Post-transplant Patients Research Articles

Safety but limited efficacy of donor lymphocyte infusion for post-transplantation cyclophosphamide-treated patients

The therapeutic efficacy of donor lymphocyte infusions (DLIs) given after allogeneic hematopoietic cell transplantation (HCT) is limited by risk of graft-versus-host disease (GVHD). Post-transplantation cyclophosphamide (PTCy) effectively prevents severe GVHD, but there are limited data on outcomes of DLIs given to PTCy-treated patients. We reviewed 162 consecutive PTCy-treated patients transplanted between 2015–2022 within the Center for Immuno-Oncology at the National Cancer Institute. Of 38 DLIs given to 21 patients after 22 HCTs, few DLIs were associated with toxicities of acute GVHD (7.8%), cytokine release syndrome (CRS, 7.8%), or chronic GVHD (2.6%), and all occurred in those receiving serotherapy-containing pre-HCT conditioning (50% of HCTs). Seven DLIs resulted in complete response (18.4%), with 5 of these given after HCTs using serotherapy-containing conditioning. Excluding infectious indications, complete response to DLIs given after transplants with versus without serotherapy-containing pre-HCT conditioning were 30% and 4.3%, respectively. Two patients received DLI for infection and experienced complete resolution without GVHD or CRS, although the efficacy cannot be definitively attributable to the DLI. DLIs given to PTCy-treated patients had low toxicity but limited efficacy, although pre-HCT serotherapy may modulate both toxicity and response. Novel strategies are needed to enhance the therapeutic efficacy of post-transplant cellular therapies without aggravating GVHD.

Kidney transplantation in children and adolescents with C3 glomerulopathy or immune complex membranoproliferative glomerulonephritis: a real-world study within the CERTAIN research network

BackgroundComplement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are ultra-rare chronic kidney diseases with an overall poor prognosis, with approximately 40–50% of patients progressing to kidney failure within 10 years of diagnosis. C3G is characterized by a high rate of disease recurrence in the transplanted kidney. However, there is a lack of published data on clinical outcomes in the pediatric population following transplantation.MethodsIn this multicenter longitudinal cohort study of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, we compared the post-transplant outcomes of pediatric patients with C3G (n = 17) or IC-MPGN (n = 3) with a matched case–control group (n = 20).ResultsEleven of 20 children (55%) with C3G or IC-MPGN experienced a recurrence within 5 years post-transplant. Patients with C3G or IC-MPGN had a 5-year graft survival of 61.4%, which was significantly (P = 0.029) lower than the 5-year graft survival of 90% in controls; five patients with C3G or IC-MPGN lost their graft due to recurrence during this observation period. Both the 1-year (20%) and the 5-year (42%) rates of biopsy-proven acute rejection episodes were comparable between patients and controls. Complement-targeted therapy with eculizumab, either as prophylaxis or treatment, did not appear to be effective.ConclusionsThese data in pediatric patients with C3G or IC-MPGN show a high risk of post-transplant disease recurrence (55%) and a significantly lower 5-year graft survival compared to matched controls with other primary kidney diseases. These data underscore the need for post-transplant patients for effective and specific therapies that target the underlying disease mechanism.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Clinical features and prognostic model for viral encephalitis after allogeneic haematopoietic stem cell transplantation.

The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients.

Usefulness of Picture Archiving and Communication System-Based Quantitative Ultrasound Measurements in Evaluation of Allograft Dysfunction in Patients With Liver Transplantation.

The aim of this study was to assess the usefulness of picture archiving and communication system (PACS)-based quantitative grayscale ultrasonography (US) measurements in detecting allograft dysfunction in posttransplant patients. In this retrospective study, 116 patients with liver transplantation who underwent biopsy for allograft evaluation were recruited from the database. All participants had US images prior to procedure. Normal, acute cellular rejection (ACR), recurrent hepatitis (Hep), or combined (ACR/Hep) groups were generated based on pathology results. Region of interests were drawn for liver and rectus abdominus muscle to perform quantitative US analysis. The liver/muscle mean ratio (L/M) and heterogeneity index (HI; liver standard deviation/liver mean) were obtained. The ratios of groups were compared, and receiver-operating-characteristic analysis was performed. There was a significant difference between normal (n = 16) and each of other groups (ACR, 39; Hep, 36; combined, 25) for L/M and HI (P < 0.05). No significant difference was detected between ACR, Hep, and combined groups. The areas under the curve for L/M and HI were 0.755 (moderate) and 0.817 (good), respectively. To differentiate abnormal (ACR, Hep, and combined) from normal allografts sensitivity, specificity, PPV, and NPV were 50.0%, 87.5%, 96.2%, and 21.9% for cut point of L/M ≥1 and 84.0%, 68.8%, 94.4%, and 40.7% for cut point of HI ≥0.2 with odds ratios of 7.52 (for L/M ≥1) and 13.10 (for HI ≥0.2), respectively (P < 0.01). L/M has moderate and HI has good discrimination of normal from abnormal allograft in liver transplant patients. PACS-based quantitative US measurements is an objective, easy to use, noninvasive auxiliary tool to discriminate hepatic allograft dysfunction.

