Maintenance Immunosuppressive Regimen Research Articles

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.

Assessing the cost-effectiveness of replacing antimetabolites with mTOR inhibitors in heart transplant immunosuppression in China: a network meta-analysis-based economic evaluation.

Although several pharmacoeconomic studies have assessed the cost-effectiveness of maintenance immunosuppressive regimens for heart transplant recipients, economic comparisons between various combination drug therapies remain sparse. This study used an economic evaluation based on network meta-analysis to assess the cost-effectiveness of four immunosuppressive regimens for adult heart transplant recipients in China. We conducted a systematic search for clinical trials in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP database. A validated Markov model was adapted to reflect the Chinese medical landscape. Four maintenance immunosuppression regimens were considered: tacrolimus/mycophenolate mofetil (TAC/MMF), cyclosporine/mycophenolate mofetil (CSA/MMF), everolimus/cyclosporine (EVL/CSA), and sirolimus/tacrolimus (SRL/TAC). The probabilities of health events were derived from a comprehensive literature review. Direct medical costs, adjusted for 2022 values, were from public documents and websites, while utilities for quality-adjusted life-years (QALYs) were taken from previous studies. Primary outcomes were mean lifetime cost, QALYs, and cost-effectiveness, with a willingness-to-pay (WTP) threshold set at three times China's GDP per capita in 2022. Sensitivity analyses were conducted to test the robustness of the results. The base case analysis identified TAC/MMF as the most cost-effective regimen, producing a mean of 6.31 QALYs per patient at a cost of Chinese Yuan (CNY) 534,182.89. Sensitivity analyses consistently reinforced TAC/MMF as the most cost-effective and robust choice. TAC/MMF is the most cost-effective maintenance immunosuppressive regimen for heart transplant recipients within the Chinese health system. The study findings are reinforced by sensitivity analyses, affirming their robustness amid various uncertainties.

P.135: Comparison between tacrolimus-based and cyclosporine-based maintenance immunosuppressive regimens in kidney transplant recipients with functioning grafts beyond 15 years.

P.135: Comparison between tacrolimus-based and cyclosporine-based maintenance immunosuppressive regimens in kidney transplant recipients with functioning grafts beyond 15 years.

P.134: Assessment of tacrolimus-based vs. cyclosporine-based maintenance immunosuppressive regimens among living donor kidney transplant recipients with low immunological risk: Single centre experience.

P.134: Assessment of tacrolimus-based vs. cyclosporine-based maintenance immunosuppressive regimens among living donor kidney transplant recipients with low immunological risk: Single centre experience.

Belatacept based immunosuppression: What and when to combine?

IntroductionThis study examines the effect of belatacept based salvage regimens on kidney transplant outcomes. MethodsThis single-center retrospective study included all adult kidney transplant recipients between 2011 and 2022 who were converted to belatacept salvage therapy during their follow up. eGFR, graft survival, incidence of infections and neoplasia, histology and DSA data were collected through systematic review of the medical record. ResultsPatients were divided into 3 groups based on salvage regimen: Mycophenolate mofetil/belatacept (MMF/Bela) (n = 28), low-dose Calcineurin inhibitors/belatacept (CNI/Bela) (n = 22), and low-dose Calcineurin inhibitors/ Mycophenolate mofetil /belatacept (CNI/MMF/Bela) (n = 13). Patients with antibody-mediated rejection were more likely to receive CNIs in addition to belatacept (low-dose CNI/MMF/Bela 54%, low-dose CNI/Bela 45%, MMF/Bela 3.6%, p < 0.001). DSA decreased in all groups after transition to belatacept by 15.67% (p = 0.15). No difference in Glomerular filtration rate (eGFR) over time was observed between the groups, and eGFR remained stable over the first year after transition to belatacept. The incidence of death and allograft failure was similar between the groups (low- dose CNI/MMF/Bela n = 3, low-dose CNI/Bela n = 7, MMF/Bela n = 4; p = 0.41). Patients in the low-dose CNI/Bela cohort who were transitioned to belatacept within 6 months from transplant showed a decline in eGFR over the first year after transition, while the other treatment cohorts demonstrated stable or slight increase in eGFR. ConclusionsThe present study demonstrates comparable transplant outcomes in terms of eGFR, graft survival, incidence of infections and neoplasia, rejection rate and donor specific antibody (DSA) in three belatacept-based maintenance immunosuppression regimens supporting the safety and efficacy of these therapeutic options.

