Immunosuppressive Regimen Research Articles

The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation

An overview is provided of the evolution of strategies towards xenotransplantation during the past almost 40 years, focusing on advances in gene-editing of the organ-source pigs, pre-transplant treatment of the recipient, immunosuppressive protocols, and adjunctive therapy. Despite initial challenges, including hyperacute rejection resulting from natural (preformed) antibody binding and complement activation, significant progress has been made through gene editing of the organ-source pigs and refinement of immunosuppressive regimens. Major steps were the identification and deletion of expression of the three known glycan xenoantigens on pig vascular endothelial cells, the transgenic expression of human “protective” proteins, e.g., complement-regulatory, coagulation-regulatory, and anti-inflammatory proteins, and the administration of an immunosuppressive regimen based on blockade of the CD40/CD154 T cell co-stimulation pathway. Efforts to address systemic inflammation followed. The synergy between gene editing and judicious immunomodulation appears to largely prevent graft rejection and is associated with a relatively good safety profile. Though there remains an incidence of severe or persistent proteinuria (nephrotic syndrome) in a minority of cases. This progress offers renewed hope for patients in need of life-saving organ transplants.

The effect of the use of omeprazole versus famotidine on the kidney transplant function: a randomized controlled study

Tacrolimus is metabolized in the liver with the participation of cytochrome P450 isoforms 3A4 and 3A5 (CYP3A4, CYP3A5). Omeprazole, unlike famotidine, is a substrate and inhibitor of CYP2C19, CYP3A4, CYP3A5 enzymes. The aim of the study is to compare the effect of omeprazole and famotidine on the tacrolimus concentration and the kidney transplant function. A randomized study was conducted in 24 adult patients with stable kidney transplant function who received a standard triple immunosuppression regimen. Patients were assigned to the group I (n = 12) additionally receiving omeprazole (20 mg) or the group II (n = 12) receiving famotidine (20 mg). At the time of qualification and during follow-up visits, tacrolimus blood concentration and selected laboratory tests were performed. Statistical analysis was performed using the MedCalc system. The value of tacrolimus concentration in the blood increased after a year in the group I (7.27 ± 2.33 vs 9.20 ± 2.46 ng/mL, p = 0.0478). A reduction in tacrolimus dosage was observed after three years in the group I (3.56 ± 1.75 vs 2.78 ± 1.00 mg, p = 0.0440) and in the group II (2.72 ± 0.84 vs 2.10 ± 0.48 mg, p = 0.0051). There was significant difference in the percentage changes of glomerular filtration rate between the groups after 3 years of the study (− 5.56% vs 9.13%, p = 0.0343). Omeprazole significantly change the concentration of tacrolimus in the blood when administered together with tacrolimus after one year of observation. There was no effect of famotidine or omeprazole on the function of the kidney transplant. ClinicalTrials.gov identifier: NCT05061303.

Genetically engineered pig heart transplantation in non-human primates

BackgroundImprovement in gene modifications of donor pigs has led to the prevention of early cardiac xenograft rejection and significantly prolonged cardiac xenograft survival in both heterotopic and orthotopic preclinical non-human primate (NHP) models. This progress formed the basis for FDA approval for compassionate use transplants in two patients.MethodsBased on our earlier report of 9-month survival of seven gene-edited (7-GE) hearts transplanted (life-supporting orthotopic) in baboons, we transplanted 10 gene-edited pig hearts into baboons (n = 4) using non-ischemic continuous perfusion preservation (NICP) and immunosuppression regimen based on co-stimulation blockade by anti-CD40 monoclonal antibody. This pivotal study expands on the 7-GE backbone, with 3 additional gene edits, using 10-GE pigs as donors to baboon recipients.Results10 GE cardiac xenografts provide life-supporting function up to 225 days (mean 128 ± 36 days) in a non-human primate model. Undetectable or latent porcine cytomegalovirus (PCMV) does not influence cardiac xenograft survival in this study but still needs more exploration with a larger cohort. Xenograft histology demonstrates adipose (Fat) deposition (n = 1), chronic vasculopathy (n = 1), micro and macro thrombosis, and acute cellular rejection (n = 1).ConclusionsThese data demonstrate that 10 GE cardiac xenografts have variable cardiac xenograft survival in NHP due to perhaps presence of 4th antigen and require further study. However, these 10GE organs may be suitable for clinical cardiac xenotransplantation and have already been utilized in two human cases.