Frailty after Liver Transplantation: A Complex Unexplored Issue.

Frailty is a multidimensional syndrome predominantly studied in the elderly, characterized by reduced resistance to stressors due to diminished physiological reserve and resilience. Advances in surgical techniques and immunosuppressive drugs have improved long-term survival rates in solid organ transplant recipients, yet the 10-year survival is satisfying. However, liver transplant recipients have a noteworthy risk of developing frailty status. After liver transplant, frailty can be favored by socioeconomic, cultural, and health-related factors, leading to increased risks of hospitalization, morbidity, and mortality. Various tools for frailty assessment exist, but none are universally validated for post-transplant patients. The integration of socioeconomic and psychological factors into frailty evaluation could improve quality of life and long-term outcomes for transplant recipients. Multidisciplinary approaches, including psychosocial support, are essential for managing frailty and enhancing the overall care of transplanted patients. This narrative review aims to comprehensively address the principal frailty risk factors associated with liver transplantation.

Effects and Safety of 5% Lifitegrast Ophthalmic Solution in Patients With Dry Eye Disease Associated With Ocular Graft-Versus-Host Disease.

Introduction Graft-versus-host disease (GVHD) is a common sequela of hematopoietic stem cell transplant (HSCT). While HSCT is often curative for certain hematologic malignancies, acute and chronic GVHD remains an important cause of morbidity and mortality in post-transplant patients. Ocular involvement is one manifestation of chronic GVHD that can present similarly to chronic dry eye with tear film abnormalities, aqueous deficiency, and corneal epithelial defects through melting and perforation. Current management includes frequent use of artificial tears and oral or topical glucocorticoids as tolerated. There is a need for long-term, steroid-sparing therapeutics in the management of ocular GVHD (oGVHD). Lifitegrast is approved for the treatment of chronic dry eye and may have therapeutic potential in the treatment of oGVHD. The aim of this study was to investigate the efficacy and safety of topical lifitegrast in the management of oGVHD. Methodology A prospective randomized clinical trial (NCT04792580) was performed on 32 enrolled patients with diagnosed oGVHD. Subjects underwent a two-week washout period consisting of preservative-free artificial tears dosed twice a day, after which they were randomized to the treatment arm (5% lifitegrast ophthalmic solution) or placebo arm (vehicle solution) for four weeks. Endpoints included Symptom Assessment iN Dry Eye (SANDE) score, unanesthetized Schirmer score, Ocular Surface Disease Index questionnaire score, fluorescein staining, tear film breakup time, meibum quantity, and turbidity. Safety endpoints included intraocular pressure, visual acuity, and rate of treatment-related adverse effects. Statistical analysis was done with a t-test or Wilcoxon rank-sum test. Results The primary and secondary efficacy endpoints were met, with statistically significant reductions in mean SANDEand unanesthetized Schirmer score observed at four weeks post-randomization. No serious adverse events related to the use of either lifitegrast or vehicle were observed, and no worsening of visual acuity or intraocular pressure occurred in the intention-to-treat analysis. However, further inference was limited due to insufficient statistical power owing to significant washout and a 50% dropout rate from the all-enrolled analysis set. The most common causes of study dropout were worsening of unrelated medical conditions (not GVHD) and improvement of SANDE score or Schirmer score outside of the inclusion criteria range during the washout period. Conclusions Lifitegrast may be a useful steroid-sparing agent in the long-term management of oGVHD. This study provides further support for the clinical evidence of lifitegrast in the management of dry eye signs and symptoms, although further sufficiently powered clinical trials are warranted to better understand its efficacy in the oGVHD population. Personalized treatment options targeting distinct manifestations of oGVHD in the cornea, tear film, lid margin, and conjunctiva are needed in the effective management of this multifaceted and complex disease.