Long-term outcomes of two-dose alemtuzumab induction in pediatric kidney transplantation.

Alemtuzumab is a lymphocyte depleting agent used for induction in kidney transplant, but long-term information on its use in pediatric recipients remains sparse. We performed a single-center retrospective cohort study of 57 pediatric kidney transplant recipients receiving alemtuzumab 20 mg/m2/dose ×2 doses for induction immunosuppression. All patients underwent surveillance biopsies, and 91.3% underwent steroid withdrawal by day 4 post-transplant. Outcomes of interest included graft survival, development of donor specific antibodies (DSA), incidence of viremia and PTLD, and duration of lymphopenia. Median follow-up time was 7.9 years (IQR 5-13.6 years). Median graft survival was 16.5 years (95% CI 11.6-unknown). DSA developed in 36.5% at a median of 944 days (IQR 252-2113 days). Incidences of BK polyomavirus DNAemia (BKPyV-DNAemia), CMV DNAemia, and EBV DNAemia were 38.6%, 22.8%, and 14%, respectively; one patient developed PTLD at 13.3 years post-transplant. Median duration of lymphopenia was 365 days (IQR 168-713 days); 19.3% of patients remained lymphopenic at 3 years post-transplant. There was no association between duration of lymphopenia and graft survival, rejection, DSA detection, or viremia. A two-dose alemtuzumab induction protocol can have excellent outcomes with a steroid-free maintenance immunosuppression regimen. More comprehensive, multicenter, comparative studies of pediatric kidney transplant are needed to improve long-term outcomes.

An update review of post-transplant diabetes mellitus: Concept, risk factors, clinical implications and management.

Kidney transplantation is the gold standard therapeutic alternative for patients with end-stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post-transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies. Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies. PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post-transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large-scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose-lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients. The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients.

Clinical outcomes of intestinal transplant recipients receiving maintenance basiliximab, sublingual tacrolimus and prednisone: A case series

IntroductionIntestinal transplantation poses a unique challenge in the field of solid organ transplantation. The combination of tacrolimus and prednisone stands as the foundational cornerstone of maintenance immunosuppression in the field of intestinal transplantation. This case series aims to describe 1–year clinical outcomes of 5 intestinal transplant recipients who received a novel immunosuppression regimen consisting of monthly basiliximab, sublingual tacrolimus, and prednisone. MethodsA retrospective analysis of patients who underwent intestinal transplantation in our center between January 01, 2020, and January 31, 2022, was conducted. Each recipient was followed for at least 1-year post-transplant. Recipient baseline demographics, clinical characteristics, and follow-up data were obtained from the electronic health records. Data collection included recipient demographics (age, sex, race/ethnicity, BMI), cause of intestinal failure, immunological data, infectiology data and treatment information. ResultsA total of five patients underwent intestinal transplantation, of which two males (40 %) and three females (60 %), with a median age of 20.1 years (17.4–28.8). The median (IQR) tacrolimus trough by month 1 was 10.4 (8.4–13.2) ng/mL. Subsequently, the median (IQR) tacrolimus troughs at specified periods are as follows, respectively: month 3: 10.2 (8.2–13.2) ng/mL; month 6: 8.4 (7.6–9.6) ng/mL; and month 12: 8.8 (6.2–9.8) ng/mL. Three patients (60.0 %) had biopsy proven rejection, but all of them had resolution after the optimization of immunosuppression. All patients were alive and had a functioning intestinal allograft at 1-year. ConclusionThe combination of monthly basiliximab, sublingual tacrolimus, and prednisone is an effective novel maintenance immunosuppression in intestinal transplantation. A larger and more extended study duration would be necessary to thoroughly assess the safety and sustained benefits of the novel maintenance immunosuppression regimen.

