Rejection Episodes Research Articles

Positive Long-Term Outcome of Kidney Allocation via Acceptable Mismatch Program in Highly Sensitized Patients

Introduction: Eurotransplant established the acceptable mismatch (AM) program to facilitate timely kidney transplantations of highly sensitized patients, but long-term granular clinical and immunological outcomes regarding overall graft survival and de novo DSA (dnDSA) formation are still intensively researched. The right choice of induction therapy in patients with differing immunological risk is not conclusively determined, as well as the impact of human leukocyte antigen (HLA) epitope matching on dnDSA formation. Methods: This monocentric, retrospective study analyzed 94 patients transplanted within the AM program between 2000 and 2019 compared to case-control matched cohorts of non- (PRA 0–5%; PRA-0) and intermediately sensitized (PRA 6–84%; PRA-6/84) patients transplanted through Eurotransplant Kidney Allocation System. Results: Estimated 10-year overall graft survival between the PRA-0 and AM cohorts was similar, whereas PRA-6/84 was significantly disadvantageous compared to PRA-0. Estimated 10-year incidence of antibody-mediated rejection rates was significantly lower in the PRA-0 group compared to AM and PRA-6/84 groups. Compared to the AM group, estimated incidence of de novo donor-specific antibody (dnDSA) was significantly lower in PRA-0 patients, with no differences between the AM and PRA-6/84 cohorts. The PRA-6/84 cohort was the only subgroup in which interleukin-2 receptor antagonist (IL2RA) induction was associated with longer overall graft survival, patient survival, and graft survival compared to depleting induction (ATG or OKT3). Broad HLA-A, -B, -DR mismatches (mmABDR) and HLA epitope mismatches determined by Eplets and PIRCHE-II were predictive for dnDSA formation in the total cohort, and the AM subgroup. Discussion: The high efforts expended on AM patients are justified to allow timely organ transplantation with acceptable risk profile and non-inferior outcomes. IL2RA induction in intermediately sensitized patients is associated with superior overall graft survival, patient survival, and graft survival compared to ATG/OKT3 induction, without negative effects on rejection episodes or dnDSA formation. In silico epitope matching might further help reduce dnDSA formation, particularly in high-risk AM patients.

Role of Octreotide and Instillation of Povidone-Iodine in the Treatment of Lymphorrhea in Renal Transplantation: A Comparative Study

Background: Lymphorrhea is a minor complication after kidney transplantation but may develop into a lymphocele and prolong hospital stay. Treatment is conservative based on percutaneous drainage until lymphatic leakage cessation. It has been reported that povidone iodine instillation and octreotide has beneficial effects to treat lymphorrhea after renal transplantation. Aims and Objectives: The aim of this study was to compare the povidone iodine instillation and octreotide treatment in lymphorrea after kidney transplantation. To evaluate the efficacy of povidone iodine and octreotide injection in comparison to control group for the treatment of lymphorrhea in renal transplant patient. Materials and Methods: It was comparative analytical study included 60 recipients of both cadaveric and live kidney allografts with posttransplant lymphorrhea including 20 treated with instillation of betadine solution, 20 with octreotide (0.1 mg three times a day subcutaneously), and 20 was control group (no betadine and octreotide was used). We reviewed the daily amount of fluid collection, duration of lymphorrhea, complications, lymphocele formation, rejection episodes, graft outcomes, and hospital stay. Results: The average duration of lymphorrhea was (8.85 ± 0.88) and (11.6 ± 0.94) and (16.15 ± 0.81) days for the betadine groups, the octreotide groups and control groups respectively. (P < 0.05). No lymphoceles occurred among the betadine group, while three lymphoceles were found among patients treated with octreotide and five lymphocele were found among control groups. No differences were observed for wound infection, graft dysfunction episodes or renal function and death between the groups. No octreotide and povidone related adverse events were noted. Conclusion: The mean length of lymphorrhea was lower with povidone iodine instillation as compared to octreotide treatment. There was a shorter hospital stay and minor patient discomfort in betadine groups. In conclusion, lymphatic leakage after kidney transplantation may be successfully managed by betadine instillation as compared to octreotide and control groups.

