executive functioning, which has implications for adherence and transition to adulthood. Baseline and follow-up assessments for youth with end-stage organ disease and transplant are important for the monitoring of neurocognitive development and may be used to mitigate risk for low adherence to post-transplantation treatment regimens and reduce barriers to transitioning to adult transplant care.

LCP-Tacrolimus Extended-Release (Envarsus XR) Use in Adolescent and Young Adult Solid Organ Transplant Recipients.

Limited published experience describes once daily, extended-release tacrolimus (LCP-Tac) use in pediatric solid organ transplantation (SOT), particularly nonrenal SOT. LCP-Tac can simplify immunosuppression (IS) regimens, minimize immediate release-tacrolimus (IR-Tac)-associated adverse effects, and promote adherence. This study describes the successful use of LCP-Tac in adolescent and young adult (AYA) SOT populations. A single-center, retrospective chart review of AYA SOT recipients (age < 25 years) converted from IR-Tac to LCP-Tac. Graft survival, biopsy-proven acute rejection (BPAR), infection rates, estimated glomerular filtration rate (eGFR), and pill burden were assessed at five time points postconversion (1, 3, 6, 12, and 24 months). Intrapatient variability of tacrolimus, as assessed by coefficient of variability (CV%), was also analyzed. Twenty-nine AYA SOT recipients (19 heart, 6 kidney, and 4 liver) were converted to LCP-Tac, with a median age of 17.4 years at conversion. Conversion, mainly due to perceived or identified medication nonadherence, occurred at a median of 5.4 years posttransplant. No graft loss occurred within 24 months of conversion, and BPAR incidence rate was consistent with previous reports for these populations. Only one patient experienced CMV infection. Renal function remained stable postconversion. Successful conversion from IR-Tac to LCP-Tac was demonstrated in AYA heart, kidney, and liver transplant recipients. These AYA SOT recipients experienced reduced pill burden and improved tacrolimus trough concentration variability. However, the impact on medication adherence warrants further investigation. Future research should explore the targeted use of LCP-Tac to enhance IS tolerability and medication adherence in young SOT populations.

Refractory/Resistant Cytomegalovirus Infection in Transplant Recipients: An Update.

Despite the significant progress made, CMV infection is one of the most frequent infectious complications in transplant recipients. CMV infections that become refractory or resistant (R/R) to the available antiviral drugs constitute a clinical challenge and are associated with increased morbidity and mortality. Novel anti-CMV therapies have been recently developed and introduced in clinical practice, which may improve the treatment of these infections. In this review, we summarize the treatment options for R/R CMV infections in adult hematopoietic cell transplant and solid organ transplant recipients, with a special focus on newly available antiviral agents with anti-CMV activity, including maribavir and letermovir.

Single-center experience of intraoperative ligation of the splenic artery for prevention of splenic artery steal syndrome in patients after living donor liver transplant

Background. Living donor liver transplant is an effective method of treatment in patients with different types of endstage liver diseases. Unfortunately, patients undergoing such a complex treatment sometimes develop various vascular complications. Splenic artery steal syndrome has emerged as a cause of graft ischemia in living donor liver transplant recipients and may lead to high liver enzyme levels, cholestasis, hepatic artery thrombosis, and even a graft loss in some severe cases.Objective. Evaluation of the first results in the experience of our center with a routine intraoperative ligation of the splenic artery during the procedure of right lobe living donor liver transplantation in adult recipients for the prevention of the steal syndrome development in the postoperative period.Material and methods. Living donor liver transplant recipients with known hepatic arterial flow impairment were retrospectively studied. Patients were allocated into groups with regard whether the splenic artery had been ligated or not during the transplant procedure. Arterial complications were reviewed in both groups.Results. None of 30 patients with ligated splenic artery developed splenic artery steal syndrome after living donor liver transplant. splenic artery steal syndrome occurred in 60% patients with non-ligated splenic artery. Surgical technique of performing arterial anastomosis was not related to the splenic artery steal syndrome development (p&lt;0.01 There was no local ischemic necrosis noted in the spleen in patients with the ligated splenic artery.Conclusion. Based on the analysis of our own experience and literature data, the splenic artery ligation appears to be an effective and safe method for preventing a splenic artery steal syndrome in patients following right lobe liver transplantation, with a minimal risk of ischemic complications for the spleen. However, further studies with larger sample sizes are needed to obtain more reliable results. Ultrasound examination and endovascular intervention are the primary tools for an early detection of abnormalities and rapid restoration of arterial blood flow in the hepatic artery of the graft.

