Maintenance Immunosuppressive Therapy Research Articles

Hypothalamic-Pituitary-Adrenal Axis Activity and Metabolic Disorders in Kidney Transplant Recipients on Long-Term Glucocorticoid Therapy

Background/Objectives: Glucocorticoids are commonly used for maintenance immunosuppressive therapy in kidney transplant recipients (KTRs). We aimed to investigate the prevalence of hypothalamic-pituitary-adrenal (HPA) axis suppression and its association with metabolic disorders in stable KTRs on low-dose glucocorticoids. Methods: This cross-sectional study included adult KTRs on low-dose glucocorticoids. HPA axis suppression was defined as baseline morning cortisol < 5 μg/dL. Adrenocorticotropic hormone (ACTH), dehydroepiandrosterone-sulphate (DHEAS) and 24 h urinary free cortisol (UFC) levels were also assessed. Examined metabolic disorders included hypertension, dyslipidemia, central obesity and post-transplant diabetes mellitus (PTDM). Results: Eighty adult KTRs with a median 57 months (IQR 24–102) since transplantation were included in the study. The mean prednisolone dose was 5.0 ± 1.3 mg/day. Baseline cortisol < 5.0 μg/dL was observed in 27.5% of the KTRs. Participants with baseline cortisol < 5.0 μg/dL were older (55.1 vs. 47.4 years, p = 0.023) and had had a transplant for a longer time (101.4 vs. 67.0 months, p = 0.043), compared with the rest of the cohort. Baseline cortisol correlated positively with ACTH (rho = 0.544, p < 0.001), DHEAS (rho:0.459, p < 0.001) and UFC (rho: 0.377, p = 0.002). The area under the receiver-operating characteristic curve for ACTH as a predictor of baseline cortisol > 5.0 μg/dL was 0.79 [95% confidence interval (CI): 0.68–0.89]. After adjustment for covariates, HPA axis suppression was not associated with the examined metabolic disorders. Conclusions: Our study showed that stable KTRs on chronic low-dose glucocorticoids exhibited an increased prevalence of HPA axis suppression. ACTH may serve as a surrogate biomarker for HPA axis activity in this population. Further research could evaluate the association of glucocorticoid-induced HPA axis inhibition with metabolic disorders.

Inflammatory Optic Neuropathy

Optic neuritis is the primary inflammation of the optic nerve. Chronic Recurrent Isolated Optic Neuropathy is an inflammatory optic neuropathy characterized by its recurrent and/or chronic nature, as well as corticosteroid sensitivity. Relapses that occur after the reduction or cessation of steroids and more severe visual loss compared to demyelinating optic neuritis are characteristic features. Although patients initially tend to respond well to steroids, cumulative damage can lead to poor visual outcomes and permanent loss of the retinal nerve fiber layer and ganglion cell layer. Diagnosing inflammatory optic neuropathies is crucial, as maintenance immunosuppressive therapy should be initiated in patients with relapses to protect against permanent vision loss in many types.

Silent Hearing Loss in Kidney Transplant Patients Receiving Tacrolimus: A Fact or a Myth?

Background: It has been claimed that tacrolimus may have harmful effects on the auditory system, where it has been linked to ototoxicity and sensorineural hearing loss (SNHL). We evaluated silent SNHL in kidney transplant recipients (KTRs) receiving tacrolimus and the different factors affecting it compared to healthy controls. Materials and Methods: In this case control study, hearing functions were studied in 42 KTRs receiving tacrolimus as maintenance immunosuppressive therapy for more than 3 months in comparison to 27 age- and gender-matched healthy subjects using tympanometry, pure-tone audiometry (PTA), extended high frequency audiometry (EHFA), and transient evoked oto-acoustic emissions (TEOAEs). Also, different factors were studied in relation to SNHL. Results: PTA showed that 23.8%, 21.4%, and 4.8% had mild, moderate, and severe SNHL, respectively. One-fifth of KTRs had severe SNHL, according to EHFA. According to TEOAEs, 28.6% of KTRs had abnormal hearing. There was a significant positive correlation between the tacrolimus trough levels and the results of both the PTA (P = 0.002) and EHFA (P = 0.035) tests. Conclusion: SNHL was detected in about half of the studied KTRs. Silent SNHL in KTRs might be associated with higher tacrolimus trough levels.

Torquetenovirus Viremia Quantification Using Real-Time PCR Developed on a Fully Automated, Random-Access Platform.

