Immunosuppressive Management Research Articles

Evolution of HLA-sensitization according to immunosuppressive therapy management among kidney transplant patients returning to dialysis between 2008 and 2019: A French retrospective study.

The optimal management of immunosuppressive therapy (IT) after kidney allograft failure (KAF) remains controversial. Although maintaining IT may reduce HLA-sensitization and improve access to retransplantation, it may also increase the rate of immunosuppression-related complications. The overall impact on patient mortality is unknown. The main objective of this study was to compare the evolution of HLA-sensitization 6months after KAF according to IT management. Individual clinical and health care data were extracted from the French national end-stage kidney disease registry (Renal Epidemiology and Information Network [REIN]) and the French National Health Data system (SNDS), respectively. Patients aged>18years returning to dialysis after KAF between January 2008 and December 2019 in Lorraine were included. Patients were classified into two groups, IT continuation or IT discontinuation. HLA-sensitization was defined as an increase in incompatible graft rate (IGR) between KAF and 6months post-KAF (change to a higher predefined category (0%-5%), (5%-20%), (20%-50%), (50%-85%), (85%-95%), (95%-98%), (98%-100%)). Secondary outcome was patient survival according to IT management. A total of 121 patients were included, 35 (29%) of whom continued IT. HLA-sensitization after KAF tended to be higher in the "IT discontinuation" group (57%vs. 38% in the "IT continuation" group, p=.07). In multivariate analysis, IT continuation was associated with a lower increase in IGR (OR .37, 95% CI [.14; .93]). IT management was not associated with patient mortality. Continuation of IT after KAF was associated with less change in IGR and was not associated with excess mortality.

Delivery of gene therapy in haemophilia treatment centres in the United States: Practical aspects of preparedness and implementation.

Haemophilia treatment centres (HTCs) and healthcare providers (HCPs) will need to adapt to a new treatment paradigm with the emergence of adeno-associated virus (AAV)-based gene therapy for the treatment of haemophilia in adults. This review examines the upcoming patient and institutional journeys, along with practical aspects of preparedness for clinical delivery of gene therapy by HTCs. Based on our clinical experience and examination of published literature, we explored the parallel journeys for patients and treatment centres to navigate before, during, and after administration of gene therapy. The patient journey includes: information gathering; decision making; comprehensive patient assessment; preparation for the infusion itself; short- and long-term monitoring; lifestyle modifications; and the possible need for immunosuppressive treatment. Informed decision-making may require patient education with extensive discussions and an understanding that not all people with haemophilia will choose or be eligible for gene therapy, although eligibility criteria continue to evolve. The institutional journey includes: consideration of biosafety procedures; planning for product procurement, handling, storage, and administration; development of detailed protocols and guidance documents; contingency planning for immunosuppressive and haemostatic management; consideration of clinical capabilities and staff training needs; coordination of efforts by the full multidisciplinary team; and collaboration between referring, dosing, and follow-up treatment centres. Documented protocols and guidance documents are pivotal for this complex therapy to ensure safe handling, optimal delivery, and post-infusion management and follow-up. Successful implementation of this new treatment modality will require communication and collaboration among multiple stakeholders.

Study of the Effect of ABCB1 Single Nucleotide Polymorphism on Tacrolimus Dose Requirements in Liver Transplant Patients

