Living Donor Liver transplantation in an alloimmunised patient: Immunological challenges and Management in Indian Settings.

Liver transplantation (LT) is often associated with hematological abnormalities with immune or non-immune etiologies and require timely diagnosis and interventions. We report a case of a patient suffering from non-alcoholic steato-hepatitis (NASH) related end stage liver disease (ESLD) with multiple red cell antibodies who underwent LT surgery. In postoperative phase, she developed immune hemolysis as well as acute antibody mediated rejection (AMR) which was managed with therapeutic plasma exchange and IVIG. The case highlights the need to develop an algorithm for red cell and HLA antibody screening in high-risk patients for timely detection and management.

Research highlights on kidney transplantation in 2021: Voices from China

Over the past 70 years, kidney transplantation has become not only the most mature but also the highest-success-rate surgery among all organ transplantation surgeries. However, the long-term survival of kidney transplant recipients is still challenged by such key factors as ischemia-reperfusion injury related to kidney transplantation, rejection, chronic renal allograft dysfunction, renal allograft fibrosis, immunosuppressive therapy, infections and others. Relevant fundamental and clinical studies have emerged endlessly. At the same time, the research related to kidney transplantation also becomes a new hot spot accordingly in the context of the normalization of novel coronavirus pneumonia. This article reviewed the cutting-edge hot spots in relation to the fundamental and clinical aspects of kidney transplantation together with relevant new techniques and new visions. The studies included in this article focused on the reports published by Chinese teams that are more applicable to the current situation of kidney transplantation in China, for the purpose of providing new thoughts and strategies for the diagnosis and treatment of kidney transplantation related issues in China.Copyright © 2022 Organ Transplantation. All rights reserved.

Risk factors for rejection following COVID-19 in lung transplant recipients

Introduction/Aim: The prevalence of and risk factors for acute cellular (ACR) and antibody mediated rejection (AMR) in lung transplant (LTx) recipients is unclear. Method(s): We performed a retrospective cohort study of all living LTx recipients between January 2020 and September 2022. Recipients with COVID-19 infection and those diagnosed with and/or treated for ACR or AMR were identified. Baseline demographics are described. A logistic regression univariate analysis was used to identify risk factors for rejection. Result(s): 128/387 (33%) LTx recipients tested positive to SARS-CoV-2 during the study period. 44 (32.3%) patients were investigated for graft dysfunction, with persistent loss of >=10% of FEV 1 at >=90-days in 37 (31.4%), median was 54.5 years (23-76). There was no significant difference between gender, disease severity or presence of chronic lung allograft dysfunction (CLAD) at time of COVID-19 infection. 9(20.5%) recipients experienced rejection, 3 (6.8%) with AMR, 5 (11.4%) ACR, and 1 (2.3%) both. Median time to onset of rejection was 59 days (16-239). Change in FEV 1 post COVID-19 was not significantly different between recipients with and without rejection, with mean volume loss in rejection group 559 mL (SD 678 mL, 22.9%), and 842 mL (SD 824 mL, 42.9%) in non-rejecters. Univariate logistic regression of risk factors demonstrated younger patients were at higher risk of rejection (OR 0.95 [95% CI 0.90-1.00] p = 0.05). Female gender was weakly associated with rejection (OR 0.21 [95% CI 0.04-1.18] p = 0.08). Time post-transplant, severe COVID illness, early COVID-19 treatment did not show association. Conclusion(s): Acute rejection occurs frequently following COVID infection and should be considered a differential in persistent allograft dysfunction. Younger age and female gender were associated with increased risk of rejection. The volume of lung function lost did not differentiate between those who did and did not suffer rejection;we hypothesise due to non-alloimmune inflammatory processes.

Severe delayed graft function in a living-related kidney transplant recipient due to combination of alloimmunity, autoimmunity, and heterologous immunity: A case report.