Influence of Cyp3A4, Cyp3A5 and ABCB1 Polymorphisms on Tacrolimus Concentrations and Rejection Risk in Indian Kidney Transplant Recipients

Background: Tacrolimus metabolism is known to be determined by gene polymorphisms. Cyp3A5 genotype has most widely been seen to be associated with tacrolimus metabolism. Studies on other genes have produced mixed results. Objective: We studied the association of three polymorphisms CYP3A4*1B (-392 G>A), CYP3A5 (6986 A>G), and ABCB1 (3435 T>C) on tacrolimus levels and their association with either rejection or nephrotoxicity (infection or tacrolimus toxicity) in renal transplant recipients from India. Materials and Methods: In this prospective cohort study, patients who underwent kidney transplantation between July 2018 and July 2023 were studied. Inclusion criteria: Patients who underwent Kidney Transplantation and were (i) on tacrolimus-based immunosuppression and (ii) not on medications known to interact with calcineurin inhibitors, such as ketoconazole, phenytoin, and diltiazem, were studied. Tacrolimus levels, tacrolimus concentration/dose (C/D) and tacrolimus C/D per kg body weight, at monthly time points posttransplant for 6 months and biopsy-proven rejection, infection, tacrolimus toxicity, and acute tubular necrosis data were collected. Results: Three hundred and twenty-seven patients were included in the study. Two hundred and fifty-seven were male and 70 were female. A total of 1402 tacrolimus samples were collected, with an average of 3.2 ± 2.1 samples per patient. Tacrolimus levels were significantly lower in the Cyp3A5 AG and AA GG genotypes versus GG (5.27 ± 2.95 and 6.22 ± 2.79 vs. 8.05 ± 4.83, P < 0.001) as were C/D (3.45 ± 2.29 and 3.37 ± 1.91 vs. 6.47 ± 4.44, P < 0.001) and C/D/W (52.45 ± 33.98 and 52.19 ± 32.61 vs. 98.09 ± 73.80, P < 0.001). Cyp3A5 AA and AG had higher rejection rates than GG (20% vs. 13 vs. 8%, P = 0.03). The relative risk of rejection with A versus G polymorphism was 1.9 (confidence interval: 1.03–3.58), P = 0.03. Cyp3A4 and ABCB1 polymorphism studies did not show any association with the parameters studied. Conclusion: Our study showed that Cyp3A5 gene polymorphisms were significantly associated with tacrolimus metabolism, rejection episodes, and rejection risk. Cyp3A4 and ABCB1 were not significantly associated with the parameters studied.

Management of Kidney Transplant Outpatients With COVID-19: A Single Center Experience.

Patients undergoing kidney transplant are at risk of severe COVID-19. Our single-center retrospective analysis evaluated the outcomes of kidney transplant outpatients with COVID-19 who were managed with reduced immunosuppression and treatment with molnupiravir. Between January 2022 and May 2023, we included 93 patients (62 men, average age 56years), serum creatinine 127 (101-153) µmol/L. Molnupiravir was administered, and immunosuppressive therapy was reduced immediately following the confirmation of SARS-CoV-2 infection by PCR, which was 2 (1-3) days after the onset of symptoms. Only three (3.2%) patients required hospitalization, and one patient died. Acute kidney injury was observed in two patients. During the follow-up period of 19 (15-22) months, there was no significant increase in proteinuria, no acute or new chronic graft rejection, and kidney graft function remained stable; serum creatinine was 124 (106-159) µmol/L post-COVID-19 infection and 128 (101-161) µmol/L at the end of the follow-up period. Our results demonstrate that early initiation of molnupiravir treatment combined with a temporary reduction in immunosuppressive therapy results in favorable clinical outcomes in patients with COVID-19, with preservation of good graft function and no episodes of graft rejection.

Association between CYP3A5 Gene Polymorphism and Post-Transplant Acute Immune Rejection in Renal Transplant Recipients Receiving Tacrolimus Therapy: A Correlation Study.