Successful management of concurrent COVID-19 and Pneumocystis Jirovecii Pneumonia in kidney transplant recipients: a case series

BackgroundPneumocystis pneumonia (PCP) is a life-threatening pulmonary fungal infection that predominantly affects immunocompromised individuals, including kidney transplant recipients. Recent years have witnessed a rising incidence of PCP in this vulnerable population, leading to graft loss and increased mortality. Immunosuppression, which is essential in transplant recipients, heightens susceptibility to viral and opportunistic infections, magnifying the clinical challenge. Concurrently, the global impact of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been profound. Kidney transplant recipients have faced severe outcomes when infected with SARS-CoV-2, often requiring intensive care. Co-infection with COVID-19 and PCP in this context represents a complex clinical scenario that requires precise management strategies, involving a delicate balance between immunosuppression and immune activation. Although there have been case reports on management of COVID-19 and PCP in kidney transplant recipients, guidance on how to tackle these infections when they occur concurrently remains limited.Case presentationsWe have encountered four kidney transplant recipients with concurrent COVID-19 and PCP infection. These patients received comprehensive treatment that included adjustment of their maintenance immunosuppressive regimen, anti-pneumocystis therapy, treatment for COVID-19 and other infections, and symptomatic and supportive care. After this multifaceted treatment strategy, all of these patients improved significantly and had favorable outcomes.ConclusionsWe have successfully managed four kidney transplant recipients co-infected with COVID-19 and PCP. While PCP is a known complication of immunosuppressive therapy, its incidence in patients with COVID-19 highlights the complexity of dual infections. Our findings suggest that tailored immunosuppressive regimens, coupled with antiviral and antimicrobial therapies, can lead to clinical improvement in such cases. Further research is needed to refine risk assessment and therapeutic strategies, which will ultimately enhance the care of this vulnerable population.

Effect of SARS-CoV-2 infection on anti-HLA antibodies and de novo donor specific antibodies incidence in lung transplant recipients

PurposeThere are no clear guidelines on how to handle immunosuppression in lung transplant recipients (LTRs) infected by SARS-CoV-2. Antimetabolite reduction with corticosteroid escalation is the most frequent strategy. The aim of this study was to determine the effect of this therapeutic approach on the incidence of de novo donor specific-antibodies (dnDSA). MethodsWe retrospectively analysed a cohort of 27 LTRs diagnosed with SARS-CoV-2 infection between September 2020 and April 2021 with available anti-HLA antibodies screening before and after infection. Managed as per the centre's SARS-CoV-2 protocol, the treatment modalities included specific virostatic treatment, convalescent plasma administration, reduction or discontinuation of mycophenolate and transient corticosteroid escalation initiated in the second week post-infection. ResultsAll 27 patients received virostatics: 15 (55.6%) remdesivir and 12 (44.4%) favipiravir. In addition, 18 patients (66.7%) underwent convalescent plasma therapy. Of the 27 patients, 25 (92.6%) received mycophenolate as a part of their maintenance immunosuppressive regimen, which was temporarily reduced in 10 (37%) and discontinued in 15 LTRs (55.6%), the median resumption times for mycophenolate daily doses of at least 1000 mg being 13 days (IQR 11.0–63.5) and 59 days (IQR 26.0–130.0), respectively. Corticosteroids were escalated in 25 patients (92.6%), of whom 9 (33.3%) received IV methylprednisolone (median 80 mg/day; IQR 80–187.5) and 16 (59.3%) had oral prednisone adjusted (median 20 mg/day; IQR 16.3–38.8). The median time to revert to the corticosteroid dosage of ≤20 mg/day was 42 days (IQR 36.0–87.0). Notably, no dnDSA were detected in any LTR between 1 and 9 months from the onset of the SARS-CoV-2 infection. ConclusionOur findings suggest that antimetabolite cessation with a transient corticosteroid escalation is a safe therapeutic strategy regarding anti-HLA dynamics in SARS-CoV-2 infected LTRs.

Early occurrence of acute myelomonocytic leukemia (M4/M5) after liver transplantation: a case report