BACKGROUND: Delayed graft function is a manifestation of acute kidney injury unique to transplantation usually related to donor ischemia or recipient immunological causes. Ischemia also considered the most important trigger for innate immunity activation and production of non-HLA antibodies. While ischemia is inevitable after deceased donor transplantation, this complication is rare after living transplantation. Heterologous Immunity commonly used to describe the activation of T cells recognizing specific pathogen-related antigens as well unrelated antigens is common post-viral infection. In transplant-setting induction of heterologous immunity that cross-react with HLA-antigens and subsequent reactivation of memory T cells can lead to allograft rejection. METHODS: Here we describe a non-sensitized child with ESRD secondary to lupus nephritis and recent history of COVID-19 infection who experienced 17 days of anuria after first kidney living transplantation from her young HLA-haploidentical uncle donor. Graft histology showed acute cellular rejection, evidence of mild antibody-mediated rejection and vascular wall necrosis in some arterioles suggesting possibility of intraoperative graft ischemia. Both pre- and post-transplant sera showed very high level of several non-HLA antibodies. RESULTS: The patient was treated for cellular and antibody-mediated rejection while maintained on hemodialysis before her graft function started to improve on day seventeen post transplantation. CONCLUSION: The cellular rejection likely trigged by ischemia that activated T-cells-mediated immunity. The high level of non- HLA-antibodies further aggravated the damage and the rapid onset of rejection may be partly related to memory T-cell activation induced by heterologous immunity.

Relationship Between Covid-19 And Donor Specific Antibodies In Orthotopic Heart Transplant Recipients

Introduction: De novo donor specific antibodies (DSAs) are associated with increased risk of antibody-mediated rejection (AMR) and worse prognosis in patients after orthotopic heart transplant (OHT). Viral infections have the potential to induce or reactivate the production of DSAs, yet the development of DSAs after infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has not been reported. In this observational study, we describe DSA titers after Coronavirus Disease 2019 (COVID-19) infection and relationship with AMR and graft dysfunction in a large OHT cohort at a tertiary academic medical center. Hypothesis: : We predicted that COVID-19 infection would be associated with development of de novo DSAs or increase in pre-existing DSAs. Method(s): We retrospectively analyzed all adult OHT patients followed at Washington University School of Medicine in St. Louis between 4/1/2020-12/31/2021. COVID-19 infection was defined by positive antigen or PCR test in setting of clinical exposure or symptoms. Patients were considered fully vaccinated 2 weeks after 2 doses of the BNT162b (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines or after a single dose of the AD26.COV2.S (Johnson & Johnson) vaccine. De novo DSAs were defined as newly detected MHC I or II antibody greater than 2000 mean fluorescence intensity (MFI) by single antigen beads or newly elevated antibody against angiotensin-II type 1 receptor (AT1R). In patients with pre-existing DSAs, a significant increase was defined by an MFI value that increased by 20% or more compared to their baseline value prior to SARS-CoV-2 infection. Result(s): A total of 577 patients were followed during the study period and 117 cases of COVID-19 infection were identified. Baseline characteristics of COVID-19 positive patients are shown in Figure. Overall, 10% of patients infected with SARS-CoV-2 infection developed de novo DSAs or an increase in pre-existing DSAs, with unvaccinated patients having a higher incidence compared to vaccinated patients (15% vs. 2%, p=0.02). MHC class II-specific antibodies were the most common DSAs detected. There was a trend towards higher incidence of AMR in unvaccinated patients, although mortality and long-term graft dysfunction were similar. Conclusion(s): Unvaccinated patients had a higher incidence of developing de novo or an increase in pre-existing DSAs after SARS-CoV-2 infection. Future studies are necessary to investigate the long-term consequences of COVID-19 in the OHT population.Copyright © 2022