Acute immune rejection remains a challenge in the post-transplant period, with approximately 7.8% of renal transplant recipients experiencing rejection episodes within the first year. Genetic polymorphisms in the CYP3A5 gene, which influences tacrolimus metabolism, have garnered interest regarding their association with clinical outcomes in renal transplantation. This retrospective correlation study analysed clinical data from kidney transplant patients who received tacrolimus treatment at our hospital from June 2015 to June 2023. The presence of CYP3A5 gene polymorphisms, tacrolimus trough levels, and demographic and clinical data were collected and analysed. A total of 105 kidney transplant patients were included. Patients were divided into acute immune rejection (n = 56) and non-acute immune rejection (n = 49) groups. The distribution of CYP3A5 gene polymorphisms differed significantly between the acute rejection and non-acute rejection groups (p = 0.037). The acute rejection group exhibited a higher frequency of CYP3A5 *1/*1 or *1/*3 genotypes than the non-acute rejection group. No statistically significant differences were found in the tacrolimus trough levels between the two groups. Correlation analysis revealed a statistically significant correlation between CYP3A5 gene polymorphism and post-transplant acute immune rejection (r = 0.223, p < 0.05). This study demonstrated a significant association between CYP3A5 gene polymorphism and the risk of post-transplant acute immune rejection in renal transplant recipients receiving tacrolimus therapy. These findings highlighted the importance of genetic variability in tacrolimus metabolism when managing immunosuppressive therapy in transplant recipients.

Low-Dose vs Standard-Dose Valganciclovir for Cytomegalovirus Prophylaxis After Kidney Transplantation: A Single-Center Retrospective Analysis

Prophylactic administration of valganciclovir (VG) is an accepted method for the prevention of cytomegalovirus (CMV) infection after kidney transplantation (KTx). The standard dosage of oral VG is 900 mg/day, adjusted to renal function. There is growing evidence that low-dose 450 mg/day VG might be safe and effective. We compared low-dose vs standard-dose prophylaxis after KTx in a single-center follow-up study. Data from 603 renal transplantations at a single center were retrospectively analyzed (2011-2014, 12-month follow-up). Recipients with donor IgG positive-recipient IgG positive (D+/R+), (D+/R-), and (D-/R+) CMV serostatus were routinely treated with 450 mg/day VG for 3 months. Based on the same prophylactic dose, patients could be categorized into two groups according to their postoperative renal function: those receiving standard-dose VG due to a lower estimated glomerular filtration rate (eGFR) (average eGFR<60 mL/min/1.73 m2) and those receiving low-dose VG due to higher eGFR (average eGFR>60 mL/min/1.73 m2). Estimated glomerular filtration rate-based VG serum alterations significantly affected the risk of CMV infection with a higher incidence in higher VG levels (standard-dose: 357 patients, CMV: 33 cases (9.2 %); low-dose: 246 patients, CMV: 10 cases (4.1%). The occurrence of known risk factors: serologic risk distribution and rate of induction therapy were not statistically different between the 2 groups. Treatment of an acute rejection episode influenced the infection rate significantly in the standard-dose group. As a side effect of prophylaxis, leucopenia (<3G/L) was 2.46 times higher in standard-dose vs low-dose group. Low-dose VG administration is safe and non-inferior to the standard dose in the prophylaxis of CMV infection after KTx.

Peak insulin drip rate associated with decreased infections post-solid organ transplant.

Infection and rejection outcomes were retrospectively analyzed in patients following liver transplant and separately following heart transplant with patients being stratified by their severity of immediate postoperative insulin resistance as measured by the peak insulin drip rate that was required to reduce glucose levels. For each group, these peak insulin drip rates were divided into quartiles (Q). In liver transplant patients (n=207), those in Q4 (highest infusion rate) had significantly fewer infections up to 6 months post-transplant (42.3%vs. 60.0%, p=.036) and borderline fewer rejection episodes (25.0%vs. 40.0%, p=.066) compared to Q1-Q3 patients. To confirm these unexpected results, a subsequent similar analysis in heart transplant (n=188) patients again showed that Q4 patients had significantly fewer infections up to 6 months (19.1%vs. 53.9%, p<.0001) compared to Q1-Q3 patients. Logistic regression in a subset of 103 cardiac transplant patients showed that the maximum glucose during surgery, prior MI, and hypertension were associated with severe insulin resistance (SIR) status, while the presence of pre-existing diabetes and BMI were not. We hypothesize that patients are who are able to mount a more robust counter-regulatory response that causes the insulin resistance may be healthier and thus able to mount a better response to infections.