IntroductionAcute myeloid leukemia is a rare event in post-liver-transplantation recipients. In the present report, we described a case of extramedullary acute myeloid leukemia, M4/M5 subtype, following orthotopic liver transplant.Case presentationThe patient was a 50-year-old Iranian woman who underwent orthotopic liver transplant due to hepatitis B-related cirrhosis (Child C, MELD (model for end-stage liver disease score) = 22). Orthotopic liver transplant was performed using the piggy back technique in January 2022. Induction immunosuppressive therapy was 1 gm methylprednisolone for 3 days followed by a triple maintenance immunosuppressive regimen including mycophenolate mofetil, prednisolone, and tacrolimus. About 5 months after orthotopic liver transplant in June 2022, the patient presented with leukocytosis, with white blood cell count of 99.4 × 103/µl, and physical examination revealed only cervical lymphadenopathy. Biopsy of cervical lymph nodes showed a myeloid tumor. She was immediately hospitalized. Eight hours after hospitalization, the patient gradually developed lethargy and decreased O2 saturation to approximately 89%. Flow cytometry demonstrated the markers of a myelomonocytic acute myeloid leukemia (M4/M5). Cytoreduction was immediately started by intensive leukopheresis followed by induction therapy. Because of a septic complication during the induction therapy, further chemotherapy was discontinued and broad-spectrum antibiotics and antifungal treatments started. Unfortunately, our patient died of severe septic shock 42 days after hospitalization.ConclusionAcute myeloid leukemia is a rare phenomenon after liver transplantation, and it can follow a rapidly fatal clinical course.

Current approaches in managing pregnancy in kidney transplant recipients

End-stage renal disease impacts fertility, causing functional menopause in female patients. Within 3 months of successful renal transplant, menstrual function normalizes, ovulation recommences due to improved hypothalamic–pituitary–ovarian axis function, and, thereby, fertility is restored in 80–90% of women in the childbearing age group. In such circumstances, any unplanned pregnancy poses a significant risk to the mother and the child, and the allograft. Pregnancy, in general, does not negatively impact long-term allograft function or survival if the baseline function of the allograft is excellent. Risk predictors of clinical adverse outcomes and graft loss during pregnancy include short transplant–pregnancy interval, preconception graft function, hypertension, preconception proteinuria, and preeclampsia. The recommended and safer maintenance immunosuppressive regimen during pregnancy is calcineurin inhibitors (CNI) (tacrolimus/cyclosporine), azathioprine, and steroids. Sirolimus/everolimus and mycophenolate mofetil should be withdrawn 6 weeks before planned conception. To avoid acute rejections, drug levels should be monitored closely, and the dosage should be modified to reach the recommended target level. Addressing contraception must be a crucial component of the pretransplant counseling process to prevent premature unplanned pregnancies. Mechanical contraceptives are safe for transplant recipients, convenient, and easy to use, with no concerns regarding interaction with immune suppressants; nevertheless, their efficacy depends on user compliance which is difficult to achieve in most cases. However, combined oral contraceptives and progestin-only contraceptives have an inhibitory effect on P 450 3A4, thus increasing the concentration of CNIs particularly cyclosporine. Furthermore, CNIs, in particular, tacrolimus, have an inductive effect on P 450 3A4, potentially reducing the contraceptive efficacy. Therefore, successful pregnancy depends on thorough prepregnancy counseling, careful family planning, and multidisciplinary teamwork. Breastfeeding is not contraindicated and should not be discouraged.

BI29 Crusted scabies: a complicated course in a renal transplant recipient

Abstract A 55-year-old man of Nigerian origin was admitted with a 3-month history of a generalized rash that was intensely pruritic at night. He had received a renal transplant 1 year prior for end-stage kidney disease in the context of hypertensive nephropathy. His maintenance immunosuppressive regimen includes mycophenolate mofetil, tacrolimus and prednisolone. No household contacts were affected by itch. He had been treated with the topical scabicide permethrin cream in the community, resulting in a painful fissuring of the lower limbs that prompted presentation to the emergency department. Full skin examination revealed an extensive scaling eruption, with profuse skin shedding and lichenified fissuring of the lower limbs. There were also loosely adherent, grey, hyperkeratotic scaling plaques widely extending from the genitals to mid-thigh and posterior upper limbs, with involvement of the ear lobes. There was relative sparing of the acral areas. He was initially treated empirically with oral ivermectin, oral flucloxacillin and topical clobetasol propionate ointment and paraffin gel. A full blood count revealed a prominent eosinophilia. A punch biopsy later revealed a number of scabies mites. He was prescribed ivermectin as per the Centers for Disease Control guidelines for crusted scabies in immunosuppressed populations with oral ivermectin 200 μg kg–1 on days 1, 2, 8, 9, 15, 22 and 29. Supply issues in the community delayed his treatment course. Further topical antiscabietic therapy was deferred until tolerated. He was subsequently re-admitted with methicillin-sensitive Staphylococcus aureus bacteraemia with pyelonephritis of the transplant kidney. The prescribed treatment regime of oral ivermectin, a topical keratolytic cream and topical permethrin cream daily for 7 days was completed as an inpatient. This yielded complete resolution of his crusted lesions. He responded well to a prolonged course of intravenous flucloxacillin. This case illustrates the challenge of diagnosing scabies in richly pigmented skin, as well in the immunosuppressed host (in this case due to defective T-cell responses). Maintaining a high index of suspicion is essential in the context of unexplained itch in the immunosuppressed as they may present with atypical presentations. Such vigilance will improve the recognition and management of this uncommon, potentially life-threatening infectious complication of crusted scabies in the transplant population (Wang MK, Chin-Yee B, Lo CKL et al. Crusted scabies in a renal transplant recipient treated with daily ivermectin: a case report and literature review. Transpl Infect Dis 2019; 21:e13077).

Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines.

Kidney transplant recipients (KTRs) commonly suffer from impaired immunity. KTRs' compromised immune response to COVID-19 vaccines indicates urgent revision of immunisation policies. A cross-sectional study was conducted in Madinah, Saudi Arabia of 84 KTRs who had received at least one dose of a COVID-19 vaccine. ELISA was used to evaluate anti-spike SARS-CoV-2 IgG and IgM antibody levels in blood samples obtained one month and seven months after vaccination. Univariate and multivariate analyses were performed to identify associations between seropositive status and factors such as the number of vaccine doses, transplant age, and immunosuppressive therapies. The mean age of KTRs was 44.3 ± 14.7 years. The IgG antibody seropositivity rate (n=66, 78.5%) was significantly higher than the seronegativity rate (n=18, 21.4%) in the whole cohort (p<0.001). In KTRs seroconverting after one month (n=66), anti-SARS-CoV-2 IgG levels declined significantly between one month (median [IQR]:3 [3-3]) and seven months (2.4 [1.7-2.6]) after vaccination (p<0.01). In KTRs with hypertension, IgG levels significantly decreased between one and seven months after vaccination (p<0.01). IgG levels also decreased significantly in KTRs with a transplant of >10 years (p=0.02). Maintenance immunosuppressive regimens (triple immunosuppressive therapy and steroid-based and antimetabolite-based regimens) led to a significant decrease in IgG levels between the first and second sample (p<0.01). KTRs receiving three vaccine doses showed higher antibody levels than those receiving a single dose or two doses, but the levels decreased significantly between one (median [IQR]: 3 [3-3]) and seven months (2.4 [1.9-2.6]) after vaccination (p<0.01). KTRs' humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of >10 years.

Outcomes in kidney transplant recipients treated with immediate-release tacrolimus capsules versus extended-release tacrolimus capsules: A cohort study.

Prior randomized trials and observational studies have generally reported similar outcomes in kidney transplant recipients (KTRs) treated with immediate-release tacrolimus (IR-TAC) versus extended-release tacrolimus (ER-TAC). However, many of these previous studies focused on patients with low immunological risks, had small sample sizes and brief follow-up periods, and excluded outcomes associated with graft loss, such as chronic rejection. To address these limitations, we conducted a cohort study of 848 KTRs at a single transplantation center who had generally high immunological risks and were treated with either IR-TAC capsules (589 patients, 65.9%) or ER-TAC capsules (289 patients, 34.1%). All patients received their designated maintenance immunosuppressive regimen for at least 3months post-transplantation. Afterwards, tacrolimus formulation was at the discretion of each patient's transplant nephrologist. For the two treatment groups, we compared the hazards of experiencing a composite outcome of acute or chronic antibody-mediated rejection (AMR), acute or chronic T-cell-mediated rejection, de novo DSA, and/or graft loss over a 3-year period starting at 3 months post-transplantation. In a multivariable Cox proportional hazards regression model, KTRs treated with IR-TAC capsules had an increased hazard of experiencing the composite outcome when compared to patients treated with ER-TAC capsules; however, this result was not significant (adj HR 1.24, 95% CI .92-1.68, p=.163). Similar results were obtained with inverse probability of treatment weighting (IPTW) using a propensity score (adj HR 1.25, 95% CI .93-1.68, p=.146). These findings suggest that when compared to IR-TAC capsules, ER-TAC capsules do not reduce the hazard of poor outcomes in KTRs with generally high immunological risks.