ABO incompatible living donor liver transplant novel immunosuppression regimen: a case series report

ABO incompatible living donor liver transplant novel immunosuppression regimen: a case series report

Syndecan-1 in the Serum of Deceased Kidney Donors as a Potential Biomarker of Kidney Function.

The process of kidney transplantation remains the optimal treatment for end-stage renal disease, offering improved quality of life and increased survival rates compared to long-term dialysis. However, despite advances in surgical techniques, immunosuppression regimens, and post-operative care, there are still significant challenges in predicting the organ's status and long-term outcomes of transplantation. Among the many factors that influence graft survival, the quality of the donated organ plays a fundamental role. There is an ongoing need for accurate and reliable biomarkers. Syndecan-1 is found in the endothelial glycocalyx and shed at a higher rate into the blood during systemic pathological conditions. The aim of this study is to evaluate the potential of serum syndecan-1 levels as a biomarker for assessing donor kidney quality and to investigate its correlation with donor characteristics and short-term outcomes in kidney recipients. We investigated serum syndecan-1 levels in 80 deceased donors and correlated them with donor characteristics and short-term outcomes (defined as delayed graft function - defined as the need for dialysis within the first week post-transplantation and renal function at 3 months post-transplantation - assessed using serum creatinine levels) in 104 corresponding kidney recipients. This single-center retrospective observational cohort study was conducted from April to December 2021. The donor pool consisted of 65% males with a median age of 53 years. Of these, 45 donors (56%) were classified as extended criteria donors. Higher syndecan-1 levels correlated with the last creatinine levels before organ procurement (R = 0.32, p = 0.01) and were marginally higher in donors with acute kidney injury (p = 0.07). However, syndecan-1 levels were not associated with short-term outcomes in kidney recipients (renal function at 3 months). The data suggests syndecan-1 could be a potential biomarker for assessing donor kidney quality, although its implications on recipient outcomes require further study. This pilot investigation underscores the importance of syndecan-1 in evaluating organ quality but highlights the necessity for more extensive research to validate these findings and explore their implications in transplant success.

Common Variable Immunodeficiency Associated With Noninfectious Pulmonary Complications and Its Treatment: Beyond Immunoglobulin Therapy.

Common variable immunodeficiency (CVID) is a type of primary immunodeficiency that presents as a heterogenous disorder characterized by hypogammaglobinemia, poor response to vaccines, recurrent sinopulmonary infections, and can have noninfectious systemic manifestations. We performed a single-center, retrospective, observational study of five patients with noninfectious complications of CVID. All patients had CVID as defined by the European Society of Immunodeficiencies criteria and had received intravenous immunoglobulin therapy. There were multiple pulmonary manifestations of CVID including frequent pneumonias, bronchiectasis, granulomatous lung disease, and pulmonary hypertension. All our patients were treated with pulmonary vasodilators for severe precapillary pulmonary hypertension along with individualized immunosuppression regimen for interstitial lung disease. Despite treatment for interstitial lung disease and PH, their conditions worsened over 2-3 years with all patients progressing toward organ transplant evaluation. Idiopathic thrombocytopenia and non-cirrhotic portal hypertension were common, with three patients probably suffering from nodular regenerative hyperplasia. Noninfectious complications of CVID can affect different organs and progress despite advanced therapies. Single or multiorgan transplantation is a treatment option for patients with end-stage organ involvement refractory to medical therapy.