Efficacy and Safety of Remdesivir in Adult Solid Organ Transplant Recipients: A Scoping Review.

The SARS-CoV-2 infection has been associated with important mortality, particularly in immunocompromised patients, including solid organ transplant (SOT) recipients. Remdesivir (RDV) is an antiviral drug that has proven to be effective in reducing the replication of the virus in host cells, by which it may reduce the progression of symptoms and, consequently, the length of hospital stay and mortality. Randomized controlled trials have evaluated its use in the general population but never in SOT recipients. For the first time in this review, the safety and efficacy of RDV is evaluated in this specific population. The literature research was conducted using PubMed/MEDLINE and Scopus databases from 1 January 2020 to 24 November 2023, and 23 studies were analyzed. Although no clinical studies specifically evaluating this population have been conducted yet, RDV is likely safe for SOT patients when compared to the general population, so prescribers should consider utilizing RDV in SOT patients who are at high risk for progression to severe COVID-19. Future research will allow for the confirmation of the observed results and the acquisition of broader and clearer data regarding the safety and efficacy of the drug in this specific setting.

Cellular and humoral immunogenicity against SARS-CoV-2 vaccination or infection is associated with the memory phenotype of T- and B-lymphocytes in adult allogeneic hematopoietic cell transplant recipients

We conducted a cross-sectional study to evaluate cellular and humoral immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or infection and examine how lymphocyte subpopulations in peripheral blood correlate with cellular and humoral immunogenicity in adult allogeneic hematopoietic cell transplantation (HCT) recipients. The median period from SARS-CoV-2 vaccination or infection to sample collection was 110.5 days (range, 6–345 days). The median SARS-CoV-2 spike-specific antibody level was 1761 binding antibody units (BAU)/ml (range, 0 to > 11,360 BAU/ml). Enzyme-linked immunosorbent spot (ELISpot) assay of T cells stimulated with SARS-CoV-2 spike antigens showed that interferon-gamma (IFN-γ)-, interleukin-2 (IL-2)-, and IFN-γ + IL-2-producing T cells were present in 68.9%, 62.0%, and 56.8% of patients, respectively. The antibody level was significantly correlated with frequency of IL-2-producing T cells (P = 0.001) and IFN-γ + IL-2-producing T cells (P = 0.006) but not IFN-γ-producing T cells (P = 0.970). Absolute counts of CD8+ and CD4+ central memory T cells were higher in both IL-2- and IFN-γ + IL-2-producing cellular responders compared with non-responders. These data suggest that cellular and humoral immunogenicity against SARS-CoV-2 vaccination or infection is associated with the memory phenotype of T cells and B cells in adult allogeneic HCT recipients.

T cell-mediated rejection and cancer risk in 579,905 organ transplant recipients.