Dynamic Relapse Prediction by Peripheral Blood WT1mRNA after Allogeneic Hematopoietic Cell Transplantation for Myeloid Neoplasms

Although various relapse prediction models based on pretransplant information have been reported, they cannot update the predictive probability considering post-transplant patient status. Therefore, these models are not appropriate for deciding on treatment adjustment and preemptive intervention during post-transplant follow-up. A dynamic prediction model can update the predictive probability by considering the information obtained during follow-up. This study aimed to develop and assess a dynamic relapse prediction model after allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) using peripheral blood Wilms' tumor 1 messenger RNA (WT1mRNA). We retrospectively analyzed patients with AML or MDS who underwent allo-HCT at our institution. To develop dynamic models, we employed the landmarking supermodel approach, using age, refined disease risk index, conditioning intensity, and number of transplantations as pretransplant covariates and both pre- and post-transplant peripheral blood WT1mRNA levels as time-dependent covariates. Finally, we compared the predictive performances of the conventional and dynamic models by area under the time-dependent receiver operating characteristic curves. A total of 238 allo-HCT cases were included in this study. The dynamic model that considered all pretransplant WT1mRNA levels and their kinetics showed superior predictive performance compared to models that considered only pretransplant covariates or factored in both pretransplant covariates and post-transplant WT1mRNA levels without their kinetics; their time-dependent areas under the curve were 0.89, 0.73, and 0.87, respectively. The predictive probability of relapse increased gradually from approximately 90 days before relapse. Furthermore, we developed a web application to make our model user-friendly. This model facilitates real-time, highly accurate, and personalized relapse prediction at any time point after allo-HCT. This will aid decision-making during post-transplant follow-up by offering objective relapse forecasts for physicians.

Exploring Pattern of Relapse in Pediatric Patients with Acute Lymphocytic Leukemia and Acute Myeloid Leukemia Undergoing Stem Cell Transplant Using Machine Learning Methods.

Background. Leukemic relapse remains the primary cause of treatment failure and death after allogeneic hematopoietic stem cell transplant. Changes in post-transplant donor chimerism have been identified as a predictor of relapse. A better predictive model of relapse incorporating donor chimerism has the potential to improve leukemia-free survival by allowing earlier initiation of post-transplant treatment on individual patients. We explored the use of machine learning, a suite of analytical methods focusing on pattern recognition, to improve post-transplant relapse prediction. Methods. Using a cohort of 63 pediatric patients with acute lymphocytic leukemia (ALL) and 46 patients with acute myeloid leukemia (AML) who underwent stem cell transplant at a single institution, we built predictive models of leukemic relapse with both pre-transplant and post-transplant patient variables (specifically lineage-specific chimerism) using the random forest classifier. Local Interpretable Model-Agnostic Explanations, an interpretable machine learning tool was used to confirm our random forest classification result. Results. Our analysis showed that a random forest model using these hyperparameter values achieved 85% accuracy, 85% sensitivity, 89% specificity for ALL, while for AML 81% accuracy, 75% sensitivity, and 100% specificity at predicting relapses within 24 months post-HSCT in cross validation. The Local Interpretable Model-Agnostic Explanations tool was able to confirm many variables that the random forest classifier identified as important for the relapse prediction. Conclusions. Machine learning methods can reveal the interaction of different risk factors of post-transplant leukemic relapse and robust predictions can be obtained even with a modest clinical dataset. The random forest classifier distinguished different important predictive factors between ALL and AML in our relapse models, consistent with previous knowledge, lending increased confidence to adopting machine learning prediction to clinical management.