Conversion to Belatacept in kidney transplant recipients with chronic antibody-mediated rejection (CAMR)

BackgroundThe costimulatory inhibitor Belatacept (Bela) has been shown to be an effective alternative in several clinical situations, including chronic antibody-mediated rejection, calcineurin toxicity, and de novo alloantibody formation. To further explore the usefulness of Belatacept under various clinical scenarios, we performed a retrospective analysis of a prospective database of all recipients who had a BPAR diagnosis of CAMR and were converted to a Belatacept maintenance immunosuppression regimen after kidney transplantation. Material and methodWe conducted a retrospective analysis of a prospectively collected database of all kidney transplants adult patients at SUNY Upstate Medical Hospital from 1 January 2013 to 31 December 2021. Our inclusion criteria were the patients who have been diagnosed with CAMR according to their renal biopsy based on the 2013 Banff criteria. The primary objective was to compare the kidney viability and function using GFR between the two interest groups and finally compare the outcomes. ResultsA total of 48 patients met our inclusion criteria based on the kidney biopsy result, which showed chronic antibody-mediated graft rejection (CAMR). Nineteen patients (39.6%) were converted to the Belatacept, and we continued the previous immunosuppression regimen in 29 patients (60.4%). The mean time from the transplant date to the diagnosis of CAMR was 1385 days in the Belatacept group and 914 days for the non-Belatacept group (P = 0.15). The mean GFR comparison at each time point between the groups did not show a significant difference, and Belatacept did not show superiority compared to the standard immunosuppression regimen in terms of kidney function preservation. 1 (5.2%) patient from the Belatacept group and 1 (3.4%) patient from the non-Belatacept group had a biopsy-proven acute rejection (BPAR) after CAMR confirmation, and it was comparable (P = 0.76). De novo synthesis of the DSA rate was 12.5% in the Belatacept group and 15% In the non-Belatacept group, which was comparable. (P = 0.90). The patient survival rate was 100% in both groups. ConclusionsWe conclude that compared to the standard Tacrolimus/MMF/Prednisone regimen, Belatacept did not significantly benefit in preserving the GFR in long-term follow-ups and stabilizing the DSA production, which is one of the main factors resulting in chronic graft failure.

Humoral Response After SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Role of Immunosuppression Therapy

BackgroundMessenger RNA vaccination against COVID-19 has been shown to produce an immune response with sufficient efficacy to prevent natural infection in immunocompetent recipients. However, the response in kidney transplant recipients is low. We aimed to evaluate the specific humoral response to SARS-CoV-2 after vaccination in a population of kidney transplant recipients and assess the main factors associated with a lack of response.MethodsWe undertook a prospective study of 105 kidney transplant recipients and 11 recipients of a combined kidney-pancreas transplant. We analyzed immunoglobulin G and immunoglobulin M antibodies after the patients received their second and third doses of the messenger RNA 1273 (Moderna) or BNT162b1 (BionTECH-Pfizer) vaccinations between February and November 2021.ResultsMean (SD) age of the 116 patients was 50 (16) years, and 65% were men. They had their transplants for 40 months (IQR, 15-123 months), with 14% undergoing retransplant and 11% sensitized. The maintenance immunosuppression regimen was steroids + tacrolimus + mycophenolate (MMF) in 68% of the patients and any combination with mammalian target of rapamycin inhibitor (mTORi) in 28%. A humoral response developed in 40% of the patients 6 weeks (IQR, 4-10 weeks) after receiving the second dose of the vaccine. Of the 67 patients with no response to the second dose, 51 had an analysis of the humoral response after the third dose, which was positive in 16 (31%). A total of 80% received the Moderna vaccine and 20% the BionTECH-Pfizer. No patient experienced major adverse effects after the vaccination.Factors associated with a lack of humoral response to the vaccine were recipient age (odds ratio [OR], 1.02; 95% CI, 1.001-1.05; P = .04), diabetes (OR, 2.8; 95% CI, 1.2-6.9; P = .02), and treatment with MMF (OR, 2.6; 95% CI, 1.08-6.8; P = .03). Treatment with mTORi was associated with a better response to vaccination (OR, 0.3; 95% CI, 0.1-0.9; P = .04).ConclusionsThe humoral response to the COVID-19 vaccine in kidney transplant recipients is poor. Factors related with this lack of immunity are recipient age and diabetes, plus MMF therapy, whereas mTORi therapy was associated with a better response to vaccination.