Quantification of Torquetenovirus (TTV) viremia is becoming important for evaluating the status of the immune system in solid organ transplant recipients, monitoring the appearance of post-transplant complications, and controlling the efficacy of maintenance immunosuppressive therapy. Thus, diagnostic approaches able to scale up TTV quantification are needed. Here, we report on the development and validation of a real-time PCR assay for TTV quantification on the Hologic Panther Fusion® System by utilizing its open-access channel. The manual real-time PCR previously developed in our laboratories was optimized to detect TTV DNA on the Hologic Panther Fusion® System. The assay was validated using clinical samples. The automated TTV assay has a limit of detection of 1.6 log copies per ml of serum. Using 112 samples previously tested via manual real-time PCR, the concordance in TTV detection was 93% between the assays. When the TTV levels were compared, the overall agreement between the methods, as assessed using Passing-Bablok linear regression and Bland-Altman analyses, was excellent. In summary, we validated a highly sensitive and accurate method for the diagnostic use of TTV quantification on a fully automated Hologic Panther Fusion® System. This will greatly improve the turnaround time for TTV testing and better support the laboratory diagnosis of this new viral biomarker.

Recurrence of autoimmune liver diseases after liver transplantation: Review and expert opinion statement.

Autoimmune liver diseases (AILDs) constitute the fourth most common indication for liver transplantation (LT) across the world. In general, the outcomes after LT are acceptable; however, disease recurrence after LT is common for all AILD, which can negatively affect graft and overall survival. Several questions persist, including the risk factors associated with recurrent disease, optimal antirejection medications, strategies to reduce the risk of recurrence, and how to best incorporate these strategies into clinical practice. For that reason, we assembled an international group of experts to review evidence to address these outstanding questions regarding LT for AILD. Survival rates after LT are ~90% and 70% at 1 and 5 years, and recurrent disease occurs in 10%-50% of patients with AILD. In patients with disease recurrence, graft survival decreased by 18% and 28% and overall survival by 8% and 12% at 5 and 10 years after LT, respectively. Recurrent autoimmune hepatitis is associated with high aminotransferases and immunoglobulin G (IgG) before LT, lymphoplasmacytic infiltrates in the explants, and may be associated with the absence of steroids after LT. However, the efficiency and safety of triple immunosuppressive maintenance therapy is still debatable. Younger age at diagnosis with primary biliary cholangitis or LT is associated with primary biliary cholangitis recurrence. Preventive use of ursodeoxycholic acid reduces the risk of recurrence and has a benefit in graft and patient survival. Episodes of systemic inflammation, including T-cell-mediated rejection, active ulcerative colitis, and episodes of cholangitis, are associated with recurrent PSC. Recurrent disease for AILD is associated with worse graft and patient survival. Patients with autoimmune hepatitis could be considered for long-term low-dose predniso(lo)ne, whereas patients with primary biliary cholangitis should be placed on preventive ursodeoxycholic acid after LT. There are no specific treatments for PSC recurrence; however, adequate control of inflammatory bowel disease and optimal immunosuppression to avoid T-cell-mediated rejection should be encouraged.

#1286 Utility of cinacalcet treatment in kidney transplant recipients with persistent hyperparathyroidism

Abstract Background and Aims Secondary hyperparathyroidism occurs in the majority of patients with chronic kidney disease (CKD). It may persist in up to 50-66% of patients despite the initial decrease in PTH levels after successful kidney transplantation (KT). Maintaining parathyroid hormone (PTH) levels within the normal range during the post-transplant period is crucial because it is related to hypercalcemia, hypophosphatemia, and reduced bone mass in KT recipients. Studies have already demonstrated that persistent hyperparathyroidism is associated with graft loss and all-cause mortality. Vitamin D, vitamin D analogs, and calcimimetics are most commonly used to manage hyperparathyroidism. However, studies about the long-term effect of calcimimetic therapy on the allograft are still limited. In this study, we aim to investigate the long-term allograft results of patients who received cinacalcet treatment for hyperparathyroidism. Method This study was conducted in Gazi University nephrology dialysis and transplantation unit with 312 patients who were transplanted between 1996 and 2019 and continued routine follow-up visits. Persistent hyperparathyroidism is defined as elevated PTH levels after the first year of KT (serum PTH>88 pg/mL). All patients without concurrent hypercalcemia were treated with vitamin D or analogs according to their vitamin D levels. Patients with non-functional allograft and parathyroidectomy after KT were excluded from this study. In addition, patients with rejection episodes, which could be confounding factor for allograft survival, were excluded to evaluate the isolated effect of cinacalcet on the allograft function. We identified 115 patients with persistent hyperparathyroidism, of whom were treated with cinacalcet (n = 21) or not (n = 94). We analyzed the baseline characteristics, comorbidities, and immunosuppressive treatments of the groups. Additionally, annual eGFR changes (Δ eGFR) calculated based on baseline (post-transplantation 6th month) eGFR after KT was also examined to evaluate the effect of cinacalcet on the graft. Results The mean age of the patients was 44.3 ± 12.6 years, and 47 (41%) were women. The median follow-up time of the patients was 87 (49-117) months. Twenty-nine patients (25%) underwent cadaveric transplantation, and 47 (41%) patients received anti-thymoglobulin (ATG) in induction therapy. While all patients were given glucocorticoids as maintenance immunosuppressive therapy, 93 (81%) of the patients received tacrolimus and, 9 (8%) cyclosporin as CNI, 78 (68%) received anti-metabolite therapy. Fifty-eight patients (19%) were used mTORi. A total of 21 patients with persistent hyperparathyroidism (21%) were treated with cinacalcet. Dialysis time is longer in the cinacalcet-treated group than in the patients not treated with cinacalcet (p < 0.001). The preemptive transplantation rate was lower (p = 0.03), and the delayed graft function was higher in the cinacalcet-treated group (p = 0.04). In the first year after KT, serum median PTH levels were 227 (167-341) pg/ml in the cinacalcet group and 110 (86-160) pg/ml in the other group, respectively (<0.001). Also, serum phosphate level is lower in the treatment group (2.7 ± 0.4 mg/dl vs. 3.1 ± 0.7 mg/dl, p = 0.03). At the last visit of patients, we observed similar median PTH levels between groups [141 (100-222) vs. 108 (73-159), p = 0.08]. During the follow-up, CMV episodes and BKV nephropathy diagnosis rates were similar between the groups (Table 1). Δ eGFRs in the first year (p = 0.7), second year (p = 0.2), third year (p = 0.4), and fifth year (p = 0.6) after KT were similar between both groups. Conclusion Our study suggests that cinacalcet treatment could be a safe and effective treatment for patients with persistent hyperparathyroidism. In long-term follow-up, there is no evidence of a reduction of kidney function. However, more trials are still required for other clinical outcomes such as fracture risk and cardiovascular morbidity and mortality.