Abstract Background Liver transplantation (LT) is the only effective radical cure for all types of end stage liver diseases. Major advances have been made in the field of liver transplantation due to improvements in surgical techniques and organ conservation as well as optimization of intensive care and immunosuppressive management. Aim of the Work The aim of the present work is to assess the influence of ABCB1 gene polymorphism of liver transplant recipients on blood level and dose requirements of oral tacrolimus, in an attempt to help in designing an individualized tacrolimus regimen for Egyptian liver transplant recipient. Patients and Methods The study included 25 liver transplant recipients and their respective donors. All subjects of this study were subjected to full medical history, Clinical evaluation, Laboratory investigations, and ABCB1 gene polymorphism evaluation by RT-PCR. Tacrolimus trough level was evaluated for all the recipients during the first 3 months post transplantation. Results The present study revealed that the presence of CC genotype was significantly correlated to the effect on tacrolimus C/D ratio and Weight adjusted tacrolimus dose during the first week of the first and 2nd month (Z = -2.108, P < 0.05) but not the 3rd month post transplantation (p-value >0.05). Subjects carrying CC genotype required higher doses of tacrolimus to achieve the desired trough levels compared to subjects carrying CT and TT genotypes. The same effect was observed over the whole period of the study but the results were statistically non-significant (p-value>0.05). Recipients who received liver tissue from donors carrying CC genotype also required higher doses of tacrolimus and reached lower levels of blood tacrolimus trough levels. Conclusion The present study revealed that ABCB1 CC genotype of both recipients and donors of liver transplantation was significantly associated with increased required tacrolimus dose early after liver transplantation reaching statistically significant level in the first week of the first and second months.

Impact of COVID-19 on renal transplant recipients

Introduction: It was essential to explore immunosuppressant management strategies and potential clinical variables associated with COVID-19 related mortality in order to provide insight for clinicians attempting to manage kidney transplant recipients during the ongoing severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic. Objectives: The aim of the study was to assess the impact of COVID-19 on post-transplant renal function and outcome of immunosuppressant management on COVID-19. Patients and Methods: This is a cross sectional observational study conducted from March 2020 to January 2022 in a tertiary care hospital in South India. Baseline characteristics, comorbidities, history of graft dysfunction, symptoms and immunosuppressant modification was noted. Outcomes of COVID-19 such as acute kidney injury (AKI), need for dialysis and post COVID-19 complications were noted. The statistics were expressed as percentage for categorical variables and mean ± SD for continuous variables. Results: Out of 400 renal transplant patients on regular follow up, 28 patients developed COVID-19. The incidence of AKI was 64.2%. Immunosuppressant dose modification was done in majority of patients [mycophenolate mofetil (28.5%), steroids (53.5%) and tacrolimus (39.2%)]. Outcomes included recovery from AKI in 61.1%, recovery from oxygen dependence in 100% patients with an overall mortality rate of 7.1% patients. About 17.8% patients developed post-COVID-19 complications. Conclusion: Immunosuppressant dose modification during COVID-19 could play a role in development of AKI; infection being an independent risk factor. Patients should be monitored for development of post-COVID-19 complications.

Risk factors for infection in patients with a failed kidney allograft on immunosuppressive medications.

Patients with a failing kidney allograft are often continued on immunosuppression (IS) to preserve residual kidney function and prevent allosensitization. It has been previously accepted that maintaining patients on immunosuppressive therapy results in an increased risk of infection, hospitalization, and mortality. However, as the management of IS in patients with a failed kidney allograft continues to evolve, it is important to review the data regarding associations between infection and specific immunosuppression regimens. We present a review of the literature of failed kidney allograft management and infection risk, and discuss practices for infection prevention. Fifteen studies, published from 1995 to 2022, which investigated the experience of patients with failed allograft and infection, were identified. Infection was most commonly documented as a general event, but when specified, included infections caused by Candida, Mycobacterium tuberculosis, and Aspergillus. In addition, the definition of reduced "IS" varied from decreased doses of a triple drug regimen to monotherapy, whereas others did not specify which medications patients were receiving. Despite attempts at lowering net immunosuppression, patients with failed allografts remain at risk of acquiring opportunistic and non-opportunistic infections. Although opportunistic infections secondary to IS are expected, somewhat surprisingly, it appears that the greatest risk of infection may be related to complications of dialysis. Therefore, mitigating strategies, such as planning for an arteriovenous (AV) fistula over a hemodialysis catheter placement, may reduce infection risk. Additional studies are needed to provide more information regarding the types and timing of infection in the setting of a failed kidney allograft. In addition, more data are needed regarding specific medications, doses, and timing of taper of IS to guide future patient management and inform strategies for infection surveillance and prophylaxis.