Multivessel Epicardial Coronary Artery Thrombosis after Heart Transplantation

Introduction: Although cardiac allograft vasculopathy (CAV) remains one of the leading causes of graft failure after heart transplantation (HTx), simultaneous thrombosis of multiple epicardial coronary arteries (CA) is an uncommon finding. Case Report: A 43-year-old male patient with non-ischemic dilated cardiomyopathy underwent successful HTx in 2019. The first two years after HTx were uneventful, surveillance endomyocardial biopsies (EMB) did not reveal any rejection episodes, coronary CTA revealed only minimal non-calcified CA plaques. The patient was admitted to hospital due to fever and chest pain in 2021. Immunosuppressive therapy consisted of tacrolimus, mycophenolate-mofetil and methylprednisolone. ECG verified sinus rhythm. Laboratory test revealed elevated hsTroponin T, NT-proBNP and CRP levels. Cytomegalovirus, SARS-CoV-2-virus and hemoculture testing was negative. Several high-titre donor-specific HLA class I and II antibodies (DSAs;including complement-binding DQ7) could have been detected since 2020. Echocardiography confirmed mildly decreased left ventricular systolic function and apical hypokinesis. EMB verified mild cellular and antibody-mediated rejection (ABMR) according to ISHLT grading criteria. Cardiac MRI revealed inferobasal and apical myocardial infarction (MI);thus, an urgent coronary angiography was performed. This confirmed thrombotic occlusions in all three main epicardial CAs and in first diagonal CA. As revascularization was not feasible, antithrombotic therapy with acetylsalicylic acid, clopidogrel and enoxaparin was started for secondary prevention. Tests for immune system disorders, thrombophilia and cancer were negative. Patient suddenly died ten days after admission. Necropsy revealed intimal proliferation in all three main epicardial CAs, endothelitis, thrombosis, chronic pericoronary fat inflammation, fat necrosis, and subacute MI. CA vasculitis owing to persistent high-titre DSAs, chronic ABMR and acute cellular and antibody-mediated rejection led to multivessel CA thrombosis and acute multiple MI. ABMR after HTx may be underdiagnosed with traditional pathological methods. Pathologies affecting coronary vasculature of HTx patients with DSAs, unique manifestations of CAV lesions and occlusive thrombosis of non-stenotic, non-atherosclerotic lesions should be emphasized.Copyright © 2023

Renal transplantation

Individuals with kidney failure face a future requiring long-term treatment with either dialysis or renal transplantation. Renal transplantation is the preferred form of renal replacement therapy, and is associated with a better quality of life, and usually increased longevity. Unfortunately, owing to excessive co-morbidities, only 30% of patients who develop end-stage renal failure are fit enough for transplantation. Over 90% of kidney transplants still function after 1 year, and most function for >15 years. Improvements in transplant outcomes are attributable to advances in histocompatibility testing, organ procurement, organ preservation, surgical techniques and perioperative care. Long-term outcomes have shown only minor improvements over the last two decades, although this should be considered in the context of deteriorating organ quality as older deceased donors with increasing co-morbidity are used more often to satisfy the need for donor organs. An overall increase in deceased donor numbers has boosted transplant activity in the UK, and it is hoped this will continue with the adoption of the 'opt-out' consent system. Living donor activity remains stable, but the use of non-directed altruistic donation and the living donor exchange scheme have reduced the need for higher immunological risk incompatible transplantation. The COVID-19 pandemic has reduced transplant rates globally, although national transplant systems are now recovering.Copyright © 2022

Renaissance of Equine Antithymocyte Globulin in Renal Transplantation

Introduction: Anti Thymocyte Globulin(ATG) is very effective as an Induction and antirejection therapy (ART) agent in renal Transplantation. Equine ATG (eATG) has been used less compared to rabbit ATG(rATG) in tranplantation. Cost of eATG as induction agent is 200 USD, in comparison to rATG, which costs minimum 700 USD per dose (approximately four times more than eATG). Experience with eATG initially was not good because of drug reactions but over the years the molecule has evolved into a better drug and is the preferred drug over rATG in severe Aplastic Anemia without any reactions. Covid pandemic has affected the supply chain of rATG because of vaccine production leading to shortage of rATG. Hence eATG is the only available ATG. Method(s): We present our experience with eATG in a tertiary care nephrology centre for the last 95 renal transplants. Patients have been divided into two groups. Group A- contained HLA matched first degree relatives as renal donors and induction agent was injection Methylprednisolone (MP). Group B- Had Recipients of Deceased or Spousal donors and received eATG 10mg/kg as induction agent single dose. Monitoring of renal function and observation for complications including, infections was done. Blood lymphocyte count was monitored for intial 2 weeks to look for lymphocyte depletion as an indicator of eATG efficacy. Patients were followed upto 5 years post transplant (PTX) and assessment was done at 1,3 and 5 years for graft and patient survival. eATG usage as anti rejection therapy (ART) agent in acute T- cell-mediated rejection(TCMR) : All acute TCMRs (biopsy proved) were treated with eATG 10mg/kg body for 5 consecutive days followed by repeat biopsy and additional eATG therapy depending on patient response. Result(s): Induction Therapy: Table 1,2,3 Number of recipients in GrA were 41 and GrB were 54. Marked decrease in Lymphocyte count in Gr B indicated efficacy of eATG (p<0.05). In the first 90 days post transplant, Acute TCMR ( biopsy proved) was seen in 5(9.7 %) of GrA and 7(12.9 %) of GrB (p>0.05). In GrA 1(2.4%) patient had acute antibody mediated rejection (ABMR) but could not be treated with ART because of presence of active infection. In Gr B 1(1.8%) patient had histopathological features suggestive of ABMR but was C4D negative and patient responded to eATG alone. Infections were noticed in 9.7% (5/41) of GrA patients and 11.1% (6/54) of GrB patients in the first 180 days PTX (p>0.05). Urinary tract infections, respiratory tract infections and soft tissue infections were commonly seen. Post ART oppurtunistic infections were not seen. Comparison of incidence of Acute rejection rates, graft survival, complications rate and patient survival rate show similar results in both the groups. We achieved good efficacy with eATG as induction and ART agent in biopsy proved acute TCMR. No adverse events and no malignancies were observed after eATG therapy. Conclusion(s): eATG can be used as induction and antirejecton therapy agent in TCMR in renal transplantation. eATG is economical compared to rATG. No conflict of interestCopyright © 2023