The Role of Protocol Allograft Biopsies in Postrenal Transplantation: A Systematic Review and Meta-analysis

Introduction: Kidney transplantation is the preferred treatment for end-stage kidney disease, offering improved outcomes compared to dialysis. However, factors such as immunological rejection, drug toxicity, and infections limit its success. Incorporating protocol biopsies (PBs) into standard care for kidney transplant recipients varies widely. This study aims to review the literature on the practice, histopathological findings, and benefits of performing PB on allograft function. Materials and Methods: A systematic review was conducted using PubMed, ScienceDirect, and other databases from 2000 to 2023. Studies describing findings of PBs within 2 years posttransplant were included. Data extraction covered study design, immunosuppression, biopsy timing, incidence of subclinical rejection (SCR), clinical rejection, and allograft function measures. Statistical analysis was performed using R and RevMan software. Results: Among 25 studies (3384 patients) included, 8 were randomized controlled studies. Protocol biopsy timing varied, with the highest number performed at 1 year (44.84%). The pooled incidence of SCR was 13%, with heterogeneity across estimates. Subgroup analysis did not reveal significant differences in SCR rates between high- and low-immunologic risk patients. Patients who underwent PBs had lower clinical rejection rates (12.64% vs. 20.17%) and better allograft function. Incidence of calcineurin inhibitor toxicity ranged from 1.2% to 63.4%, and BK virus nephropathy ranged from 0% to 5.9% in included studies. Conclusion: Performing PB at 6 months, 1 year, and 2 years posttransplant can reveal SCR and potentially improve long-term graft outcomes. Treatment of SCR may reduce clinical rejection episodes. However, further research, particularly comparing PB with noninvasive methods, is needed to better understand their efficacy and complications in the modern transplant landscape.

Discipline Dynamics of Chymistry and Rejection of Alchemy

This paper applies Patton and Al-Zayadi’s scientonomic framework for understanding disciplines to a case study of the development of the chemical discipline ("chymistry") from the 17th century through the early 18th century in Western Europe. Using evidence from the tradition of textbook publication that emerged in the seventeenth-century chymistry, we reconstruct the top-level of the question hierarchy of chymistry. Analyzing how these questions and their associated theories were received, we first show how, starting in the 1660s, alchemy transitioned from a synonym of chymistry to chymistry’s subdiscipline with a more limited scope. We identify that the rejection of alchemy's core questions occurred in the 1720s based on the reception of these questions in scientific publications and by academic institutions. Hence, we conclude that the subdiscipline of alchemy became rejected in the 1720s. In order to conduct our case-study, we closely follow Newman and Principe's research on early modern alchemy and chymistry in our reconstruction of the episode. However, using the scientonomic framework in analyzing this case study reveals the specific dynamics of this instance of sub-discipline rejection. Our deepened understanding of this hallmark historical episode of disciplinary rejection indicates the value of Patton and Al-Zayadi’s theoretical framework for observational scientonomic research.

Prevalence and spectrum of infectious and inflammatory dermatologic conditions occurring in pediatric heart transplant patients on a predominantly mTOR-based immune suppressive regimen: A retrospective chart review.