#1774 ANCA vasculitis with renal involvement: age as a prognostic factor

Abstract Background and Aims Older patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) commonly experience renal impairment and poor prognosis. The European Vasculitis Study Group trials showed that approximately 16.7% and 22.5% of older patients with AAV suffered from end-stage renal disease (ESRD) in 5- and 10-year durations. The aim of this study was to analyze differences in course and outcome of patients with AAV with respect to age. Method This retrospective observational study included patients with diagnosis of AAV and biopsy proven renal involvement between 2000-2021. Patients were divided into two groups according to age: ≥65 or <65 years old. We recorded baseline characteristics and clinical data during follow-up. Response was defined as a BVAS reduction of at least 50% or BVAS of 0, while receiving prednisone dose higher than 4 mg; and remission as BVAS of 0 while receiving prednisone dose of 4 mg or less. Results We included 42 patients with AAV diagnosis, 47.6% of which were 65 years-old or older. Mean age of the older age group was 77 ± 8 years. No differences were found between older and younger patients at baseline (BVAS, FFS extra-renal symptoms, serum creatinine at diagnosis, hematuria), Patients > 65 years were significantly more likely to present p-ANCA positive MPA, as shown in Table 1. There was no difference in initial or maintenance immunosuppressive therapy between the two groups. No differences were found between older and younger patients with regard to treatment response. Although we found no statistical differences, older patients had worse renal outcomes. The older adult group had a higher mortality rate, p 0.01. The average time to death was 27 months for patients over 65 years and 34.5 in those who were younger (p 0.71). Conclusion No differences were found between older and younger patients with regard to treatment response. However, mortality was higher during follow-up in the group of older patients. Our results suggest that more attention should be paid to older patients with severe renal impairment.

#2149 Kidney transplantation outcomes in lupus nephritis

Abstract Background and Aims Kidney transplantation (KT) is the renal replacement therapy of choice in patients with lupus nephritis (LN) who progress to end-stage renal disease (ESRD). The latest Spanish guidelines recommend the use of hydroxychloroquine after KT in these patients. Our study aims to analyze KT outcomes in patients with LN in our center. Method Retrospective cohort study, which included all KT with a diagnosis of LN who underwent KT between April 1982 and November 2023 at Puerta del Mar University Hospital (Spain). Each KT recipient with LN was matched with two controls from the same institution by age, sex and type of donor during the same period. We collected clinical and demographical characteristics, as well as immunosuppressive (IS) therapy after KT. We analyzed the death-censored graft survival and patient survival and compiled the causes of death and graft loss, comparing them with the control group. We documented LN recurrences, KT rejections, and incidence of CMV and BK infection. Results In this period, 2055 KTs were performed in our center, of which 39 had a diagnosis of LN (1.9%). Seventy eight controls were selected. The majority of KTs were women (89.7%) with a mean age of 44 years. Induction therapy was used in 85.2% of KT with Thymoglobulin (63%) or Basiliximab (27%). Maintenance IS therapy was based on tacrolimus (93.5%), cyclosporine (6.5%), mycophenolate (100%) and prednisone (100%). Only 4 patients (10.2%), the latest ones, received hydroxychloroquine after KT. Death-censored graft survival at 1 year (87.1% SLE vs. 88.5% Non-SLE), 5 years (74.9% SLE vs. 80.8% Non-SLE), and 10 years (65.6% SLE vs. 69.5% Non-SLE) and patient survival at 1 year (97.1% SLE vs. 100% Non-SLE), 5 years (93.7% SLE vs. 95.3% Non-SLE), and 10 years (93.7% SLE vs. 91.7% Non-SLE) were similar in both groups. No graft was lost because of recurrent LN. No significant differences were found neither in the causes of death nor between the causes of graft loss. The incidence of CMV and BK infection and KT rejection rates were similar in both groups. Conclusion KT is an excellent therapeutic alternative in LN with ESRD. Despite the low use of hydroxychloroquine in our series, no recurrence of LN was detected and the KT outcomes were similar to the control group.