Comparative Study between Cyclosporine Dynamics and Other Immunosuppressants in Patients Post Allogenic Stem Cell Transplantation

Abstract Background Bone marrow transplant has been successfully to treat diseases such as leukemia, lymphomas, aplastic anemia, immune deficiency disorders, and some solid tumor cancers. There is two types of bone marrow transplantation, one of two types of transplant may be carried out either an autograft, using the patient’s own bone marrow cells or an allograft (or allogeneic transplant), which allows the replacement of the diseased bone marrow with an healthy bone marrow taken from a compatible donor (related or unrelated) and to use the immune system of the healthy donor to fight the recipient’s illness. Aim of the Work To assess impact of cyclosporine introduction post-transplant on different organs and other immune suppressant as regards side effects and prophylactic efficacy against GVHD and good outcome of the transplantation. Patients and Methods The study enrolled two groups, 128 post-transplant patient their ages between 16 and 65, group 1 include 106 patients was taking cyclosporine for prophylaxis of GVHD, group 2 include 22 patients was taking other immunosuppressants mainly Tacrolimus and MMF. Results Incidence of GVHD occurrence was lower in group of cyclosporine as 30.2 % of them has no GVHD with statistically significant difference with P-value 0.007 and was lower in combined occurrence of acute and chronic GVHD,22.6 % in group 1 and 54.5 % of group 2 with P-value 0.006 Incidence of mild anemia was lower in group 1 with statistically significant difference with P-value 0.022 Hyponatremia was higher in group 1 (60.4 %) with statistically significant difference with P-value 0.026 AST levels elevated one fold higher in group 1 with statistically significant difference with P-value 0.009 and elevated three fold higher in group 2 with statistically significant difference with P-value &amp;lt; 0.001 ALT levels elevated one fold higher in group 1 with statistically significant difference with P-value 0.039 21 patients were presented with impairment of renal functions,12.5% with mild impairment, 3.9 % with moderate impairment, all of them from group 1 with statistically significant difference with P-value 0.023, more commonly in females and in age group from 16 to 45 years old. Conclusion Hematopoietic stem cell transplantation (HSCT) is a particularly important treatment for hematologic malignant and nonmalignant diseases. Unfortunately, following allogeneic HSCT, graft-versus-host disease, immunosuppression and susceptibility to opportunistic infections remain among the most substantial problems restricting the efficacy and use of this procedure. Cyclosporine remains the most effective prophylaxis post HSCT for prevention of GVHD, more multi centric studies are needed on wide scale to prove more relevant results that will be significant.

Chronological and Geographical Variations in the Incidence and Acceptance of COVID-19-Positive Donors and Outcomes Among Abdominal Transplant Patients.

Given the importance of understanding COVID-19-positive donor incidence and acceptance, we characterize chronological and geographic variations in COVID-19 incidence relative to COVID-19-positive donor acceptance. Data on deceased donors and recipients of liver and kidney transplants were obtained from the UNOS database between 2020 and 2023. Hierarchical cluster analysis was used to assess trends in COVID-19-positive donor incidence. Posttransplant graft and patient survival were assessed using Kaplan-Meier curves. From among 38429 deceased donors, 1517 were COVID-19 positive. Fewer kidneys (72.4%vs. 76.5%, p < 0.001) and livers (56.4%vs. 62.0%, p < 0.001) were used from COVID-19-positive donors versus COVID-19-negative donors. Areas characterized by steadily increased COVID-19 donor incidence exhibit the highest transplantation acceptance rates (92.33%), followed by intermediate (84.62%) and rapidly increased (80.00%) COVID-19 incidence areas (p = 0.016). Posttransplant graft and patient survival was comparable among recipients, irrespective of donor COVID-19 status. Regions experiencing heightened rates of COVID-19-positive donors are associated with decreased acceptance of liver and kidney transplantation. Similar graft and patient survival is noted among recipients, irrespective of donor COVID-19 status. These findings emphasize the need for adaptive practices and unified medical consensus in navigating a dynamic pandemic.

Reactive Chemical Gastropathy in PostLung Transplant Patient: A Rare Case Report

Abstract Reactive chemical gastropathy is also termed drug-induced gastropathy. The terms gastropathy and gastritis vary in their etiology ultimately causing mucosal injury. The gastric mucosa is different in different regions. The oxyntic mucosa is seen in the body and fundus while antral mucosa is seen in the antrum and pyloric region. Antral mucosa bares G-cell which gives fried egg appearance on hematoxylin and eosin stain. The normal gastric mucosa is devoid of neutrophils outside vascular spaces. Most of the drugs used in modern medicine are often associated with adverse effects, especially in the gastrointestinal tract, and are mild but can be life-threatening. Here, we discuss a case of a 67-year-old male who had undergone a lung transplant in 2023, followed by reactive chemical gastropathy in 2024 with deposition of Kayexalate crystals in gastric mucosa while being treated for hyperkalemia which is a rare entity noticed in posttransplant patients.