Everolimus with or without mycophenolate mofetil for GVHD prophylaxis after allogeneic HSCT in children with acute kidney injury - a single-center retrospective analysis.

Hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute and chronic graft-versus-host disease (GVHD) are decisive determinants for allogeneic HSCT success. The immunosuppressive agent, ciclosporin A, is most often used to prevent GVHD in pediatric patients, but is known to be nephrotoxic. Acute kidney injury afflicts 21-84% of pediatric HSCT cases, compromising clinical outcomes. This retrospective single-institution analysis scrutinized the practice of substituting nephrotoxic ciclosporin A with an everolimus/mycophenolate mofetil combination as GVHD prophylaxis in 57 patients with acute kidney injury (n=53) or central nervous system side effects due to calcineurin inhibitor treatment (n=4) following first allogeneic HSCT. This retrospective cohort study analyzes clinical courses in 57 children switched from calcineurin inhibitor-based GVHD prophylaxis (ciclosporin A or tacrolimus in single cases) to the everolimus/mycophenolate mofetil combination (n=48) or everolimus alone (n=9) after first allogeneic HSCT at the Charité University Medicine Berlin. Serving as control cohort were 74 patients undergoing first allogeneic HSCT during the same period, who did not receive everolimus at any date post-transplantation. Patients undergoing mismatched family donor transplantation without subsequent calcineurin inhibitor treatment for GVHD prophylaxis were excluded. Study endpoints encompassed the retention parameter course subsequent to GVHD prophylaxis switch, overall survival, incidence of underlying disease relapse and acute and chronic GVHD in both treatment groups. Renal function significantly improved after switching from ciclosporin A treatment to the everolimus/mycophenolate mofetil combination. Crucially, the transition to everolimus did not adversely affect overall survival following HSCT (HR 1.6; 95% CI: 0.74 - 3.5; p=0.23), especially for patients afflicted with non-malignant diseases (HR 1.4; 95% CI: 0.34 - 5.9; p=0.64). Incidences of grade 3-4 acute GVHD (HR: 1.82; 95% CI: 0.45 - 7.4; p=0.40) and severe chronic GVHD (HR 2.76, 95% CI: 0.69 - 11.0; p=0.15) in patients treated with the everolimus/mycophenolate mofetil combination were comparable to standard ciclosporin A treatment in patients in the control group. Overall survival in patients with malignant underlying diseases was lower in the everolimus cohort (HR: 2.7; 95% CI: 1.1 - 6.9, P=0.03), however, event-free survival was similar in patients with an underlying malignant disease, who were treated with either the everolimus/mycophenolate mofetil combination or ciclosporin A (HR 0.87, 95% CI: 0.39-1.9, p=0.73). Among patients who switched immunosuppression regimen from cyclosporin A to everolimus, with or without mycophenolate mofetil co-treatment after diagnosis of AKI, renal function significantly improved. Patient outcomes in the everolimus cohort were comparable to those in the control cohort. This study provides compelling real-world clinical evidence to replace ciclosporin A with the everolimus/mycophenolate mofetil combination in the management of acute kidney injury following HSCT in children.