10552 Background: Prolonged immunosuppression following organ transplant raises post-transplant malignancy (PTM) risk without affecting chronic rejection graft failure (CRGF) rates. Our study investigated if T cell responses during rejection could protect against cancer, whereas T cell suppression in PTM might prevent rejection. Methods: Data from 1987 to 2023 on adult first-time single-organ transplant recipients were collected from the UNOS-OPTN database, excluding those with a history of malignancy. Time-dependent Cox regression and landmark analyses (at 1, 2, 3, 5, 10, 15, and 20 years) were used to explore the link between rejection-induced graft failure (RGF) and PTM. Results: The study included 579,905 recipients (kidney 386,878, liver 108,390, heart 45,046, lung 37,643, pancreas 1,948), with a mean follow-up of 7.3 years. RGF occurred in 9.5% of recipients (kidney 12.1%, liver 1.8%, heart 3.9%, lung 12.0%, pancreas 10.2%; p&lt;0.001), with 2.1% experiencing acute rejection graft failure (ARGF) and 7.4%, CRGF. PTM occurred in 12.0% of recipients (kidney 9.9%, liver 12.4%. heart 20.9%, lung 22.6%, pancreas 11.3%; p&lt;0.001), including breast (0.5%), digestive (1.2%), genitourinary (1.7%), gynecologic (0.1%), head and neck (0.3%), hematologic (1.4%), musculoskeletal (0.1%), neurologic (0.0%), respiratory (1.1%), and skin/Kaposi sarcoma (6.4%). In recipients with RGF, PTM risk significantly decreased (HR 0.21 [0.19-0.24]; p&lt;0.001), with consistent trends observed across seven time landmarks (HR 0.20-0.07; p&lt;0.001). Both ARGF and CRGF were associated with lower PTM risk (HR 0.23 [0.18-0.29], 0.21 [0.19-0.24]; p&lt;0.001). In organ-specific analyses, kidney transplants showed similar outcomes for RGF, ARGF, and CRGF (HR 0.21-0.22; p&lt;0.001). Lung transplants exhibited significant risk reductions with RGF (HR 0.44 [0.22-0.89]; p=0.02) and CRGF (HR 0.47 [0.24-0.94]; p=0.03), with no significant results in other organs. All findings remained consistent even after excluding re-transplantations and deaths due to rejection. Excluding PTM-related deaths from PTM cases significantly lowered RGF risk (HR 0.69 [0.65-0.73]; p&lt;0.001), a trend that was consistent across all time landmarks (HR 0.51-0.80; p&lt;0.001). This inverse pattern was seen in kidney, liver, heart, and lung transplants (HR 0.90 [0.84-0.95], 0.21 [0.11-0.38], 0.21 [0.14-0.31], 0.18 [0.14-0.23]; p&lt;0.001) but not in pancreas transplants (HR 1.62 [0.69-3.77]; p=0.27). Conclusions: This study shows that rejection lowers cancer risk in kidney and lung transplants and that PTM reduces rejection risk in kidney, liver, heart, and lung transplants. Implementing enhanced cancer screening for those who have not experienced rejection may be considered. Further research is needed to elucidate the underlying T cell biology specific to each type of transplant.

#2986 Patiromer for hyperkalemia in the early post-transplant period

Abstract Background and Aims Hyperkalemia is a serious condition among kidney transplant (KT) recipients, which can lead to life-threatening complications such as cardiac arrhythmias. Following kidney transplantation, the causes of hyperkalemia are multifactorial owing to graft function, excess potassium repletion, comorbidities, and medications used in the peri- and post-operative setting. The risk for hyperkalemia is increased immediately post-transplantation, particularly in those with suboptimal graft function and higher calcineurin inhibitors levels. A rapidly rising potassium refractory to medical therapy can be an indication for dialysis. Managing hyperkalemia after kidney transplantation is associated with increased morbidity and healthcare costs. In that manner, newer alternatives such as patiromer and sodium zirconium cyclosilicate have emerged due to their potentially superior efficacy and safety profiles. Method This is an observational, retrospective, single-center study aimed to evaluate the efficacy and safety of patiromer for hyperkalemia management in adult transplant recipients over the first 3 months post-transplant period, between January and December 2022 (since patiromer is available in our hospital pharmacy). We included all the kidney transplant recipients of our hospital, with the exception of those with primary graft failure. Information concerning the donor, recipient, graft, drugs pre and post-transplant, fluid therapy, transfusions, and blood tests (ions, blood gases, glycemia, kidney function measurements, anticalcineurin inhibitors levels) were collected. Patiromer was administered in a single-daily dose, diluted in 250 cc of water, in the afternoon, at least 2 hours separated of other drugs. Results In total, 69 recipients were included in the analysis. 94% were from deceased donors and 54% from donation after cardiac death. The average age of the entire cohort was 55 years and 66% were male. Medical history of each KT recipients reveal that 89% has hypertension, 32% diabetes, and 35% previous cardiopathy. Hypertension treatment before the KT included beta-blockers (39%) and angiotensin-converting enzyme inhibitors (37%). The incidence of hyperkalemia (K ≥ 5.5 mmol/L) was 29.7% in the first three months, mostly in the first week (21.6%). Patiromer was administered to 37% of them. For the 88.5% an initial dose of 8.4 g/day was enough. Although, 27% required an increase of the dose to 16.8 g/day and 8% to 25.2 g/day. The changes in serum potassium levels following the first patiromer dose are shown in Graphic 1. The mean time duration of the patiromer treatment was 14.5 days (3.7-36.7). However, 27% continue with patiromer beyond three months. There was no significant difference in the dose/levels of tacrolimus neither in the serum magnesium levels between patients with or without patiromer. No gastrointestinal complications were observed following the use of patiromer. Conclusion Patiromer may play an important role in the management of hyperkalemia over the first weeks after KT, allowing a significant and sustained reduction of the serum potassium levels, although additional long-term studies are necessary to confirm these effects.