Anti-N-methyl-D-aspartate Receptor Encephalitis in People Living with HIV: Case Report and Literature Review.

With the increase in the number of cases of autoimmune encephalitis (AE), the cerebrospinal fluid (CSF) of people living with HIV (PLWH) showing abnormal behavior, cognitive impairment or abnormal movements should be actively screened for the antibody panel of AE. Early recognition and treatment can prevent severe seizures or coma and markedly improve the prognosis of patients. The first-line immunotherapy for AE includes intravenous methylprednisolone and immunoglobulin. However, whether long-time immunosuppressive maintenance therapy is needed is debated. For PLWH, immunosuppressive therapy and even steroids could be more challenging. Here, we review and summarize the clinical characteristics often reported cases and report one case from our center to improve the diagnosis and treatment of anti-N-methyl-D-aspartate receptor encephalitis in PLWH.

Medical Maintenance Therapy Following Laser Excision in Patients With Granulomatosis With Polyangiitis (GPA)-Associated Subglottic Stenosis.

To report on a series of patients with cANCA/PR3-positive, granulomatosis with polyangiitis (GPA)-associated subglottic stenosis (SGS) and evaluate response to medical maintenance therapy with rituximab versus other immunosuppressants following initial endoscopic laser excision. Retrospective chart review. Tertiary academic center. A retrospective chart review of patients with SGS and cANCA/PR3-positive GPA who received immunosuppressive maintenance therapy following endoscopic laser excision at our institution from June 1989 to March 2020 was performed. Data pertaining to patient demographics, clinical features, medications, and endoscopic laser procedures were collected. A total of 27 patients (15 women) with mean age (range) of 40 (19-59) years and mean (range) follow-up of 12.6 years (1.5-28.6) were identified. Sixteenpatients (60%) had limited GPA. Six patients (24%) had previously received local intervention with open surgery (n = 1, 4%) or endoscopic techniques (n = 5, 20%). All patients experienced symptom improvement following initial CO2 laser excision at our institution without any procedural complications or adverse events. Following initial laser excision, 15 patients (60%) were treated with rituximab and 10 patients (40%) were treated with nonrituximab immunosuppressive agents. Patients treated with rituximab were less likely to recur (P = 0.040). Limited GPA was associated with an increased incidence of recurrence (P = 0.031). Median time (years) to recurrence (range) was 3.2 (0.3-19.3) and was not significantly associated with treatment or GPA subtype. Endoscopic CO2 laser excision is a safe and effective local intervention for GPA-associated SGS. Medical maintenance therapy with rituximab reduces risk of recurrence following initial laser excision relative to treatment with non-rituximab agents.

Survey on maintenance immunosuppressive therapy in patients undergoing solid organ transplantation: experiences from Italian transplant centers.

The post-organ transplant immunosuppressive therapy includes the administration of tacrolimus (Tac) or cyclosporine (CsA), along with antimetabolites (Antim) or mTOR inhibitors, with or without prednisone. A survey was conducted to investigate clinical experience regarding the use, efficacy, safety profile, and determinants of choice of maintenance immunosuppressive therapies. The questionnaire was sent to healthcare workers of 45 transplant centers specializing in kidney (K), liver (L), heart (H), and lung (P) transplants. Seventy-one responses were received from 15 Italian regions. The indicated first-choice therapy was Tac + Antim, except in the hepatic field where Tac monotherapy was favored. According to 44.1% of respondents, the first-choice therapy has changed over the last 15 years due to the replacement of CsA with Tac and increased use of mTOR inhibitors. Regarding the determinants of the index therapy, the choice of schemes to be applied depends mainly on international guidelines, previous experience, and internal protocols within the facility (80.3%; 54.9%; 50.7%, respectively). Compared to standard therapy, the criteria guiding the prescription of different therapies mainly involve the presence of comorbidities (K: 81.3%; L: 88.2%; H: 73.3%; P: 85.7%) and the evaluation of specific clinical parameters of the recipient. Additionally, the majority of respondents are in favor of using generic versions where available. The survey reveals dimensions not detectable by current healthcare administrative flows; such integrations provide a broader picture of the factors influencing the choice of post-transplant immunosuppressive therapeutic schemes.