Pediatric heart transplant patients are routinely followed in dermatology clinics due to elevated risk of cutaneous malignancy. However, transplant patients may experience other, non-cancer-related dermatologic conditions including skin infections, inflammatory diseases, and drug eruptions that can cause significant medical and psychosocial comorbidity. A retrospective chart review of all pediatric heart transplant patients at Mayo Clinic Children's Center in Rochester, MN, was performed to determine the prevalence and spectrum of non-cancer dermatologic conditions. Statistical analysis was conducted to look for associations between episodes of rejection and skin condition development. Of the 65 patients who received heart transplants under the age of 18 and were followed at Mayo Clinic, 69% (N = 45) were diagnosed with at least one skin condition between transplant and the time of most recent follow-up. Sixty-two percent (N = 40) of patients were diagnosed with an inflammatory skin condition (most commonly acne and atopic dermatitis), 45% (N = 29) with an infectious skin condition (most commonly warts and dermatophyte infection), and 32% (N = 21) with a drug eruption (most commonly unspecified rash and urticaria). No association was found between presence of skin disease and number of rejection episodes. Non-cancer dermatologic conditions are prevalent within pediatric heart transplant recipients and may directly impact their medical needs and quality of life. Dermatologist involvement in the care of post-transplant pediatric patients is important, not only for cancer screening but also for diagnosis and treatment of common infectious and inflammatory skin conditions.

T-cell receptor sequencing reveals selected donor-reactive CD8+ T cell clones resist antithymocyte globulin depletion after kidney transplantation

High frequencies of donor-reactive memory T cells in the periphery of transplant candidates prior to transplantation are linked to the development of posttransplant acute rejection episodes and reduced allograft function. Rabbit antithymocyte globulin (rATG) effectively depletes naïve CD4+ and CD8+ T cells for >6 months posttransplant, but rATG’s effects on human donor-reactive T cells have not been carefully determined. To address this, we performed T cell receptor β-chain sequencing on peripheral blood mononuclear cells aliquots collected pretransplant and serially posttransplant in 7 kidney transplant recipients who received rATG as induction therapy. We tracked the evolution of the donor-reactive CD4+ and CD8+ T cell repertoires and identified stimulated pretransplant, CTV-(surface dye)-labeled, peripheral blood mononuclear cells from each patient with donor cells or third-party cells. Our analyses showed that while rATG depleted CD4+ T cells in all tested subjects, a subset of donor-reactive CD8+ T cells that were present at high frequencies pretransplant, consistent with expanded memory cells, resisted rATG depletion, underwent posttransplant expansion and were functional. Together, our data support the conclusion that a subset of human memory CD8+ T cells specifically reactive to donor antigens expand in vivo despite induction therapy with rATG and thus have the potential to mediate allograft damage.

Anti-thymocyte globulin for treatment of T-cell-mediated allograft rejection.

Anti-thymocyte globulin (ATG) is a pivotal immunosuppressive therapy utilized in the management of T-cell-mediated rejection and steroid-resistant rejection among renal transplant recipients. Commercially available as Thymoglobulin (rabbit-derived, Sanofi, United States), ATG-Fresenius S (rabbit-derived), and ATGAM (equine-derived, Pfizer, United States), these formulations share a common mechanism of action centered on their interaction with cell surface markers of immune cells, imparting immunosuppressive effects. Although the prevailing mechanism predominantly involves T-cell depletion via the com plement-mediated pathway, alternate mechanisms have been elucidated. Optimal dosing and treatment duration of ATG have exhibited variance across ran domised trials and clinical reports, rendering the establishment of standardized guidelines a challenge. The spectrum of risks associated with ATG administration spans from transient adverse effects such as fever, chills, and skin rash in the acute phase to long-term concerns related to immunosuppression, including susceptibility to infections and malignancies. This comprehensive review aims to provide a thorough exploration of the current understanding of ATG, encom passing its mechanism of action, clinical utility in the treatment of acute renal graft rejections, specifically steroid-resistant cases, efficacy in rejection episode reversal, and a synthesis of findings from different eras of maintenance immunosuppression. Additionally, it delves into the adverse effects associated with ATG therapy and its impact on long-term graft function. Furthermore, the review underscores the existing gaps in evidence, particularly in the context of the Banff classification of rejections, and highlights the challenges faced by clinicians when navigating the available literature to strike the optimal balance between the risks and benefits of ATG utilization in renal transplantation.