Management of immunosuppressive therapy in kidney transplant recipients with COVID-19. A multicentre national study derived from the Spanish Society of Nephrology COVID registry

IntroductionSARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. ObjectivesEvaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. Material and methodsRetrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. Resultsrenal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years.The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased.Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 ± 0.8, 2.1 ± 1.2 and 1.8 ± 1 mg/dl respectively (p < 0.001).56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. ConclusionsThe management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.

The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants.

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was considered less of a concern. For the initial approach to immunosuppression reduction, 60% stop antimetabolites first, and 26% defer to the transplant nephrologist. Communicating with transplant centers about immunosuppression cessation was reported to occur always by 60%, and sometimes by 29%, while 12% reported making the decision independently. Nephrologists with academic appointments communicate with transplant providers more than private nephrologists (74% vs. 49%, p = 0.015). There are heterogeneous approaches to the care of patients with a failing allograft. Efforts to strengthen transitions of care and to develop practical practice guidelines are needed to improve the outcomes of this vulnerable population.

Circulating biomarkers in perioperative management of cancer patients

Abstract Owing to the advances in surgical technology, most solid tumours can be controlled by surgical excision. The priority should be tumour control, while some routine perioperative management might influence cancer progression in an unnoticed way. Moreover, it is increasingly recognized that effective perioperative management should include techniques to improve postoperative outcomes. These influences are elucidated by the different functions of circulating biomarkers in cancer patients. Here, circulating biomarkers with two types of clinical functions were reviewed: (i) circulating biomarkers for cancer progression monitoring, for instance, those related to cancer cell malignancy, tumour microenvironment formation, and early metastasis, and (ii) circulating biomarkers with relevance to postoperative outcomes, including systemic inflammation, immunosuppression, cognitive dysfunction, and pain management. This review aimed to provide new perspectives for the perioperative management of patients with cancer and highlight the potential clinical translation value of circulating biomarkers in improving outcomes.

238-OR: Changes In Renal Function after Islet Transplantation in a Single-Centre Cohort in Canada over 20 Years

Islet transplantation (ITx) is an established treatment for recurrent, severe hypoglycemia in type 1 diabetes, but requires lifelong immunosuppression (IS) which can be nephrotoxic. We examined long term changes in renal function after ITx, through estimated GFR (eGFR), in a single centre cohort followed for up to 20 years. We used data from adults undergoing islet after kidney or ITx alone (94%) at the University of Alberta Hospital between March 11 1999 and Oct 1 2019 with &amp;gt;1 year of follow up. IS included tacrolimus and sirolimus/mycophenolate, balancing side effects with graft and renal function. We calculated individuals mean CKD EPI eGFR (ml/min/1.73m2) at baseline (≤1y pre transplant), 6m and yearly timepoints across follow up. We assessed the overall slope/year of eGFR against time from first transplant in 3 time periods; ≤1y, 1-5y and 5-20y, using mixed effects models. We also compared slopes between subjects with preserved (&amp;gt;60, n=217) vs. reduced (&amp;lt;60, n=38) eGFR at baseline. We included 255 adults (42% M) followed for 88.3m [50.2, 144.9] (median [IQR]). Whole cohort eGFR declined over follow up, most rapidly in the first year; -28.3 [-31.8, -24.5], with slower decline later post transplant 1-5y; -2.9 [-3.5, -2.3] and 5-20y; -1.2 [-1.4, -1.04]. Those with preserved baseline eGFR experienced steeper decline across all time phases as compared to those with reduced eGFR, with the steepest decline ≤1y post transplant (-29.8 [-33.8, -25.9], -18.3 [-27.8, -8.9], p=0.027). Between 5-20y post transplant renal function continued to decline slowly in those with preserved baseline eGFR but was stable in those with reduced baseline eGFR, (-1.4 [-1.6, -1.2], 0.2 [-0.3, 0.7] p&amp;lt;0.001). Nine (3.5%) developed ESRD. Initiation of IS associates with a rapid decline in eGFR the first year post ITx, with minimal decline beyond 5y. With careful IS management, rates of eGFR decline are not greater in those with reduced baseline eGFR. Effective IS regimens without nephrotoxicity remain an important goal. Disclosure A.L.J.Carr: None. A.Shapiro: n/a. P.A.Senior: Advisory Panel; Novo Nordisk Canada Inc., Consultant; Novo Nordisk Canada Inc., Bayer Inc., Viatris Inc., Vertex Pharmaceuticals Incorporated, ViaCyte, Inc., Insulet Corporation. B.A.Marfil-garza: None. Y.Ling: None. R.A.Oram: Consultant; Janssen Research &amp; Development, LLC, Research Support; Randox R &amp; D. A.Lam: None. B.L.Anderson: None. D.O'gorman: None. T.Kin: None. D.Bigam: None.