Comparative Inhibitory Effects of Tacrolimus, Cyclosporine, and Rapamycin on Human Anti-Pig Xenogeneic Mixed Lymphocyte Reactions.

Long-term immunosuppressive maintenance therapy is necessary to prevent the rejection of xenografts. However, it is still unclear which oral immunosuppressant is most suitable for pig-to-human xenotransplantation . A xenogeneic mixed lymphocyte reaction (MLR) system was established using peripheral blood mononuclear cells (PBMCs) isolated from wildtype (WT) or GTKO/CMAHKO/β4GalNT2KO (TKO) pigs as stimulator cells and human PBMCs as responder cells. Various concentrations of tacrolimus (Tac), cyclosporine (CsA), or rapamycin (Rapa) were added to the MLR system as interventions. The inhibitory effects of the three immunosuppressants on the proliferation and cytokine production of human T cells were studied and compared. The inhibitory effect of anti-CD154 mAb alone or in combination with Tac/CsA/Rapa on xenoreactive MLR was also investigated. PBMCs from both WT and TKO pigs stimulated significant proliferation of human T cells. Tac had a strong inhibitory effect on human T-cell proliferation stimulated by pig PBMCs. CsA inhibited human T-cell proliferation in a typical dose-dependent manner. When Tac and CsA concentrations reached 5 and 200ng/mL, respectively, the proliferation rates of CD3+/CD4+/CD8+ T cells were reduced almost to a negative level. Even at high concentrations, Rapa had only a moderate inhibitory effect on xenogeneic MLR. The inhibitory effects of these three immunosuppressants on xenogeneic T-cell responses were further confirmed by the detection of CD25 expression and supernatant cytokines (IL-2, IL-6, IFN-γ, TNF-α, IL-4, IL-10, and IL-17). Although anti-CD154 mAb monotherapy showed only moderate inhibitory effects on xenoreactive T-cell proliferation, low-dose anti-CD154 mAb combined with low-dose Tac, CSA, or Rapa could produce significant synergistic inhibitory effects. Tac is more efficient than CsA or Rapa in inhibiting xenogeneic T-cell responses in vitro. If used in combination with anti-CD154 mAb, all the three immunosuppressants can achieve satisfactory synergistic inhibitory effects.

Non-invasive rejection surveillance in stable heart transplantation using local laboratory-run donor-derived cell-free DNA assay: two-centre European feasibility study

Abstract Background Monitoring adverse events is crucial after heart transplantation (HTx). Allograft rejection is a major etiological factor of graft dysfunction, hospitalisation, and death posttransplant. Endomyocardial biopsy (EMB) is the standard method of monitoring rejection; however, there are risks and limitations associated with it. The ISHLT guidelines for the care of HTx recipients have included non-invasive surveillance such as testing for donor-derived cell-free DNA (dd-cfDNA). While major studies have been conducted with patient cohorts and centralised testing in the USA, hereby we explored a European two-site cohort where dd-cfDNA was quantified at local centres by next-generation sequencing-based CE-marked assay. Purpose Our objective was to assess feasibility of assay and evaluate dd-cfDNA values in clinically stable HTx recipients. Methods HTx patients were enrolled at their scheduled visits in this cross-sectional study in 2 European HTx centres. Serial data after HTx, including clinical status, maintenance immunosuppression therapy and drug levels, diagnostic tests (blood tests, echocardiograms, coronary angiograms, EMBs), and adverse events were collected. Venous blood specimens were drawn in Streck cfDNA blood collection tubes for quantification of dd-cfDNA levels. We analysed dd-cfDNA fraction in plasma using AlloSeq cfDNA assay. For analysis, clinical stability was defined as asymptomatic patients >28 days post-HTx with normal graft function, without cytomegalovirus infection, history of rejection, or allograft vasculopathy. Results Between July 2021 and December 2022, 50 HTx recipients were enrolled at a median of 274 (112–395) days posttransplant. The median age at enrolment was 55.5 years. Of the total 82 dd-cfDNA results, 34 samples were excluded as they did not meet stability criteria. The median dd-cfDNA value of stable patients was 0.11% (95% CI 0.08%–0.13%). Median levels of dd-cfDNA did not differ between samples drawn in the first year after HTx (n=40) and at later time (n=8) [0.11% vs. 0.11%; p=0.41]. Of the 48 dd-cfDNA samples, 7 had values at risk based on the dd-cfDNA cut-off values from previous clinical validation trials: 4 at the injury cut-off of ≥0.20% and 3 at the severe injury threshold of ≥0.35%. Comparing clinical variables of samples with dd-cfDNA ≥0.20% (n=7) and <0.20% (n=41), we observed a 3-fold, non-significant increase in rate of de novo DSA formation (33.3% vs. 10.8%; p=0.19). Conclusions Our data show feasibility to analyse dd-cfDNA at the local level. In our two-site European reference cohort, dd-cfDNA is present at low levels (median 0.11%) which is within former reported ranges for clinically stable HTx recipients. Levels of dd-cfDNA do not vary beyond the first post-HTx year. The fact that in patients with de novo DSA higher dd-cfDNA levels are found; although, not statistically significant, suggests that dd-cfDNA may be a marker of subclinical rejection and requires further study.