Clazakizumab for the treatment of chronic active antibody-mediated rejection (AMR) in kidney transplant recipients: Phase 3 IMAGINE study rationale and design.

BACKGROUND: Chronic active antibody-mediated rejection (AMR) is a major cause of graft loss with no approved drugs for its treatment. Currently, off-label regimens are used, reflecting the high unmet need for effective therapies based on well-controlled trials. Clazakizumab is a high-affinity, humanized monoclonal antibody that binds interleukin-6 and decreases donor-specific antibody (DSA) production and inflammation. Phase 2 pilot studies of clazakizumab in kidney transplant recipients with chronic active AMR suggest modulation of DSA, stabilization of glomerular filtration rate (GFR), and a manageable safety profile. We report the design of the Phase 3 IMAGINE study (NCT03744910) to evaluate the safety and efficacy of clazakizumab for the treatment of chronic active AMR. METHODS: IMAGINE is a multicenter, double-blind trial of approximately 350 kidney transplant recipients with chronic active AMR (Banff chronic glomerulopathy [cg] >0 with concurrent positive human leukocyte antigen DSA) randomized 1:1 to receive clazakizumab or placebo (12.5 mg subcutaneous once every 4 weeks). The event-driven trial design will follow patients until 221 occurrences of all-cause graft loss are observed, defined as return to dialysis, graft nephrectomy, re-transplantation, estimated GFR (eGFR) <15 mL/min/1.73m2, or death from any cause. A surrogate for graft loss (eGFR slope) will be assessed at 1 year based on prior modeling validation. Secondary endpoints will include measures of pharmacokinetics/pharmacodynamics. Recruitment is ongoing across North America, Europe, Asia, and Australia. DISCUSSION: IMAGINE represents the first Phase 3 clinical trial investigating the safety and efficacy of clazakizumab in kidney transplant recipients with chronic active AMR, and the largest placebo-controlled trial in this patient population. This trial includes prognostic biomarker enrichment and uniquely utilizes the eGFR slope at 1 year as a surrogate endpoint for graft loss, which may accelerate the approval of a novel therapy for patients at risk of graft loss. The findings of this study will be fundamental in helping to address the unmet need for novel therapies for chronic active AMR. TRIAL REGISTRATION: ClinicalTrials.gov NCT03744910 . Registered on November 19, 2018.

Late antibody-mediated rejection in a kidney transplant recipient: COVID 19 induced?

BACKGROUND: Antibody-mediated rejection (AMR) was described in kidney transplant patients after viral infections, such as the cytomegalovirus. Very few cases were recently reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, probably in the context of lowering of immunosuppressive therapy. To date, no direct immunological link was proved to explain a connection between the coronavirus disease 19 (COVID-19) infection and antibody-mediated rejection (AMR) if it exists. CASE PRESENTATION: Here we try to find this association by presenting the case of a low immunological risk patient who presented, six years post-transplant, with c4d negative antibody mediated rejection due to an anti-HLA-C17 de novo donor specific antibody (DSA) after contracting the coronavirus disease 19. The HLA-Cw17 activated the antibody-dependent cell-mediated cytotoxicity via the KIR2DS1 positive NK cells. DISCUSSION AND CONCLUSIONS: This case report may prove a direct role for COVID-19 infection in AMRs in the kidney transplant recipients, leading us to closely monitor kidney transplant recipients, especially if they have "at-risk" donor antigens.