Immune Checkpoint Inhibitors in Solid Organ Transplant Recipients With Advanced Skin Cancers-Emerging Strategies for Clinical Management.

Use of immune checkpoint inhibitors (ICIs) in solid organ transplant recipients (SOTRs) with advanced skin cancers presents a significant clinical management dilemma. SOTRs and other immunosuppressed patients have been routinely excluded from ICI clinical trials with good reason: immune checkpoints play an important role in self- and allograft-tolerance and risk of acute allograft rejection reported in retrospective studies affects 10% to 65% of cases. These reports also confirm that cutaneous squamous cell carcinoma and melanoma respond to ICI therapy, although response rates are generally lower than those observed in immunocompetent populations. Prospective trials are now of critical importance in further establishing ICI efficacy and safety. However, based on current knowledge, we recommend that ICIs should be offered to kidney transplant recipients with advanced cutaneous squamous cell carcinoma, melanoma, or Merkel cell carcinoma if surgery and/or radiotherapy have failed. For kidney transplant recipients, this should be first line ahead of chemotherapy and targeted therapies. In SOTRs, the use of ICIs should be carefully considered with the benefits of ICIs versus risks of allograft rejection weighed up on a case-by-case basis as part of shared decision-making with patients. In all cases, parallel management of immunosuppression may be key to ICI responsiveness. We recommend maintaining immunosuppression before ICI initiation with a dual immunosuppressive regimen combining mammalian target of rapamycin inhibitors and either corticosteroids or calcineurin inhibitors. Such modification of immunosuppression must be considered in the context of allograft risk (both rejection and also its subsequent treatment) and risk of tumor progression. Ultimately, a multidisciplinary approach should underpin all clinical decision-making in this challenging scenario.