Practical Management of ANCA-associated Vasculitis – A Clinician’s Perspective

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can be a life-threatening condition, characterised by necrotising inflammation of small blood vessels. Major organ involvement, most commonly kidney and lung disease, is associated with significant morbidity and mortality. Intensive early immunosuppressive therapy is the cornerstone of management and has transformed ANCA-associated vasculitis (AAV) into a chronic relapsing condition. Remission induction with tapering glucocorticoids in combination with cyclophosphamide or rituximab is the standard of care for severe disease. Avacopan, an oral C5aR1 antagonist, has been approved for remission induction and helps minimise glucocorticoid exposure. Plasma exchange should be considered for severe kidney or life-threatening disease. Lower dose glucocorticoid induction regimens can be used without compromising remission rates. Remission maintenance therapy is recommended, and rituximab is usually first line over azathioprine. Mycophenolate mofetil (MMF) or methotrexate with low dose glucocorticoids are third line options. Immunosuppression associated infection risk remains a concern; both during acute presentations and in the long term; highlighted by the impact of rituximab on humoral immunity and vaccine response during the COVID-19 pandemic. There remains an ongoing need for therapies which induce rapid remission and optimise kidney recovery whilst minimising infection risk. Clinical trials are evaluating newer therapeutic options. Due to increasing treatment options, management should be individualised, balancing effective immunosuppression against co-morbidities and frailty. Summary: This review focuses on the treatment decision pathways for clinicians and patients in the management of severe AAV (granulomatosis with polyangiitis and microscopic polyangiitis). Key clinical trials, predictors of outcome, novel therapeutics and practical steps to mitigate infection risk are discussed. Key messages: Immunosuppression regimens have been refined due to emerging evidence from clinical trials. Rituximab, avacopan and reduced-dose glucocorticoid schedules have been the focus of recent studies. Infections and immunosuppression-induced immunodeficiency must be considered when determining individualised treatment.

Key challenges of post-liver transplant weight management.

Liver transplantation serves as a life-saving intervention for patients with end-stage liver disease, yet long-term survival remains a challenge. Post-liver transplant obesity seems to have a significant contribution to this challenge and it emerges as a significant risk factor for graft steatosis, metabolic syndrome and de-novo malignancy development. This review synthesizes current literature on prevalence, risk factors and management strategies for post-liver transplant obesity, emphasizing its impact on graft and patient survival. Literature review consultation was conducted in Medline/PubMed, SciELO and EMBASE, with the combination of the following keywords: Weight management, liver transplantation, immunosuppressive therapy, lifestyle interventions, bariatric surgery. Immunosuppressive therapy has a significant influence on long-term survival of liver transplant patients, yet it seems to have lesser effect on post-transplant obesity development than previously thought. However, it significantly contributes to the development of other components of metabolic syndrome. Key predisposing factors for post-transplant obesity development encompass elevated recipient and donor body mass index, a history of alcoholic liver disease, hepatocellular carcinoma, male gender, the absence of cellular rejection and the marital status of the recipient. Tailored immunosuppressive regimens, pharmacotherapy, lifestyle interventions and bariatric surgery represent key components in mitigating post-transplant obesity and improving long-term survival and quality of life in this group of patients. Timely identification and intervention thus hold paramount importance. Further research is warranted to refine optimal management strategies and enhance outcomes in this patient population.

Retention of indoxyl sulfate in different genotypes of ABCC2 may explain variation in tacrolimus pharmacokinetics.

Microbiota-derived toxins indoxyl sulfate and hippuric acid were previously reported to be associated with altered pharmacokinetics of the immunosuppressant tacrolimus in liver transplant recipients, and ABC transporter proteins are likely to be involved in the transport of such substances, but the in vivo role has not been elucidated. The aim of this study was to assess the retention of indoxyl sulfate and hippuric acid in the plasma of liver transplantation subjects carrying different genotypes of ABCB1 and ABCC2 (changes in transporter activity due to genetic variation), and to explore whether genetic variation is involved in altering the relationship between microbe-derived toxins and tacrolimus pharmacokinetics. Liver transplantation subjects treated with the immunosuppressive regimen tacrolimus, corticosteroids, and mycophyolate mofetil were included and divided into normal renal function group and chronic kidney disease group. The plasma concentrations of indoxyl sulfate and hippuric acid in two groups of liver transplantation subjects carrying different genotypes of ABCB1 and ABCC2 were compared. For genotype carriers with significant differences, the Pearson Correlation Coefficient method was further used to investigate the correlation between plasma indoxyl sulfate level and tacrolimus dose-corrected trough concentration in patients with different renal function status. Carriers of the rs717620-24T variant exhibited high plasma indoxyl sulfate retention in patients with normal renal function, and furthermore, chronic kidney disease patients and patients with normal renal function exhibited indoxyl sulfate and tacrolimus in the ABCC2 normal function (β = -0.740, p = 0.020) and reduced function groups (β = -0.526, p = 0.005), respectively, showing a strong correlation with tacrolimus. ABCC2 may be one of the pathways by which tacrolimus pharmacokinetics is altered by indoxyl sulfate.