Safety of Belatacept as a Maintenance Immunosuppressive Therapy in Kidney Transplantation: A Systematic Review and Meta-Analysis

Safety of Belatacept as a Maintenance Immunosuppressive Therapy in Kidney Transplantation: A Systematic Review and Meta-Analysis

Herpes Virus Infections in Kidney Transplant Patients (HINT) – a prospective observational cohort study

BackgroundKidney transplant recipients receive maintenance immunosuppressive therapy to avoid allograft rejection resulting in increased risk of infections and infection-related morbidity and mortality. Approximately 98% of adults are infected with varicella zoster virus, which upon reactivation causes herpes zoster. The incidence of herpes zoster is higher in kidney transplant recipients than in immunocompetent individuals, and kidney transplant recipients are at increased risk of severe herpes zoster-associated disease. Vaccination with adjuvanted recombinant glycoprotein E subunit herpes zoster vaccine (RZV) prevents herpes zoster in older adults with excellent efficacy (90%), and vaccination of kidney transplant candidates is recommended in Danish and international guidelines. However, the robustness and duration of immune responses after RZV vaccination, as well as the optimal timing of vaccination in relation to transplantation remain unanswered questions. Thus, the aim of this study is to characterize the immune response to RZV vaccination in kidney transplant candidates and recipients at different timepoints before and after transplantation.MethodsThe Herpes Virus Infections in Kidney Transplant Patients (HINT) study is a prospective observational cohort study. The study will include kidney transplant candidates on the waiting list for transplantation (n = 375) and kidney transplant recipients transplanted since January 1, 2019 (n = 500) from all Danish kidney transplant centers who are offered a RZV vaccine as routine care. Participants are followed with repeated blood sampling until 12 months after inclusion. In the case of transplantation or herpes zoster disease, additional blood samples will be collected until 12 months after transplantation. The immune response will be characterized by immunophenotyping and functional characterization of varicella zoster virus-specific T cells, by detection of anti-glycoprotein E antibodies, and by measuring cytokine profiles.DiscussionThe study will provide new knowledge on the immune response to RZV vaccination in kidney transplant candidates and recipients and the robustness and duration of the response, potentially enhancing preventive strategies against herpes zoster in a population at increased risk.Trial registrationClinicalTrials.gov (NCT05604911).

Significant Increase in Cytomegalovirus (CMV) Infection in Solid Organ Transplants Associated With Increased Use of Thymoglobulin as Induction Therapy?

Cytomegalovirus (CMV) infection remains one of the most common viral pathogens affecting solid organ transplants (SOT). In 10 years of following the outcome of transplants, we noticed an increased incidence of CMV infection, along with increased use of rabbit anti-thymocyte globulin (rATG). The study aims to assess the incidence of active CMV infection and disease, response to treatment, and recurrence in a cohort of SOT. Furthermore, we look for correlating the CMV incidence with the type of induction therapy: r-ATG or interleukin 2 receptor-blocking antibody (basiliximab). This was a single-center, retrospective 10-year study in patients submitted to kidney, kidney-liver, and kidney-pancreas transplants who used a preemptive therapy protocol for CMV. Among the 476 enrolled transplant recipients, 306 (64.2 %) had at least one episode of CMV infection (replication), and 71/306 patients (23.2 %) presented CMV-related disease. The most frequent clinical conditions associated with CMV disease were gastrointestinal. Among the 476 transplant patients, 333 received immunosuppressive induction with rATG (69.9 %); 140 (29.4 %) received induction with interleukin 2 receptor-blocking antibody (basiliximab). The initial maintenance immunosuppressive therapy in the patients who presented CMV infection was primarily performed with prednisone, tacrolimus, and sodium mycophenolate (91.7 %). The induction with rATG increased from 35.2%-94.6% in 10 years. The incidence of CMV infection was 20.7 % in the first year of observation and gradually increased to 87.3 % in the last year. The data suggest that the increase in the use of rATG in recent years could be responsible for the very expressive increase in the incidence of CMV infection/disease.