#4960 TIXAGEVIMAB AND CILGAVIMAB (EVUSHELD) FOR PRE-EXPOSURE PROPHYLAXIS OF COVID-19: A MONOCENTRIC STUDY IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Patients, who underwent kidney transplantation, may be at particularly high risk of mortality due to immunosuppressive therapy and underlying comorbidity such as hypertension, cardiovascular disease and diabetes mellitus finally increasing the risk of a severe form of SARS-CoV-2 infection. According to the ERA-EDTA DESCARTES expert opinion, management of immunosuppression in SARS-CoV-2 infection suggests withdrawal of antimetabolite (mycophenolate or azathioprine) in patients with mild upper respiratory and/or gastrointestinal symptoms and discontinuation of all immunosuppressive drugs with maintenance of steroid for severe bilateral pneumonia. Despite SARS-CoV-2 vaccination, kidney transplant patients remain at increased risk for severe COVID-19 infection and mortality and at high priority for additional strategies for preexposure prophylaxis.Tixagevimab and cilgavimab are long-acting monoclonal antibodies against the spike protein of SARS-CoV-2, which block the virus’ attachment and entry into human cells. This combined monoclonal antibody (Evusheld®) has been granted emergency use authorization (EUA) by the U. S food and drug administration (FDA) for individuals 12 years and older who have a moderate to severe immunocompromising condition and may not mount an adequate vaccination response.This single cohort observational study reports the incidence and outcomes of COVID-19 among kidney transplant recipients receiving Evusheld® as preexposure prophylaxis. Method Observational monocentric cohort study of 119 kidney transplant patients receiving Evusheld® 150/150 mg intramuscularly as preexposure prophylaxis between July 1, 2022 and December 31, 2022. Inclusion criteria: kidney or combined kidney-pancreas transplantation within 1 year; recent acute allograft rejection; time since COVID-19 infection of 120 days and time since last vaccine dose of 2 weeks. Results After a median (range) follow-up of 150 days, COVID-19 was confirmed in 48/119 patients (40.3%), who had only a light form of COVID-19 infection. No one complained side. Conclusion Our study reported a low rate of infections with only light symptoms among kidney transplant patients treated with Evusheld®. A long-term study with a larger cohort might better evaluate the efficacy, outcomes and safety of this preexposure prophylaxis.

Frailty: A Strong Impact on Lung Transplant Outcomes?

Frailty: A Strong Impact on Lung Transplant Outcomes?

Continuation of immunosuppression vs. immunosuppression weaning in potential repeat kidney transplant candidates: a care management perspective.

Management of immunosuppression in patients with a failing or failed kidney transplant requires a complete assessment of their clinical condition. One of the major considerations in determining immunosuppression is whether or not such an individual is considered a candidate for re-transplantation. Withdrawal of immunosuppression in a re-transplant candidate can result in allosensitization and markedly reduce the chances of a repeat transplant. In this review, we summarize the effects of immunosuppression reduction on HLA sensitization, discuss the impacts of allosensitization in these patients, and explore reduction protocols and future directions. Risks of chronic immunosuppression, medical management of the failing allograft, and the effect of nephrectomy are covered elsewhere in this issue.

Incidence, landscape and survival outcome of de novo malignancy after double lung transplantation.

10574 Background: Organ transplant recipients are at greater risk of developing malignancies due to their immunosuppressive management. However, the incidence of post-transplant malignancy after double lung transplantation (DLT) has not been studied. This study investigated the incidence, trends, and most common types of post-transplant malignancy following DLT. Methods: Data extracted from the Organ Procurement Transplantation Network (OPTN) registry after DLT for non-cancerous disease. We evaluated the incidence of post-transplant malignancy, and assessed the annual and cumulative risk of each malignancy after DLT. And the overall survival (OS) of recipients with or without post-transplant malignancy was analyzed by Kaplan-Meire survival method. Results: A total of 23,935 cases were identified and analyzed from the OPTN database (13,768; 57.5% male, 10,167; 42.5% female). 5,629 cases (23.5%) were found to have post-transplant malignancy and 18,306 cases (76.5%) had no post-transplant malignancy. Among patients with post-transplant malignancy 3,785 (67.2%) were male and 1844 (32.8%) were female. Those with post-transplant malignancy had a longer OS compared to those without post-transplant malignancy (P &lt; 0.001). While the median OS was 97.2 months and 5-year survival rate was 83.6% in recipients with post-transplant malignancy, the median OS was 36.7 months and 5-year survival rate was 67.3% in For those without post-transplant malignancy. The risk for post-transplant malignancy was greatest during the first 3-5 years post-transplantation. The most common types of post-transplant malignancies were squamous cell skin cancer (n = 2711, 48.2%), basal cell skin cancer (n = 965, 17.1%), lymphoma (n = 570, 10.1%), lung cancer (n = 187, 3.3%), colorectal cancer (n = 184, 3.3%). Conclusions: The lifetime incidence of post-transplant malignancy following DLT was identified to be 20.1% and those with post-transplant malignancy had a longer OS compared to those without post-transplant malignancy. Further studies are needed to investigate the underlying mechanism for the increased risk of malignancy following DLT and its association with OS.