A Half-Century of Heterotopic Heart Transplantation in Mice: The Spearhead of Immunology Research

Since the success of solid organ transplants, such as human kidneys, livers and hearts, from the 50s to the 60s in the last century, the field of organ transplantation has progressed rapidly. Mainly due to modifications in surgical operation techniques and improvements in immunosuppressive therapy regimes, organ survival time can now be greatly prolonged. This progress has also been dependent upon the availability of appropriate animal models for organ transplantation. Therefore, the mouse heart transplantation model has developed into an irreplaceable research model for solid organ transplantation, providing indelible contributions to the field. In this review, we will provide an overview of the technical developments in murine heart transplantation, as well as its historical and current role for alloimmune research. Further, we will describe its current fields of application and its scientific achievements before we discuss potential future applications.

Immune checkpoint inhibitors in the posttransplant landscape of HCC: A systematic literature review.

Immune checkpoint inhibitors (ICIs) have shown promise in the treatment of HCC. However, their safety and efficacy in recipients of liver transplants with recurrent HCC remain unclear. This systematic review aims to evaluate the use of ICIs for recurrent HCC after liver transplantation (LT) and to identify potential predictive factors associated with graft rejection and treatment response. A comprehensive literature search was conducted using PubMed and Scopus databases to identify case reports and case series describing the use of ICIs for HCC recurrence after LT. Data on patient characteristics, treatment details, and outcomes were extracted and analyzed. Twenty-one case reports and case series involving 39 patients were included. The median time from LT to ICI initiation was 24 months. Nivolumab was the most commonly used ICI (59.0%). Among all cases, 25.6% demonstrated a positive response, including stable disease and partial or complete response, while 46.2% experienced progressive disease. Graft rejection occurred in 20.5% of patients, with 50% of these cases resulting in death. Although reported in only some of the cases (17 out of 39), positive programmed cell death ligand-1 expression was associated with a higher risk of graft rejection (66.7%) compared to negative expression (0%). calcineurin inhibitors-based immunosuppressive regimens appeared to have lower rejection rates (20%) compared to mammalian target of rapamycin inhibitor-based regimens (80%). ICIs show potential for treating recurrent HCC after LT, but the risk of graft rejection is significant. Careful patient selection, close monitoring, and individualized management of immunosuppression are crucial. Positive programmed cell death ligand-1 expression and the choice of immunosuppressive regimen appear to influence the risk of graft rejection; however, these findings are based on limited data. Prospective studies with larger sample sizes are needed to validate these findings and establish evidence-based guidelines for the use of ICIs in the posttransplant setting.

Prostate cancer in solid organ transplant recipients: results from a multicenter series