A Case Report of Kidney After Heart Transplant in Patient With Fabry Disease

Fabry disease is an X-linked inherited lysosomal storage disorder caused by a mutation in the gene encoding the enzyme α-galactosidase A. It is characterized by the accumulation of globotriaosylceramide in different tissues, resulting in a wide range of clinical presentations. Fabry cardiomyopathy and Fabry nephropathy are the disease's 2 most important life-threatening manifestations and can contribute to higher morbidity and mortality. Heart and kidney transplants can play a major role in patients with Fabry disease who develop end organ damage. We report a case of a successful heart transplant in a male patient with Fabry disease at the age of 62, followed by a kidney transplant later at the age of 69. He has had an uneventful post-transplant course and has been tolerating maintenance immunosuppression and enzyme replacement therapy with recombinant human α-galactosidase A.

#5363 LONG-TERM CLINICAL OUTCOMES OF PATIENTS WITH LUPUS NEPHRITIS TREATED WITH AN INTENSIFIED B-CELL DEPLETION PROTOCOL WITHOUT MAINTENANCE THERAPY

Abstract Background and Aims The aim of this prospective study is to investigate the long term safety and efficacy of intesified B-cell depletion therapy (IBCDT) in patients with active lupus nephritis (LN), in comparison to a conventional immunosuppresant therapy, followed by a 3 year maintenence micophenolate mofetil (MMF) regimen. Method Thirty patients were administered an IBCDT (4 weekly rituximab [RTX] 375 mg/m2 and 2 more doses after 1 and 2 months; 2 infusions of 10 mg/kg cyclophosphamide [CYC], 3 methylprednisolone pulses), followed by oral prednisone (tapered to 5 mg/d by the third month). No immunosuppressive maintenance therapy was given. Thirty patients matched for LN class and age were selected as controls: 20 received 3 methylprednisolone pulses days followed by oral prednisone and mycophenolate mofetil (MMF) 2 to 3 g/d, whereas 10 were given the Euro Lupus CYC. MMF (1-2 g/daily) or azathioprine (AZA, 1-2 mg/kg/day) were given for > 3 years as a maintenance therapy. Results At 12 months, complete renal remission was observed in 93% of patients on IBCDT, in 62.7% on MMF, and in 75% on CYC (P = 0.03); the dose of oral prednisone was lower in the IBCDT group (mean ± SD 2.9 ± 5.0 mg/dl) than MMF (10.5 ± 8.0 mg/d, P < 0.01) or CYC group (7.5 ± 9.0 mg/d, P < 0.01). Mean follow-up after treatment was 44.5 months (interquartile range [IQR] 36-120 months), 48.6 months (IQR 36-120 months), and 45.3 (IQR 36-120 months) for IBCDT, MMF, and CYC, respectively. At their last follow-up visit, we observed no significant differences in proteinuria and serum creatinine, nor in the frequency of new flares among the 3 groups. Conclusion In biopsy-proven LN, the IBCDT without further immunosuppressive maintenance therapy was shown to be as effective as conventional regimen of MMF or CYC followed by >3-year maintenance either MMF or AZA regimen. Moreover, the use of IBCDT was associated with a marked reduction of glucocorticoid cumulative dose.