COVID-19 vaccination and corneal allograft rejection- a review.

To provide a comprehensive literature review on the perceived correlation between COVID-19 vaccination and corneal allograft rejection, and to characterize risk factors, time course, graft outcomes and proposed immunological basis. A literature review was conducted in August 2023 using 4 electronic databases: PubMed, EMBASE, MEDLINE and Scopus. Articles were sourced using key words associated with COVID-19 vaccination and corneal graft. All articles were screened for relevance by abstract review. Duplicates and articles related to COVID-19 infection were excluded. No time limits were set. Additional literature searches regarding cause of corneal graft rejection, rates of graft rejection associated with other vaccines and the cellular mechanism of rejection were also performed. 262 articles were identified from the literature search. 37 papers were included in the analysis based on defined inclusion criteria. This consisted of systematic reviews (n=6), review articles (n=5), retrospective studies (n=3), case series (n=8), letter to the editor (n=1) and case reports (n= 14). The majority of reported allograft rejections were in penetrating keratoplasties. Risk factors for COVID-19 vaccination associated rejection were previous allograft rejection episodes, repeat grafts and penetrating keratoplasty. Most reported rejection episodes were mild and resolved with treatment. Notably, several studies reported nil increase in corneal allograft rejection episodes over the COVID-19 vaccination period. Rejection episodes are associated with a broad spectrum of other vaccines and the complete pathophysiology is undetermined. Corneal allograft rejection appears to be a rare complication of COVID-19 vaccination most frequently observed in high-risk corneal transplants. The true extent of this correlation remains controversial; however, clinician awareness of this risk is essential to its mitigation. Patient counselling around symptom monitoring following vaccination and discussion around topical steroid prophylaxis may be prudent.

Perioperative changes in radiographic density in erector spinae muscle and mortality after lung transplantation

RationaleThe radiographic density of the erector spinae muscle (ESM) is often decreased early after lung transplantation (LTx). The prognostic impact of this change has not been elucidated. ObjectiveTo investigate whether the decrease in the radiographic density of ESMs early after LTx is associated with a poor prognosis. MethodsThis study is a single center retrospective cohort study. Routine follow-up chest computed tomography scan data just before and 12 weeks after LTx were retrospectively retrieved for adult patients who underwent primary LTx at Kyoto University Hospital. The radiographic density of ESM was quantitatively evaluated as the mean attenuation of the ESM (ESMct), and the impact of the decreased ESMct during the 12 weeks after LTx on overall survival (OS) was examined by Cox proportional hazard regression. ResultsA total of 151 recipients (94 cadaveric LTx, 57 living-donor lobar LTx) were included in this study. The median duration of postoperative observation was 4.4 years, during which time 39 recipients (26%) died. Decreased postoperative ESMct was significantly associated with poor OS (HR, 1.64; 95% CI, 1.14–2.35, P = 0.008 per 1 Z score decrease) in the multivariate model adjusted for age, sex, episodes of acute rejection, and preoperative ESMct. Similar results were obtained when the subjects were limited to those with cadaveric LTx. ConclusionA decreased perioperative ESMct was strongly associated with a poor prognosis after LTx in addition to low preoperative ESMct. Maintaining postoperative muscle radiographic density, which reflects muscle quality, may be important for a better prognosis after LTx.

Non-ischaemic preservation of the donor heart in heart transplantation: protocol design and rationale for a randomised, controlled, multicentre clinical trial across eight European countries

IntroductionIschaemic cold static storage (ICSS) is the gold standard in donor heart preservation. This ischaemic time frame renders a time constraint and risk for primary graft dysfunction. Cold oxygenated heart...