Prostate cancer incidence in immunosuppressed transplant recipients increases as life expectancy improves in this population. However, the management of treatments and immunosuppressive (IS) regimens for solid organ transplant recipients diagnosed with prostate cancer remains poorly defined. Therefore, we conducted a multicentric study to investigate these parameters more thoroughly. This multicentric, retrospective study includes all kidney, heart, liver, or combined transplant recipients, diagnosed with prostate cancer between 1998 and 2020. IS regimen management, demographic, oncological and survival outcomes were studied here. A prostate cancer was diagnosed among 87 SOTRs: 70 RTRs, 10 HTRs, 2 LTRs and 5 combined transplant recipients. The mean age at diagnosis was 64.3years with 10.7years mean time from transplantation to PCa. A 38% low risk, 45% intermediate risk and 11% high risk were recorded at diagnosis. Fifty-six patients underwent radical prostatectomy, 11 patients underwent radiotherapy combined with ADT, 4 patients underwent radiotherapy alone, 6 patients underwent ADT alone, 1 patient underwent brachytherapy, 3 patients underwent watchful waiting, 1 patient was treated by HIFU and 5 patients were under active surveillance. Sixteen patients had complementary treatment following biochemical recurrence or positive margins. IS regimen was modified for 69% of patients. Twelve deaths occurred in total (14%) with a 92% and 86%, 3- and 5-year overall survival respectively. Three- and 5-year progression-free survival were 89% and 83% respectively. There was no significant PFS difference between patients treated with radiotherapy and prostatectomy (P=0.94), and patients with or without a change in immunosuppressants (P=0.88). Guidelines for diagnosis and management of prostate cancer in the general population appears to apply in SOTRs with good oncological outcomes. Active surveillance should also be considered in this population. Low.

Immunotherapy for Cancer in Kidney Transplant Patients: A Difficult Balance Between Risks and Benefits.

Cancer is a major cause of morbidity and mortality in kidney transplant patients. Unfortunately, the use of new anti-cancer therapies such as immune checkpoint inhibitors (ICPIs) in this population has been associated with rejection rates up to 40%, in retrospective studies. The main challenge is to maintain the patient in a delicate immunologic balance in which, while antitumor therapy defeats cancer the graft is safely protected from rejection. Recent clinical trials with ICPI have included kidney transplant recipients (KTRs) and the results advocate for a paradigm shift in the management of basal immunosuppression. This suggests that downward adjustments should be avoided or, even better, that this adjustment should be "dynamic." This review summarizes the latest scientific evidence available in renal transplantation under ICPI treatment: case series, prospective studies, histopathologic diagnosis, immunosuppression regimens and new biomarkers. This article will provide the latest information in on this specific field, allowing nephrologists to gain valuable knowledge and to be aware of new approaches to immunosuppression management in oncological kidney transplant patients.

Prior immunity to Ureaplasma urealyticum protects against respiratory infection in immunosuppressed mice.

Ureaplasma species can cause systemic infections in immunocompromised hosts, including lung transplant recipients. Here, we investigated the impact of prior exposure to Ureaplasma urealyticum on the risk of U. urealyticum and Ureaplasma parvum infection in mice subjected to an immunosuppression regimen similar to that administered to solid organ transplant recipients. Mice were immunized with three intramuscular injections of U. urealyticum, with control mice injected with adjuvant only. Following immunization, mice received tacrolimus, mycophenolate mofetil, and methylprednisolone, and then were challenged with U. urealyticum or U. parvum intraperitoneally and intratracheally over 6 days. Relative U. urealyticum antibody levels in plasma were assessed over time, and lungs were harvested at sacrifice for bacterial load quantification, assessed using a color-changing unit assay. U. urealyticum antibody levels were higher in immunized compared with control animals (P < 0.0001), even when animals were immunosuppressed. U. urealyticum and U. parvum lung burden was reduced in immunized compared with control mice (~6 log10 reduction for U. urealyticum and <1 log10 reduction for U. parvum; P = 0.008 and 0.046, respectively). In summary, this study shows that prior exposure to live U. urealyticum provides some protection against infection with U. urealyticum.IMPORTANCEUreaplasma-induced hyperammonemia syndrome is a rare but potentially deadly complication of solid organ transplantation, especially lung transplantation. The pathophysiology of this relatively recently recognized condition is poorly understood, and it is unclear what factors may influence patient susceptibility. This study investigates the possible protective effects of prior exposure to Ureaplasma urealyticum in a mouse model subjected to an immunosuppression regimen similar to that given to lung transplant recipients. The findings show that prior exposure could provide protection against Ureaplasma lung infection.

Parathyroid allotransplantation for severe post-surgical hypoparathyroidism: a Brazilian experience.