#6653 USE OF GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS IN KIDNEY TRANSPLANT PATIENTS: A MULTI-CENTER STUDY

Abstract Background and Aims Diabetes mellitus (DM) is a frequent complication in kidney transplant (KT) patients, leading to a higher cardiovascular mortality and graft loss. The use of therapies such as Glucagon-like peptide-1 receptor agonist (GLP-1RA) could have benefits in KT, although the experience reported so far is limited. The aim of our study is to describe the effectiveness and safety of GLP-1RA in KT patients. Method Retrospective cohort study of KT with DM who started GLP-1RA in three Spanish hospitals (Puerta del Mar University Hospital, Jerez de la Frontera University Hospital and Puerto Real University Hospital) from February 2016 to July 2022. All patients had a minimum follow-up of 6 months after starting the treatment. Clinical and demographic variables were analyzed. We collected GLP-1RA type and dose. Glomerular filtration rate (eGFR), proteinuria, and weight were collected at the start of treatment and after 6 and 12 months. We analyze glycemic control, blood pressure and lipid profile. Acute rejections (AR), de novo donor-specific antibodies (DSA) and adverse effects were documented. Parametric and non-parametric tests were performed according to the normality of the sample. Results In this period, 102 KT with DM were treated with GLP-1RA from 19/02/2016 to 22/07/2022. At the time of the prescription mean body mass index was 35.8 kg/m2 and the mean weight was 95 kg. Forty-two (44%) had developed post-transplant diabetes mellitus (PTDM). The mean age was 62 years and 56% were men. Mean baseline estimated glomerular filtration rate (eGFR) was 47.2 ml min/1.73 m2 and the time post-KT was 47 months. The GLP-1RA mostly prescribed was semaglutide (66.7%). Fifty-five (55%) patients reached the maximum recommended dose of the drug. The maintenance immunosuppressive therapy used was steroids (94.7%), tacrolimus (97.4%), mycophenolate (94.7%) and everolimus (2.6%). Eighty-four KT recipients had a minimum follow-up of 6 months and sixty-four were followed for 12 months. We observed stability in eGFR and a reduction in proteinuria (−19.1 mg/g at 6 months, p = .000 and −46.6 mg/g at 12 months, p = .000) during all the follow-up. Additionally, we found a significant reduction in systolic blood pressure (−7.5 mmHg at 6 months, p = .013 and −7,3 mmHg at 12 months, p = .004) despite the number of patients receiving angiotensin receptor blockers, angiotensin-converting enzyme and other antihypertensive therapies. Besides, their doses did not change during the period of the study. In our cohort, body weight significantly reduced (−3.6 Kg at 6 months, p = .000 and −3.6 Kg at 12 months, p = .000). Furthermore, HbA1c decreased (−1.2 mmol/L at 6 months, p = .000 and −1.5 mmol/L at 12 months, p = .000). Notably, insulin dose was also reduced (−2.2 UI/day at 6 months, p = 0.048) but the number of patients with sodium-glucose cotransporter 2 inhibitors increased at 12 months (p = 0.031). Finally, we observed a reduction in total cholesterol (−11.5 mg/dL at 6 months, p = .001 and −15.6 mg/dL at 12 months p = .000) and LDL-c (−9.2 mg/dL at 6 months, p = 0.002 and −16.8 mg/dL at 12 months, p = .000) during the follow-up. However, patients receiving statins and steroids and the dose remained unchanged. Fifteen patients (14.7%) suffered from side effects, mainly nausea and vomiting, and ten patients (9.8%) discontinued the treatment for this reason. No changes in the mycophenolate formulation were made. One patient discontinued the treatment due to the diagnosis of pancreatic cancer 8 months after starting the drug. We did not find differences in the levels or in the dose of tacrolimus. Neither AR episodes nor de novo DSAs development were notified. Conclusion This is the first multicenter study that reports the effectiveness and safety of GLP-1RA in KT patients. Our results support that it can be an option for the management of DM in these patients. Its use is safe and it does not seem to alter tacrolimus trough levels, to induce AR episodes or de novo DSAs development.

#5884 HLA COMPATIBILITY DOES NOT INFLUENCE KIDNEY GRAFT SURVIVAL AND DOES NOT IMPACT THE DEVELOPMENT OF POST-TRANSPLANT NEOPLASIA

Abstract Background and Aims HLA compatibility is a key issue in deceased and living kidney allocation, although the continuous improvement of immunosuppressive protocols might have reduced its relevance. However, an increased immunosuppression is associated with several adverse events, including the development of post-transplant neoplasia. Indeed, several reports demonstrated that the improvement in immunosuppressive drug efficiency corresponded to an increase incidence of malignancies after kidney transplantation. Thus, the aim of our study was to investigate the effect of HLA compatibility on kidney graft survival and incidence of post-transplant neoplasia. Method This is an observational, retrospective, multicenter center study including 1506 patients receiving a single kidney transplant at the Gemelli and Policlinico “Consorziale” kidney transplant centers from 1/1/2000 to 1/2/2022. The primary outcomes were death-censored graft survival and the development of post-transplant neoplasia. HLA compatibility was measured as the number of HLA mismatches (MM) at the three main class I (A and B) and class II (DR) loci. To this purpose, both donor and recipients were genotyped for HLA A, B and DR. We included in the analysis all deceased and living kidney donor transplants and excluded recipients from AB0 incompatible living kidney donors and with pre-transplant donor specific antibodies. Results Based on HLA compatibility, we divided our patients’ population in three groups (0-2 MM, 369 patients 3-4 MM, 856 patients and 5-6 MM, 281 patients). At univariate analysis (Kaplan-Meyer) number of MM were not associate with death-censored graft survival (Logrank p = 0.6) whereas we observed a significant association with the development of post-transplant neoplasia (Logrank p = 0.01). However, multivariate analysis (Cox model including recipient age, induction and maintenance immunosuppressive therapy) demonstrated that patients with 3-4 (HR 1.033, 95% CI 0.676-1.580, p = 0.9) and 5-6 MM (HR 1.342, 95% CI 0.853-2.111, p = 0.2) did not have any statistically significant increase in the risk to develop a post-transplant malignancy. Conclusion In this observational retrospective multicenter analysis, we demonstrated that HLA incompatibility, as indicated by the number of HLA A, B and DR MM, does not predict death-censored graft survival and does not impact the development of post-transplant neoplasia. Our observation would suggest that the missing effect of HLA compatibility on graft outcome is not associated with an increased long-term over-immunosuppression.