Outcomes of lung transplantation from donors with hepatitis C viremia with outpatient initiation of antiviral therapy

Transplantation of lungs from donors with active hepatitis C viremia with early initiation of antiviral therapy has been shown to have similar short- and medium-term outcomes compared to transplantation of lungs from non-viremic donors. Consideration of hepatitis C viremic lungs is particularly helpful in patients with anticipated prolonged time on the waiting list. Whether clinical outcomes remain favorable with delay of initiation of antiviral therapy to the outpatient setting or in patients with higher severity of illness is not well understood. Our transplant center considered hepatitis C nucleic acid testing positive (NAT+) donors for all waitlisted lung transplant candidates without chronic liver disease. For those transplanted with hepatitis C NAT+ lungs, we initiated anti-viral therapy in the outpatient setting and continued treatment for 12 weeks. In a retrospective single center study of 15 lung transplant recipients receiving hepatitis C NAT+ lungs and 88 recipients receiving non-viremic lungs, we tested the hypothesis that deferral of antiviral therapy after transplantation of lungs from hepatitis C NAT+ donors to the outpatient setting would result in similar 1 year survival compared to transplantation of lungs from non-viremic donors. Patients receiving hepatitis C NAT+ lungs had similar baseline characteristics, but had longer index hospital lengths of stay (24 vs. 13 days, p=0.021). Patients receiving hepatitis C NAT+ lungs had fewer episodes of acute cellular rejection in the first year. Patients receiving hepatitis C NAT+ lungs had similar one year survival to patients receiving lungs from non-viremic donors, after controlling for age and lung allocation score (p=0.638). In this small single-center study, outpatient initiation of antiviral therapy for donor-derived hepatitis C is associated with acceptable clinical outcomes and can be considered in patients with high severity of illness.

2706. Effectiveness and Safety of Shingrix Vaccination in Solid Organ Transplant Recipients at a Large Urban Transplant Center

Abstract Background The varicella zoster virus (VZV) recombinant subunit vaccine, Shingrix, was found to be safe in solid organ transplant recipients (SOTR) and is now approved and recommended for all immunocompromised patients. Given limited efficacy data, we preferred a single center retrospective study to demonstrate safety and effectiveness of the Shingrix vaccine in solid organ transplant recipients. Methods After IRB approval, clinical data from all SOTR at Northwestern Memorial Hospital (NMH) who received the Shingrix vaccine after their transplant, between January 1, 2017 and March 1, 2022 was collected from our Enterprise Data Warehouse (EDW). Extracted data includes age, race, ethnicity, date of transplant, organ transplanted, and date(s) of vaccine administration(s). Clinical outcomes were assessed by diagnosis of acute allograft rejection and/or HZ made post-vaccine administration. Descriptive statistics were utilized. This project is supported by the IDSA G.E.R.M. program. Results 309 of 338 eligible SOTR were included in the analysis of this study (characteristics and reasons for exclusion in Table 1). Only 1 (0.32%) patient experienced a new episode of acute allograft rejection within 3 months of Shingrix administration. 18/309 (5.8%) were diagnosed with HZ after vaccination with Shingrix. This represents a reduction in VZV reactivation events compared to the 9.1% incidence found in the 2021 meta-analysis of HZ in the general solid organ transplant population [Kwon, Transpl Infect Dis., 2021].Table 1.Characteristics of 338 solid organ transplant patients who received Shingrix vaccine. Conclusion The Shingrix vaccine, when administered to SOTR post-transplant, is safe and likely effective in reducing the rate of herpes zoster. This data supports the current recommendation to vaccinate all SOTR with Shingrix. Larger, multi-center data are needed to inform the true efficacy of the vaccine in SOTRs. Disclosures All Authors: No reported disclosures

Meet in the middle: Could cell mediated-immunity assays be the answer for ideal Cytomegalovirus prophylaxis after lung transplantation? Observational study from a single center with intermittent antiviral prophylaxis.