Assessing clinical benefits of live-attenuated vaccination in post-liver transplant patients: Analysis of breakthrough infections and natural boosters

Recently, live-attenuated measles, rubella, varicella, and mumps vaccines have been administered to carefully selected post-liver transplant patients. Although attention has been focused on post-vaccination antibody titers and adverse events, the real-life clinical benefits remain unclear. A comprehensive analysis of breakthrough infections and natural boosters (asymptomatic cases with significant elevation in virus antibody titers) following immunization post-liver transplantation was conducted from 2002-2023, exploring the timing, frequency, correlation with domestic outbreaks, and degree of antibody elevation. During the median 10-year observation period among 68 post-liver transplant patients, breakthrough infections occurred only in chickenpox, with 7 mild cases (1 episode/64 person-years). A total of 59 natural booster episodes (1, 5, 20, and 33 for measles, rubella, chickenpox, and mumps, respectively) were observed, with incidence rates of 1 per 569, 110, 22, and 17 person-years, respectively. The timing of natural boosters closely correlated with domestic outbreaks (P < .05 in chickenpox and mumps), influenced by local vaccine coverage. The degree of antibody elevation was significantly higher in individuals with breakthrough infections than in those with natural boosters (P < .05). These findings suggest that immunization with live-attenuated vaccines for post-liver transplant patients has demonstrated clinical benefits. Furthermore, mass vaccination has a positive impact on post-transplant patient outcomes.

Mycophenolate Dose Reduction in Tacrolimus-based Regimens and Long-term Kidney Transplant Outcomes in Australia and New Zealand.

Mycophenolate dose reduction (MDR) is associated with acute rejection and transplant failure in kidney transplant recipients (KTRs). The optimal dose to prevent rejection and reduce complications remains poorly defined in tacrolimus-based regimens. We assessed adult KTRs from 2005 to 2017 initiated on mycophenolate mofetil 2 g/d, tacrolimus, and prednisolone from the Australia and New Zealand Dialysis and Transplant Registry. KTRs with rejection within the first 30 d posttransplant were excluded. The primary outcome was time to first rejection between 30 d and 2 y posttransplant. Mycophenolate dose was modeled as a time-varying covariate using Cox proportional hazards regression. Secondary outcomes included assessment of early MDR to <1.5 g/d within the first 6 mo posttransplant and subsequent patient and death-censored graft survival. In the primary analysis, 3590 KTRs were included. Compared with mycophenolate dose of ≥2 g/d, both 1.0-<1.5 and <1 g/d were associated with an increased risk of rejection during the 2 y posttransplant (hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.29-2.16; P < 0.001 and HR 2.06; 95% CI, 1.36-3.13; P = 0.001, respectively) but not 1.5-<2 g/d (HR 1.20; 95% CI, 0.94-1.53; P = 0.14). Early MDR to <1.5 g/d occurred in 45.3% of KTRs and was an independent risk factor for death-censored graft failure (HR 1.32; 95% CI, 1.05-1.66; P = 0.016) but not death (HR 1.18; 95% CI, 0.97-1.44; P = 0.10), during a median follow-up of 5.0 (interquartile range, 2.6-8.5) y. Early MDR was a risk factor for subsequent rejection and graft failure in KTRs receiving contemporary tacrolimus-based regimens.

Long-term outcomes of active vaccination against de novo hepatitis B among pediatric recipients of living donor liver transplantations with anti-HBc (+) grafts: a retrospective case-control study.