This study presents the cases of two women who developed severe permanent hypoparathyroidism after neck surgery for papillary thyroid cancer and underwent parathyroid allotransplantation. Despite taking high doses of calcium and calcitriol supplements, the patients experienced persistent hypocalcemic symptoms. Fresh parathyroid tissue was removed and prepared from two patients with hyperparathyroidism secondary to end-stage kidney disease and was implanted in the non-dominant forearm of the recipients. Donors and recipients were ABO-compatible, and immunological screening was performed only in Case 2 (HLA typing, panel reactive antibody, and crossmatch tests). A short-term immunosuppressive regimen was adopted, consisting of 3days of methylprednisolone followed by 7days of prednisone. In Case 1, oral supplementation decreased to half of the initial dose 1month after transplantation and to one-fifth at the end of a 12-month follow-up period. In Case 2, intravenous calcium was discontinued 1-week post-transplantation, with no need for its use during the 12-month follow-up period. Serum parathyroid hormone levels did not increase and remained undetectable in both cases. In contrast, serum calcium levels increased significantly, and both patients experienced relief from hypocalcemic symptoms. Parathyroid allotransplantation can be an effective and safe treatment for PH and should be considered in severe cases. Nevertheless, formal recommendations depend on additional studies and validated protocols.

Precision in Immune Management: Balancing Steroid Exposure, Rejection Risk, and Infectious Outcomes in Adult Kidney Transplant Recipients.

With kidney transplant immunosuppression, physicians must balance preventing rejection with minimizing infection and malignancy risks. Steroids have been a mainstay of these immunosuppression regimens since the early days of kidney transplantation, yet their risks remain debated. Our study looks at the clinical outcomes of patients undergoing early steroid withdrawal (ESW) vs. steroid continuous (SCI) maintenance immunosuppression in adult kidney transplant recipients. A retrospective case-control study, utilizing propensity score-matching, was performed using the US Collaborative Network Database within TriNetX to evaluate renal transplant outcomes at one year in first-time kidney transplant adult patients (>18 years old) who were prescribed an ESW regimen (no steroids after post-transplant day 7 with maintenance tacrolimus [tac] + mycophenolic acid [MMP]/mycophenolate mofetil [MMF]) vs. SCI (tac + MMF/MMP + prednisone). Cohorts were matched on demographics, comorbidities, previously described risk factors for rejection, and induction immunosuppression. Primary outcomes included viral infections, pyelonephritis, and sepsis. Secondary outcomes included renal transplant rejection, death-censored allograft failure (eGFR < 15 mL/min), patient mortality, delayed graft function, and diabetes mellitus. A total of 2056 patients were in each cohort after matching (mean age: 50.7-51 years, 17.9-20.0% African American, 60-60.6% male.) The SCI cohort had a significantly higher cumulative incidence of composite viremia (18 vs. 28.1%, ESW vs. SCI, p < 0.01) driven by CMV, EBV, and BK virus. Post-transplant diabetes mellitus was significantly higher in the SCI cohort (3.21% vs. 5.49%, ESW vs. SCI, p < 0.01). Delayed graft function was also higher in the SCI cohort (19.55% vs. 22.79%, ESW vs. SCI, p < 0.01). Pyelonephritis (2.3 vs. 4.91%, ESW vs. SCI, p < 0.01) and sepsis (2.15 vs. 5.95%, ESW vs. SCI, p < 0.01) were higher in the SCI cohort. Rejection rates were similar between ESW and SCI (29 vs. 31%, ESW vs. SCI, p = 0.41). There were significantly higher incidences of graft failure (4.9 vs. 9.9%, ESW vs. SCI, p < 0.01) and mortality (0.8 vs. 2.1%, ESW vs. SCI, p < 0.01) in the SCI cohort. This well-matched case-control study suggests that ESW is associated with lower infectious outcomes, mortality, and graft failure without increasing rejection risk, supporting the potential benefits of ESW in kidney transplant patients.