Cytomegalovirus (CMV) can cause tissue-invasive disease and indirect effects after lung transplantation (LTx) such as acute rejection episodes and chronic lung allograft dysfunction. Monitoring CMV-specific cell immune recovery (CMV-CIR) after LTx can individualize CMV risks and establish better antiviral approach. This study evaluated the dynamics of CMV-CIR, using QuantiFERON-CMV assay (Qiagen Group), in the first year after LTx. Prospective observational cohort study included lung transplant recipients from December/2015 to December/2016. Universal antiviral prophylaxis with intravenous ganciclovir 5mg/kg/day 3 days/week for 3 months was given for CMV-seropositive recipients (R+) and only CMV-seropositive donor and negative recipient (D+/R-) received a 6-month-prophylaxis with ganciclovir and valganciclovir, on alternate days, in the first 3 months and then, 3 more months of valganciclovir. QuantiFERON-CMV was measured at the same time points of surveillance bronchoscopies. CMV infection was defined as any DNAemia detected and CMV disease with proven biopsy or antigenemia pp65 above 10 cells/300.000 neutrophils. Thirty-eight patients were included. On days 45, 90, and 365 days post-LTx, 60%, 72%, and 81% QuantiFERON-CMV were reactive, respectively. Eleven patients (28.9%) presented CMV-disease and 27 DNAemia/CMV infections. Reactive tests were able to predict CMV disease only at 90 days after LTx (p=.027) but failed on DNAemia/CMV infection (p=.148). Daily prophylaxis, for D+/R- patients (13.2%), remained as an independently associated factor for not achieving reactive QuantiFERON-CMV (adjusted OR .27, 95%CI .12-.60, p=.02). QuantiFERON-CMV may be another diagnostic tool to help stratify CMV-disease risk and individualized antiviral prophylaxis after LTx.

Expression and clinical implications of HLA-G and PD-L1 following kidney transplantation: A cohort study.

Kidney transplantation (KT) is the preferred treatment for end-stage renal diseases. Human leukocyte antigen G (HLA-G) and programmed death-ligand 1 (PD-L1) have notable clinical and therapeutic significance in transplantation because of their roles in promoting tolerance. This study aimed to assess HLA-G and PD-L1 levels at various stages following KT. A cohort of 12 patients was monitored from the pretransplant phase to 12 months post-surgery. Blood samples were taken at specific intervals: before kidney transplantation (T0), and then on the 7th (T7), 30th (T30), 90th (T90), 180th (T180), and 365th days post transplantation. Renal biopsies were performed in patients with graft dysfunction. Plasma levels of soluble HLA-G (sHLA-G) and PD-L1 were quantified using enzyme-linked immunosorbent assays. Additionally, immunohistochemistry was used to detect the presence of both molecules in biopsy samples. Multivariate analysis indicated that episodes of rejection were correlated with decreased expression of sHLA-G (P < .001) and PD-L1 (P < .001). Over the course of the study, the sHLA-G levels also declined (P < .001). Patients who had been transfused had lower PD-L1 levels (P = .03). Furthermore, kidney recipients from related live donors had increased HLA-G expression (P < .001). Our findings suggest that diminished HLA-G and PD-L1 levels correlate with an increased risk of graft rejection. Notably, HLA-G expression significantly decrease after the third-month posttransplantation.

Unraveling Intestinal Microbial Shifts in ESRD and Kidney Transplantation: Implications for Disease-Related Dysbiosis.

The composition of the gut microbiome is profoundly influenced by the accumulation of toxins in end-stage renal disease (ESRD) and specific medical treatments during kidney transplantation (KT). However, variations in results may arise due to factors such as genetics, dietary habits, and the strategy of anti-rejection therapy. Therefore, we conducted a 16S rRNA sequencing study to characterize intestinal microbiomes by using 75 fecal specimens obtained from 25 paired Chinese living donors (LDs) of kidneys and recipients before and after KT. Surprisingly, similar enterotypes were observed between healthy LDs and ESRD recipients. Nonetheless, following KT, the fecal communities of recipients exhibited distinct clustering, which was primarily characterized by Escherichia-Shigella and Streptococcus at the genus level, along with a reduction in the diversity of microbiota. To further explore the characteristics of gut microorganisms in early rejection episodes, two recipients with biopsy-proven borderline changes during follow-up were enrolled in a preliminary sub-cohort study. Our findings reveal a comparable construction of gut microbiota between ESRD patients and their healthy relatives while also highlighting the significant impact of KT on gut microbial composition.