#2300 Validation study of the 4-variable kidney failure risk equation for prediction of allograft loss in a group of pediatric kidney transplant recipients

Abstract Background and Aims Emerging evidence suggests that the 4-variable Kidney Failure Risk Equation (KFRE) can be used to predict the risk of graft failure in adult transplant recipients. However, research studies in pediatric patients are lacking. This study aimed to validate the 4-variable KFRE (age, sex, estimated glomerular filtration rate [eGFR], and urine albumin-to-creatinine ratio [uACR]) for prediction of the 2- and 5-year risk of graft failure in a group of pediatric transplant patients. Method A retrospective observational study involving 59 pediatric patients who underwent kidney transplant between January 2007 and December 2017 was conducted. The KFRE risk scores were calculated with data collected at 1-year post-transplantation. The area under the receiver operating characteristic curves (AUC) and calibration plots were used to assess the discrimination and calibration properties of the 4-variable KFRE in predicting the risk of graft failure at 2 and 5 years from the point of the 1-year post-transplantation measurements. Results Among the 59 patients, 41 (69.5%) were male, with median age of 12.8 years (interquartile range 9.2-15.7) at the time of the kidney transplant. Eleven (18.6%) were living donor recipients. Median eFGR at 1-year post-transplantation was 62.0 mL/min/1.73 m2 (50.0-76.5); 1 (1.7%) and 3 (5.1%) patients developed graft failure within 2 and 5 years from the point of the 1-year post-transplantation measurements, respectively. The 4-variable KFRE showed excellent discrimination for the 2-year risk (AUC 0.966, 95% confidence interval [CI] 0.914-1.000) and very good discrimination for the 5-year risk (AUC 0.887, 95% CI 0.732-1.000). Calibration plots however showed imprecise calibration. A discernible trend was apparent in this sample, suggesting that living donor recipients have increased probability of experiencing graft failure in the first 5 years (p = 0.069). Conclusion The 4-variable KFRE may be of interest in predicting kidney failure progression in pediatric kidney transplant recipients using data at 1-year post-transplant, however to substantiate these findings and ensure the robustness of conclusions, larger-scale studies should be conducted.

Evaluation of the Tasso+ blood self-collection device for quantitation of plasma cytomegalovirus (CMV) DNAemia in adult solid organ transplant recipients (SOTr).

We evaluate an FDA-cleared blood self-collection device (Tasso+) and demonstrate that it is patient-acceptable and yields a liquid blood sample with quantitative CMV DNAemia results comparable to those of standard venipuncture samples. This opens up possibilities for self-blood collection to monitor for CMV and potentially other viruses in transplant and other at-risk populations.

Long-term Safety in Epstein-Barr Virus-Seropositive Kidney-only Transplant Recipients Treated With Belatacept in Clinical Practice: Final Study Results From the ENLiST Registry.