Understanding the Elevated Lethality of COVID-19 in Liver Transplant Recipients: Does Immunosuppression Management Matter? Results from a Brazilian Multicentric Historical Cohort

Infections by SARS-CoV-2 in liver transplant recipients (LT) patients are of particular concern, notably due to perceived added risks related to immunosuppression and comorbidity burden. Current literature on this topic often relies on small, non-standardized, and geographically limited studies. This manuscript describes COVID-19 presentations and causes for elevated mortality in a large cohort of LT recipients. This study was designed as a multicentric historical cohort, including LT recipient patients with COVID-19 in 25 study centers, with the primary endpoint being COVID-related death. We also collected demographic, clinical, and laboratory data regarding presentation and disease progression. Two hundred and thirty-four cases were included. The study population was predominantly male and White and had a median age of 60 years. The median time from transplantation was 2.6 years (IQR 1-6). Most patients had at least one comorbidity (189, 80.8%). Patient age (P=.04), dyspnea (P < .001), intensive care unit admission (P < .001), and mechanical ventilation (P < .001) were associated with increased mortality. Modifications of immunosuppressive therapy (P < .001), specifically the suspension of tacrolimus, maintained significance in multivariable analysis. Attention to risk factors and the individualization of patient care, especially regarding immunosuppression management, is crucial for delivering more precise interventions to these individuals.

Clinical Decision Support Systems Used in Transplantation: Are They Tools for Success or an Unnecessary Gadget? A Systematic Review

Although clinical decision support systems (CDSSs) have been used since the 1970s for a wide variety of clinical tasks including optimization of medication orders, improved documentation, and improved patient adherence, to date, no systematic reviews have been carried out to assess their utilization and efficacy in transplant medicine. The aim of this study is to systematically review studies that utilized a CDSS and assess impact on patient outcomes. A total of 48 articles were identified as meeting the author-derived inclusion criteria, including tools for posttransplant monitoring, pretransplant risk assessment, waiting list management, immunosuppressant management, and interpretation of histopathology. Studies included 15 984 transplant recipients. Tools aimed at helping with transplant patient immunosuppressant management were the most common (19 studies). Thirty-four studies (85%) found an overall clinical benefit following the implementation of a CDSS in clinical practice. Although there are limitations to the existing literature, current evidence suggests that implementing CDSS in transplant clinical settings may improve outcomes for patients. Limited evidence was found using more advanced technologies such as artificial intelligence in transplantation, and future studies should investigate the role of these emerging technologies.

New Perspectives in Cytomegalovirus After Transplant: The Role of Immunosuppressant Management.

New Perspectives in Cytomegalovirus After Transplant: The Role of Immunosuppressant Management.

Immunosuppressive therapy management in cancer patients with autoimmune diseases treated with immune checkpoint inhibitors: A case series and systematic literature review.