New Onset Cmv Disease in Post Renal Transplant Patients in Association with Covid19 Infection - 2 Cases and Brief Review of Literature

BACKGROUND: Several cases of CMV syndrome and invasive CMV infection have been reported following COVID19 infection worldwide during COVID19 pandemic in both immunocompetent and immunosuppressed patients. AIM OF THE STUDY: We intend to discuss more about the interrelationship of COVID19 and CMV infection in renal transplant patients. METHOD(S): We discuss two clinical cases, and we present a brief review of literature. 30-year-old man with end-stage primary lupus nephritis underwent mother-to-son kidney transplantation. Post-transplant surgery the patient was discharged with 1.8 mg/ml baseline creatinine. After 3 months, he was admitted with complaints of fever for 4 days with no derangement of renal function. He tested positive for COVID 19 infection and was managed conservatively. Subsequently within 10 days, he was readmitted with chief complaints of loose stools abdominal pain and back pain with mildly raised creatinine and leukopenia. CMV PCR detected 128500 copies per ml. This patient was treated with injection ganciclovir and GM-CSF injection. Mycophenolate mofetil was withheld in view of CMV infection. However, the patient complained of persistent back pain with gradual decline in graft and renal function. With decreasing urine output, dialysis was initiated. Subsequently, the patient developed altered sensorium and had cardiac arrest. 34-year-old male with end-stage chronic nephritis had undergone cadaveric kidney transplantation. Post-transplant the patient had delayed onset graft function with baseline creatinine of 2 mgdl on the 10th post-operative day. Subsequently, the patient suffered from active antibody-mediated rejection, and the patient was managed with six cycles of plasmapheresis. One month later, the patient was admitted with fever and cough. The patient tested positive for COVID19 infection and was managed conservatively. Simultaneously, the patient developed multiple episodes of hematochezia pain in abdomen and diarrhea. Urine output was maintained with stable creatinine. Stool routine and microscopic examination revealed multiple RBCs few pus cells - however no parasite was detected. CMV PCR was positive with 3000 copies per ml. The patient was initially treated with injection ganciclovir and was switched to oral valganciclovir. The patient remained afebrile general condition improved with no further episodes of hematochezia and gradual decline of creatinine to baseline level. RESULT(S): In both our cases, COVID19 infection were managed conservatively, and CMV infection was treated with stoppage of mycophenolate mofetil and addition of ganciclovir injection and resulted into one positive and one negative clinical outcome. CONCLUSION(S): CMV reactivation after COVID 19 infection in renal transplant patient may be a common phenomenon. Further studies are immediately needed to know whether CMV viremia should be routinely tested in all renal transplant patients in India who get COVID19 infection. Studies are also required to determine if clinical outcomes of CMV disease after COVID19 infection in renal transplant patients are different from CMV disease outcomes in other renal transplant patients who have no history of immediately preceding COVID 19 infection.

Study of Efficacy of Equine Anti Thymocyte Immunoglobulin (Eatg) as Induction and Antirejection Therapeutic Agent in Renal Transplantation

BACKGROUND: Equine Anti-Thymocyte Immunoglobulin (eATG) has been used less as an induction immunosuppressant agent in renal transplantation compared to rabbit ATG (rATG). However, eATG is very economical compared to rATG. The cost of eATG as induction agent in renal transplant on an average is INR. 30 000/- per dose, and cost of rabbit ATG ( rATG) as induction agent is INR 1 20 000/-. AIM OF THE STUDY: To study the efficacy of eATG as induction and anti-rejection therapeutic agent in renal transplantation. METHOD(S): Material(s) and Method(s): Renal transplant recipients were divided into two groups. Group A (GrA) recipients had renal donation from HLA matched first degree relatives and received only injection methylprednisolone (MP) as induction therapy. Group B (GrB) recipients had renal donation from deceased donors (brain dead) or spousal donors were administered eATG 10 mg/kg along with low dose MP as induction therapy. Outcomes were compared between GrA and GrB. Monitoring for eATG therapy-induced blood lymphocyte count depletion post-transplant was also done to assess eATG efficacy. eATG as antirejection therapy agent: eATG was administered in biopsy-proved acute T-cell-mediated rejection (TCMR). Repeat transplant kidney biopsy was done to assess improvement. RESULT(S): Number of renal transplant recipients in GrA were 29 and GrB were 35. All recipients of GrA and GrB had normal renal function by 14th post-transplant day (PTX). There was 20% decrease in blood lymphocyte count following MP therapy (GrA) compared to 85% decrease following therapy with eATG ( GrB) and the difference was statistically significant (p < 0.05). Marked decrease in lymphocyte count indicated efficacy of eATG. Biopsy-proved acute TCMR was seen in 5% of GrA and 4% of GrB (p > 0.05). None from both groups had antibody mediated rejection. All patients with acute TCMR responded to eATG antirejection therapy. Opportunistic infections was noticed in 9% of GrA patients and 11% of GrB patients in the first 180 days PTX (p > 0.05). Two years graft survival was 83% in GrA and 80% in GrB (p > 0.05). During two-year followup one patient from each group died of Covid19 infection (p > 0.05). CONCLUSION(S): Since excellent results were obtained with eATG as an induction and antirejection therapeutic agent, it can be used in renal transplant with high-risk immunological states as a polyclonal antibody. eATG is more economical compared to rATG.