Belatacept, a selective T-cell costimulation blocker, was associated with improved survival and renal function but also with a risk of posttransplant lymphoproliferative disorder (PTLD) in adult kidney transplant recipients in phase 3 trials. This registry examined long-term safety in Epstein-Barr virus (EBV)-seropositive kidney transplant recipients treated with belatacept. This US-based, prospective, voluntary, multicenter registry (Evaluating Nulojix Long-Term Safety in Transplant [ENLiST]) included adult EBV-seropositive kidney-only transplant recipients treated de novo (within 14 d of transplantation) with belatacept. Primary objectives were to estimate incidence rates of confirmed PTLD, central nervous system (CNS) PTLD, and progressive multifocal encephalopathy (PML). The minimum follow-up was 2 y. Of 985 enrolled transplant recipients, 933 EBV-seropositive patients received belatacept, with 523 (56.1%) receiving concomitant tacrolimus at transplant (for up to 12 mo). By study end, 3 cases of non-CNS PTLD (incidence rate, 0.08/100 person-years), 1 case of CNS PTLD (0.03/100 person-years), and no cases of PML had been reported. Two patients with non-CNS PTLD received concomitant belatacept and tacrolimus and 1 received belatacept and lymphocyte-depleting therapy. Incidence rates were comparable between patients who received concomitant belatacept and tacrolimus and those who did not receive tacrolimus (0.09/100 person-years and 0.07/100 person-years, respectively; P = 0.96). Two of 4 patients with PTLD died, and 2 were alive at the end of the study. Cumulatively, 131 graft losses or deaths were reported by study end. Our results from the ENLiST registry, a large, prospective real-world study, showed that the incidence rates of PTLD and CNS PTLD in belatacept-treated EBV-seropositive transplant recipients were consistent with findings from previous phase 3 trials.

Comparison of intermittent intravenous tacrolimus to continuous tacrolimus in adult allogeneic stem cell transplant recipients.

Introduction: Initial continuous intravenous (CIV) tacrolimus (0.03 mg/kg/day based on ideal body weight [IBW]) has been favored for graft versus host disease (GVHD) prevention in allogeneic stem cell transplant patients due to the consistent, steady-state degree of immunosuppression; however, this method poses many logistical challenges. We implemented intermittent (IIV) tacrolimus at a starting dose of 0.015 mg/kg IBW twice daily over 4 h. To our knowledge this is the first retrospective comparison of CIV to IIV tacrolimus. Objectives: The primary objective was to evaluate the safety of IIV tacrolimus in comparison to CIV with respect to nephrotoxicity and neurotoxicity. The secondary objectives were to compare the incidence of grade II-IV acute GVHD (aGVHD) and chronic GVHD (cGVHD) at day +180, outcomes including relapse and overall survival, cell engraftment, and reactivation of cytomegalovirus and Epstein-Barr virus. Methods: This retrospective, single-center review evaluated adults who received an allogeneic stem cell transplant patients between January 1, 2020, and December 31, 2022. Results: Fifty-one unique patients were eligible for evaluation - 28 in the IIV cohort and 23 in the CIV group. The number of patients who developed nephrotoxicity and neurotoxicity were comparable between groups with no significant differences noted. No severe neurotoxicity was identified in either population. Secondary objectives revealed no significant difference in GVHD incidence or survival outcomes. Conclusion: IIV tacrolimus is comparable to CIV in terms of safety while also maintaining similar outcomes at day +180. IIV is a safe and feasible alternative to CIV in adult allogeneic stem cell transplant recipients.

The use of once-daily LCP-Tacrolimus with adolescent and young adult solid organ transplant recipients.

Adolescent and young adult (AYA) solid organ transplant (SOT) recipients experience increased rates of rejection and graft loss surrounding the time of health care transition, in part due to poor medication adherence. This study aims to examine the impact of a once-daily formulation of tacrolimus, LCP-tacrolimus (LCPT), on medication adherence for AYA SOT patients. A retrospective descriptive analysis was performed for all patients who underwent SOT and were prescribed LCPT after the age of 12 at our single-center pediatric hospital. Medication adherence was assessed via provider documentation and the medication level variability index (MLVI). Twenty-nine patients were prescribed LCPT as part of their immunosuppression regimen. Twenty patients were converted to LCPT from immediate-acting (IR) tacrolimus; six patients were initiated immediately following transplant, and three patients were unable to receive LCPT due to insurance denial. There was a numeric improvement in medication adherence for converted patients when measured by provider assessment (45.0% vs. 68.4%, p = .140) and MLVI (40.0% vs. 71.4%, p = .276), though these did not reach statistical significance. There were no differences in episodes of rejection or adverse effects. LCPT prescription was not associated with decreased medication burden, and two patients transitioned back to IR tacrolimus due to increased cost. LCPT use did not significantly improve patient adherence; however, it resulted in numerically higher perceived and measured adherence rates. LCPT appears to be safe and effective in the management of SOT recipients; however, it may not affect pill burden and may result in a higher financial burden. Use may be considered for a select group of AYA SOT recipients.