Prescribing immune checkpoint inhibitors (ICIs) to cancer patients with an autoimmune disease (AID) is presumed safe when cautious adverse event management is applied. However, guidelines on immunosuppressant (IS) adaptations are limited and real-world evidence is scarce. Current practice of IS adaptations is described in a case series of AID patients treated with ICIs in a tertiary university hospital in Belgium (1/1/2016-31/12/2021). Patient, drug and disease-related data were documented using retrospective chart review. A systematic search of the PubMed database was performed to identify similar cases (1/1/2010-30/11/2022). Sixteen patients were described in the case series (62% with active AID). Systemic IS were changed before ICI initiation in 5/9 patients. Four patients continued therapy, of which one achieved partial remission. Patients who had IS (partially) stopped before ICI start (n = 4) had AID flares in two cases; immune-related adverse events in three cases. In the systematic review, 37 cases were identified in 9 articles. Corticosteroids (n = 12) and non-selective IS (n = 27) were continued in, respectively, 66% and 68% of patients. Methotrexate was frequently discontinued (13/21). Biologicals, excluding tocilizumab and vedolizumab, were withheld during ICI treatment. Out of all patients with flares (n = 15), 47% had stopped IS therapy before ICI start and 53% had continued their AID drugs. A detailed overview of IS management in patients with AID receiving ICI therapy is presented. Expanding the knowledge base germane to IS management with ICI therapy in the diverse population is essential to evaluate their mutual impact, thus advancing responsible patient care.

High exposure to tacrolimus is associated with spontaneous remission of recurrent membranous nephropathy after kidney transplantation.

We aimed to characterize the incidence and clinical presentation of membranous nephropathy (MN) after kidney transplantation (KT), and to assess allograft outcomes according to proteinuria rates and immunosuppression management. Multicenter retrospective cohort study including patients from six Spanish centers who received a KT between 1991-2019. Demographic, clinical, and histological data were collected from recipients with biopsy-proven MN as primary kidney disease (n=71) or MN diagnosed de novo after KT (n=4). Up to 25.4% of patients with biopsy-proven MN as primary kidney disease recurred after a median time of 18.1 months posttransplant, without a clear impact on graft survival. Proteinuria at 3-months post-KT was a predictor for MN recurrence (rMN, HR 4.28; P=0.008). Patients who lost their grafts had higher proteinuria during follow-up [1.0 (0.5-2.5) vs 0.3 (0.1-0.5) g/24h], but only eGFR after recurrence treatment predicted poorer graft survival (eGFR<30ml/min: RR=6.8). We did not observe an association between maintenance immunosuppression and recurrence diagnosis. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence (trough concentration/dose ratio: 2.86vs 1.18; P=0.028). Up to 94.4% of KT recipients received one or several treatments after recurrence onset: 22.2% rituximab, 38.9% increased corticosteroid dose, and 66.7% ACEi/ARBs. Only 21 patients had proper antiPLA2R immunological monitoring. One-fourth of patients with biopsy-proven MN as primary kidney disease recurred after KT, without a clear impact on graft survival. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence.

Diagnosis, treatment protocols, and outcomes of liver transplant recipients infected with COVID-19.

Several cases of fatal pneumonia during November 2019 were linked initially to severe acute respiratory syndrome coronavirus 2, which the World Health Organization later designated as coronavirus disease 2019 (COVID-19). The World Health Organization declared COVID-19 as a pandemic on March 11, 2020. In the general population, COVID-19 severity can range from asymptomatic/mild symptoms to seriously ill. Its mortality rate could be as high as 49%. The Centers for Disease Control and Prevention have acknowledged that people with specific underlying medical conditions, among those who need immunosuppression after solid organ transplantation (SOT), are at an increased risk of developing severe illness from COVID-19. Liver transplantation is the second most prevalent SOT globally. Due to their immunosuppressed state, liver transplant (LT) recipients are more susceptible to serious infections. Therefore, comorbidities and prolonged immunosuppression among SOT recipients enhance the likelihood of severe COVID-19. It is crucial to comprehend the clinical picture, immunosuppressive management, prognosis, and prophylaxis of COVID-19 infection because it may pose a danger to transplant recipients. This review described the clinical and laboratory findings of COVID-19 in LT recipients and the risk factors for severe disease in this population group. In the following sections, we discussed current COVID-19 therapy choices, reviewed standard practice in modifying immunosuppressant regimens, and outlined the safety and efficacy of currently licensed drugs for inpatient and outpatient management. Additionally, we explored the clinical outcomes of COVID-19 in LT recipients and mentioned the efficacy and safety of vaccination use.