Active vaccination has been utilized to prevent de novo hepatitis B virus infection (DNHB) in anti-HBc (+) grafts after liver transplantation (LT). However, the long-term efficacy of active vaccination and graft/patient outcomes of anti-HBc (+) grafts have yet to be comprehensively investigated. Among 204 pediatric patients enrolled in the study, 82 recipients received anti-HBc (+) grafts. For DNHB prevention, active vaccination was repeatedly administered prior to transplant. Anti-viral therapy was given to patients with pre-transplant anti-HBs<1000IU/ ml (non-robust response) for 2 years and discontinued when post-transplant patients achieved anti-HBs>1000IU/mL, while anti-viral therapy was not given in patients with an anti-HBs titer over 1000IU/mL. The primary outcome was to investigate the long-term efficacy of active vaccination, while the secondary outcomes included the graft and patient survival rates. Among the 82 anti-HBc (+) transplant patients, 68% of recipients achieved a robust immune response, thus not requiring antiviral therapy. Two patients (2.4%) developed DNHB infection, one of which was due to an escape mutant. With a median follow-up of 150 months, the overall 10-year patient and graft survival rates were significantly worse in recipients of anti-HBc (+) grafts than those of anti-HBc (-) grafts (85.2% vs 93.4%, P=0.026; 85.1% vs 93.4%, P=0.034, respectively). Additionally, the 10-year patient and graft outcomes of the anti-HBc (+) graft recipients were significantly worse than those of the anti-HBc (-) graft recipients after excluding early mortality and non-graft mortality values (90.8% vs 96.6%, P=0.036; 93.0% vs 98.3%, P=0.011, respectively). Our long-term follow-up study demonstrates that active vaccination is a simple, cost-effective strategy against DNHB infection in anti-HBc (+) graft patients, whereby the need for life-long antiviral therapy is removed. Notably, both the anti-HBc (+) grafts and patients exhibited inferior long-term survival rates, although the exact mechanisms remain unclear.

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

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

Mental Health and Substance Use Disorders in Transplant Waitlist, VAD, and Heart Transplant Patients: A TriNetX Database Analysis.

Background/Objectives: Mental health and substance use disorders (MHDs and SUDs) affect cardiac allograft and VAD recipients and impact their quality of life and compliance. Limited research currently exists on MHDs and SUDs in this population. Methods: This study compares the incidence of MHDs and SUDs in the transplant list, VAD, and post-transplant patients with that in heart failure patients. Study cohorts were derived from the TriNetX database using ICD-10 codes. Differences in incidence were examined using the log-rank test. Adults with MHDs and SUDs before the window of time were excluded. All comparisons were made between propensity-matched cohorts. Statistical significance was set at p < 0.05. Results: Transplant waitlist patients showed a significant increase in the incidence of anxiety, depression, panic, adjustment, mood, alcohol use, and eating disorders. Post-transplant patients showed a significant increase in depression and opioid use. VAD patients showed a significant increase in depression and a decrease in panic disorder and anxiety. These results allow for further investigations on prevention and coping strategies. Conclusions: The deterioration of mental health can significantly impact medication compliance, survival, and quality of life. Opioid use for pain management in the early postoperative period should be further investigated to assess its impact on long-term substance use and addiction.

Formulae for estimation of kidney function as an approach to calculating drug doses: A scoping review

Background: The kidneys are the main organ for drug excretion, and it is critical to assess kidney function when designing dosage regimens for drugs that undergo renal elimination. Various formulae have been used to estimate kidney function and safely adjust doses. Objective: This research reviewed studies that assessed patients' kidney function with various approaches to provide appropriate choices of kidney function estimation formulas based on patients' age and clinical conditions. Method: The search involved browsing scientific articles in PubMed and ScienceDirect with the keywords (("assessment") AND ("GFR") AND ("formula")) OR ("renal function") AND ("human")) AND (“Creatinine”). The articles included were those available in full text and English. Thirty articles addressing the formulae for kidney function assessment were reviewed. Result: The Schwartz formula is more appropriate for pediatric and adult patients, whereas the creatinine-based chronic kidney disease epidemiology (CKD-EPI) formula can be used in geriatrics, obese patients, and patients already known to have decreased kidney function. The cystatin C-based CKD-EPI formula is for patients with HIV and post-transplant patients. Conclusion: This study identified that physiological conditions, especially patients’ age and pathology, should be considered in devising formulae to estimate kidney function to accurately calculate safe drug doses.

A Decade-Long Cohort Analysis of Human Cytomegalovirus (HCMV)-Induced Early and Late Renal Rejection in Post-Transplant Patients in the Eastern Indian Population.