COVID-19 IN LUNG TRANSPLANT RECIPIENTS: A SINGLE CENTER EXPERIENCE

COVID-19 IN LUNG TRANSPLANT RECIPIENTS: A SINGLE CENTER EXPERIENCE

Impact of DSA and immunosuppression minimization on rejection, graft, and patient survival after simultaneous liver-kidney transplantation.

BackgroundAcute rejection rate is low after simultaneous liver–kidney transplantation (SLKT), leading some groups to minimize immunosuppressive (IS) regimens. However, the impact of preformed (pDSA) or de novo donor-specific antibodies (dnDSA) on the graft remains unclear.MethodsWe performed a retrospective analysis of 102 consecutive SLKT patients to study the impact of anti-HLA antibodies.ResultsAnti-HLA antibodies were detected in 75 recipients (class I 23.8%, both classes I and II 23.8%, and class II 14.3%). In total, 42.8% of the patients had pDSA and 21.7% developed dnDSA. Overall patient survival at 1–3 and 5 years, was respectively 88, 84, and 80%. Acute rejection occurred respectively in 3 (2.9%) liver and 6 kidney (5.9%) recipients. pDSA with titers over 10,000 mean fluorescence intensity (14.3%) was associated with lower patient survival (40 vs. 82%) but not with acute rejection. In a multivariable Cox regression analysis, the risk of death was associated with maleness, the highest titer of pDSA (p < 0.0007) or the sum of pDSA >10,000. Renal function did not differ between patients with class I pDSA (p = 0.631) and those with class II pDSA (p = 0.112) or between patients with and without a positive cross-match (p = 0.842). dnDSA were not associated with acute rejection, graft dysfunction or patient survival. IS minimization was not associated with rejection, graft dysfunction or death.ConclusionIn SLKT, high levels of pDSA >10,000 were associated with lower patient survival, but not rejection or graft survival. Minimization of maintenance immunosuppression regimen was not associated with a poorer outcome.

Association Between Maintenance Immunosuppressive Regimens and COVID-19 Mortality in Kidney Transplant Recipients.

Background.Solid organ transplant recipients are at high risk for fatal forms of coronavirus disease 2019 (COVID-19). We conducted a cohort study among kidney transplant (KT) recipients from the French Solid Organ Transplant COVID-19 Registry to investigate the association between maintenance immunosuppressive drugs and 60-d mortality.Methods.Data from all KT recipients with COVID-19 included in the French Solid Organ Transplant COVID-19 Registry between February 28, 2020, and December 30, 2020, were retrieved. We evaluated associations between immunosuppressive drugs and death within 60 d using logistic regression, with all baseline characteristics considered to influence outcome or immunosuppressive regimen. The Benjamini-Hochberg correction was used for controlling false positive rate; 40 multiple imputations were performed. Adjusted P value <0.05 was considered statistically significant.Results.There were 1451 KT recipients included. Median age was 58 y, and 66.4% were men. Most frequent comorbidities were hypertension (81.9%), diabetes (34.5%), and cardiovascular disease (29.5%). Median time since transplant was 71 mo. Maintenance immunosuppression regimens included calcineurin inhibitors (1295, 89.2%), antimetabolites (1205, 83%), corticosteroids (1094, 75.4%), mammalian target of rapamycin inhibitors (144, 9.9%), and belatacept (58, 4.0%). Among 1451 transplant recipients, 201 (13.9%) died within 60 d. Older age and higher baseline serum creatinine were associated with mortality (odds ratios, 1.09 [1.07-1.11] and 1.01 [1.005-1.009], P < 0.001). Corticosteroid-free regimens were associated with a significantly lower risk of death (odds ratio, 0.48 [0.31-0.76]; P = 0.011).Conclusions.Corticosteroid-free regimens were associated with a lower risk of death in KT recipients with COVID-19. Long-term exposure to corticosteroids impairs immune functions and may predispose solid organ transplant recipients to severe forms of COVID-19.