Abstract 4121816: Viral Venture: A Case of Myocarditis and IgA Vasculitis from Adenovirus Infection

Case Description: A 19-year-old man presented to the emergency department for 3 days of shortness of breath, progressive bilateral lower extremity rash, generalized fatigue, and diffuse joint following an earlier visit to urgent care for pharyngitis symptoms. Physical exam was notable for tachycardia, pain with active wrist and ankle range of motion, pharyngeal erythema, cervical adenopathy, and confluent erythematous palpable purpura and petechiae noted on bilateral lower extremities with scattered lesions on his thighs, arms, and back. Laboratory workup notable for markedly elevated high-sensitivity troponin to 3398 ng/L, and elevated CRP. Further workup was notable for normal urinalysis, negative streptococcus antigen, negative ANCA antibodies, ANA, Hepatitis B and C, and cryoglobulins. Imaging and cardiac workup were notable for normal left ventricular function and cardiac MRI notable for late gadolinium enhancement in the anteroapical mid-myocardial region suggestive of myocarditis. Skin biopsy ultimately revealed immunodeposition of IgA on superficial capillaries compatible with a diagnosis of IgA vasculitis. The patient was started on steroids for IgA vasculitis with rapid improvement in his symptoms and he was discharged home in good condition. Discussion: Recognizing the severe complications of viral infection can lead to prompt treatment and prevention of progression to severe end organ damage. Our case highlights rarely reported cardiac involvement of IgA vasculitis secondary to adenovirus infection based on laboratory and imaging diagnosis with cardiac MRI. To date, only 16 cases of cardiac involvement in IgA vasculitis have been reported. This case adds to the limited body of published cases describing this presentation of IgA vasculitis and is also consistent with the results of prior cases suggesting that an immunosuppressive regimen including glucocorticoids may help to prevent disease progression and induce remission in cases with cardiac involvement without the need for endomyocardial biopsy.

Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS

IntroductionHigh-dose glucocorticoid (GC)-based dual immunosuppressive treatment regimens are still frequently used in active lupus nephritis (LN) despite their known association with dose-dependent toxicities and incomplete efficacy. We hypothesised that the...

Beyond Borders: International Immunosuppression Practices in Pediatric Lung Transplantation.

Current recommendations for lung transplantation immunosuppression do not explicitly target children, and many pharmacotherapies used in pediatrics are extrapolated from adults. Data were collected from an anonymous survey distributed to International Pediatric Lung Transplant Collaborative (IPLTC) members from November 2023 to February 2024. Eligible participants included pediatric lung transplant physicians, pharmacists, or others with expertise in their lung transplant center's protocols. Participant and program demographics were surveyed, including location and transplant volume. Seventeen multiple-choice questions, text responses, and Likert scale statements covered the following: induction immunosuppression, maintenance immunosuppression, drug monitoring, dose optimization, and expert guidance available in current literature. Among the 23 pediatric lung transplant healthcare professionals who responded, 13 respondents (57%) preferred using basiliximab as their standard induction immunosuppression. 3 (13%) prefer rabbit anti-thymocyte globulin (rATG), while 7 (30%) consider either rATG or basiliximab for induction. Of 22 responses with 100% completion, 21 of 22 (95.2%) respondents reported a combination of tacrolimus, mycophenolate mofetil (MMF), and corticosteroids (CCS) as their preferred maintenance immunosuppression regimen, reflecting the suggested preferred regimen for pediatric lung transplantation. Feedback on theperception of available evidence-based or established guidelines revealed the majority (90.0%) of respondents found them to be insufficient for pediatrics. This international survey highlights thevariability in immunosuppression practices across pediatric lung transplant programs around the world. The findings underscore a gap in unified, evidence-based practice guidelines. With strong consensus among respondents on the lack of established guidelines, there is aclear directive for future research to establish standardized practices in pediatric lung transplantation.