Background: HCMV causes severe clinical complications in transplant recipients and may lead to graft rejection. Successful renal transplantation heavily relies on the early prevention and diagnosis of CMV infections, followed by prompt prophylactic treatment before transplantation. Despite the majority of renal rejection cases with acute HCMV infections being asymptomatic and occurring one to two years later, the objective of this research was to comprehend the effect of late HCMV infection on renal rejection by examining specific clinical parameters in the Eastern Indian cohort. Method: In this study, 240 patients were studied for five years following transplantation, and their data were collected from the local metropolitan hospital in Eastern India. Both HCMV-positive and -negative post-transplant patients were investigated using the clinical parameters and viral loads for latent infection. Results: Within the studied population, 79 post-transplant patients were found to be HCMV positive. Among them, 13 (16.45%) patients suffered from renal rejection within less than 2 yrs. of transplantation (early rejection) and 22 (27.84%) patients suffered from renal rejection after 2 yrs. from the operation date (late rejection). Assessment of clinical parameters with respect to HCMV infection revealed that in early rejection cases, fever (p-0.035) and urinary tract infection (p-0.017) were prominent, but in late rejection, hematuria (p-0.032), diabetes (p-0.005), and creatinine level changes (p < 0.001) were significant along with urinary tract infection (p-0.047). Conclusions: This study provides valuable insights into monitoring latent CMV infections and highlights the understanding of reducing renal rejection rates and the need for further research in this field.

#1467 Pegcetacoplan for post-transplant recurrent C3 glomerulopathy or immune complex membranoproliferative glomerulonephritis in NOBLE: 12-week evolution

Abstract Background and Aims C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) are rare diseases caused by uncontrolled complement activation, resulting in excess deposition of C3 breakdown products in the kidneys, which leads to kidney damage and eventually kidney failure. Kidney transplantation is an option for end-stage kidney disease, but disease recurrence is common (up to 67% of patients), and up to 50% of transplant recipients lose renal allografts due to recurrence. Pegcetacoplan is a targeted C3 and C3b inhibitor that may prevent excess deposition of C3 and C5 breakdown products and subsequent glomerular inflammation and kidney damage in patients with C3G or IC-MPGN, potentially improving clinical outcomes. NOBLE (NCT04572854) was the first prospective randomized controlled trial of pegcetacoplan vs standard of care (SOC) in post-transplant patients with recurrent C3G or IC-MPGN. Method Adult patients were randomized 3:1 to subcutaneous pegcetacoplan 1080 mg twice weekly plus SOC (n = 10) or SOC only (n = 3) for 12 weeks followed by a 40-week non-controlled period in which all patients received pegcetacoplan. Primary and secondary endpoint results for Week-12 data have been reported. We conducted a patient-level post hoc analysis to describe key histology changes from renal biopsy (C3c staining, C3G histologic index activity score), clinical parameters (urine protein-to-creatinine ratio [uPCR; calculated from triplicate first-morning spot urine], estimated glomerular filtration rate [eGFR]), and biomarkers (serum C3, plasma sC5b-9) through Week 12. The C3G histologic index uses a semiquantitative scale of 0–3 for 7 markers of activity (mesangial hypercellularity, endocapillary proliferation, membranoproliferative morphology, leukocyte infiltration, cellular and/or microcellular crescent formation, fibrinoid necrosis, and interstitial inflammation), for a total activity score of 0–21. eGFR stability was defined as a decrease of no more than 25% versus baseline. Results Among the 10 pegcetacoplan-treated patients, 7 (70%) had 1 previous kidney transplant, 2 (20%) had 2, and 1 (10%) had 3. The mean (range) time to disease recurrence after most recent transplant was 10.8 (0.4–31.8) months and from most recent recurrence to randomization was 12.2 (2.1–37.7) months, with 60% randomized &amp;gt;6 months post-disease recurrence. Among the 3 SOC-only patients, 2 (66.7%) had 1 transplant and 1 (33.3%) had 2. Mean (range) time to recurrence was 32.8 (4.6–63.8) months and to randomization was 33.9 (7.0–65.4) months. At Week 12, 8 (80%) pegcetacoplan-treated patients had a reduction in C3c staining of at least 1 order of magnitude. Of these 8, 7 (70%) had a decrease in activity score, and 6 of these 7 (60%) had a decrease in proteinuria. Four (40%) patients had reduced C3c staining, decreased activity score, and cleared electron microscopy deposits at Week 12. eGFR remained stable in 9 (90%) patients. Six of 9 (67%) patients with available Week-12 data (4 of 5 patients with &amp;gt;1 g/g uPCR at baseline) had a reduction in uPCR with 5 of the 6 achieving ≥50% uPCR reduction (Table). All pegcetacoplan-treated patients had increased serum C3, as expected, and 9 (90%) had decreased sC5b-9. At Week 12, no TEAEs led to study discontinuation, treatment withdrawal, or death. No encapsulated bacterial infections or events of rejection/graft loss related to the study drug were reported. Conclusion As early as Week 12, more than half (6/10 [60%]) of post-transplant patients with recurrent C3G or IC-MPGN treated with pegcetacoplan achieved reductions in C3c staining, activity score of C3G histology index, and proteinuria, suggesting that pegcetacoplan targets the underlying pathophysiology of the C3G/IC-MPGN in kidney transplant recipients. The safety and efficacy of pegcetacoplan will be further evaluated at Week 52 of the NOBLE study and as part of the Phase 3 VALIANT (NCT05067127) trial, which enrolled patients with C3G or primary IC-MPGN who have native kidney or post-transplant disease.

#97 Study of association between post transplant diabetes mellitus (PTDM) and hypomagnesemia

Abstract Background and Aims New onset diabetes after transplantation (NODAT) or PTDM (Post-transplant Diabetes Mellitus) is associated with increased morbidity, renal graft loss, cardiovascular complications, mortality and increased health care costs. It has been shown that incidence of NODAT is rising in recent years. It is suggested that there is more prominent role of beta cell dysfunction rather than insulin resistance in patients with PTDM. Hypomagnesemia which is commonly seen in post-transplant patients is suggested to have a role in promoting beta cell dysfunction. Emerging modifiable risk factors for PTDM like hypomagnesemia need to be studied which may help to improve its prevalence and outcomes. Method This study was single centre study to assess association of PTDM or NODAT with hypomagnesemia. Other risk factors like body mass index (BMI) &amp;gt;25 kg/m2, higher age and sex of the recipient were also studied. This study was a prospective, non-randomised, comparative, observational study. Duration of the study was from 1st October 2016 to 28th February 2018. Recipients with age &amp;gt; 18 years with at least 2 fasting blood sugar readings of &amp;gt;126 mg/dl or 2 post prandial readings of &amp;gt;200 mg/dl or need for antidiabetic medications beyond 1-month post-transplant were studied as PTDM or NODAT. Patients with deceased donor transplant, second kidney transplant, simultaneous other organ transplant, active Hepatitis C infection, active cytomegalovirus infection, patients with acute rejection, patients with polycystic kidney disease and patients with basiliximab induction were excluded. Results After applying exclusion and exclusion criteria, 98 patients were studied in total. Among 98 patients around 40 patients developed PTDM. When assessed independently higher age of the patient (age more than 50 years) was associated with PTDM (p = .030) while sex of the recipient was not associated with PTDM (P = .188). BMI &amp;gt;25 kg/m2 was significantly associated with PTDM at 1 month (p = .0001), 2 month (p &amp;lt; .0001), 3 month (p &amp;lt; .0001), 6 month (p &amp;lt; .0001), 9 month (p = .0001) and 12 month (p = .003) post-transplant. No statistical difference between doses of steroids were seen in patients with or without PTDM. All 98 patients received tacrolimus as part of their immunosuppressant regime. Time varying serum tacrolimus trough levels were not associated with PTDM and was removed as confounder by using univariate cox proportional hazard model (p = 0.691). After univariate and subsequently multivariate logistic regression analysis only hypomagnesemia was significantly associated with PTDM (p = .0001). After using univariate and subsequently multivariate cox proportional hazard model to study time varying risk factors, both hypomagnesemia (HR, 0.099; 95% CI, 0.016-0.624, p = .014) and BMI &amp;gt;25 kg/m2 (HR, 3.435; 95% CI, 1.657-7.119, p = .001) were associated with PTDM. Significantly a greater number of patients with lower magnesium levels developed PTDM early as compared to patients with normal magnesium levels (Spearman's coefficient of rank correlation (rho) = 0.53; 95% CI, 0.261-0.722, p = .0004). Conclusion Hypomagnesemia and overweight are modifiable risk factors significantly associated with PTDM even after removing confounding factors. Early development of PTDM in patient with hypomagnesemia further corroborates its role. Active interventions should be sought to control hypomagnesemia and overweight which may improve the morbidity and mortality of kidney transplant patients in long run.