Subclinical Kidney Allograft Rejection Without Maintenance Immunosuppressive Therapy (mIST)

Introduction: Kidney transplant (KTx) generally requires mIST to prevent rejection and graft loss. A mother-to-son kidney recipient presents with preserved kidney function despite being off mIST for 26 years. Case Description: A 44-year-old man with diabetes mellitus, unknown congenital kidney disease requiring peritoneal dialysis for 3y and KTx from his mother at age 13, and status post COVID19 infection 2m prior, presents with diabetic ketoacidosis due to insulin nonadherence. Patient received unknown mIST until age 18 when he self-discontinued therapy. Initial studies: Serum: glucose1064 mg/dL, pH 7.28, +ketones, creatinine (Cr) 2.4 mg/dL (baseline Cr 1.1);Urinalysis 4-10 white blood cells/high power field, few bacteria;Urine protein/Cr 0.4 g/g, albumin/Cr 0.1 g/g Patient received insulin and fluid with Cr improved to 1.1 mg/dL. Fig 1 shows Cr timeline. Kidney biopsy was performed prior to discharge to determine the need for mIST reinitiation. While awaiting for pathology report as outpatient, Cr increased to 1.82 mg/dL. Pathology Fig 2: Chronic active T-cell-mediated tubulointerstitial rejection, active vascular rejection, and chronic active antibody-mediated rejection. Patient was readmitted for intravenous immunoglobulin & antithymocyte globulin with appropriate Cr improvement and discharged on prednisone, mycophenolate, & tacrolimus. Donor HLA-typing was not available for donor specificic antibody testing. Discussion(s): The case demonstrates 1) Subclinical rejection may occur in the setting of prolonged IST discontinuation and 2) Cr is insensitive in detecting rejection and raises the possibility of COVID19-induced exacerbation of ongoing low-level rejection. (Figure Presented).

Plasmapheresis and Rituximab for Prevention of Focal Segmental Glomerulosclerosis Recurrence Post-Kidney Transplantation

Purpose: Primary focal segmental glomerulosclerosis (FSGS) recurs after kidney transplantation (KT) in 30-50% of recipients with a median time of 1.5 months post- KT. Recurrence is associated with early graft loss in 60% of cases. The aim of this study is to assess the efficacy of pre-emptive therapeutic plasma exchange (TPE) and rituximab for the prevention of FSGS recurrence post-KT. Method(s): This single-center, retrospective study included patients receiving KT for primary FSGS between May 2016 and August 2021. Living-donor KT recipients received three sessions of TPE prior to scheduled transplant. Recipients of both living and deceased donor KT received 3 postoperative sessions of TPE followed by one dose of 375 mg/m2 rituximab with or without intravenous immune globulin (IVIG) 0.5 g/kg. Recipients underwent protocol biopsy at one month to screen for FSGS recurrence. The primary endpoint was a composite for disease recurrence including proteinuria (>=1 g/day) or/and biopsy-proven FSGS within one month. Result(s): 54 patients received KT for FSGS during the study period using the TPE/ rituximab protocol. 5 patients (9%) experienced FSGS recurrence within one month of transplant. A total of 10 patients (19%) were found to have disease recurrence within a year, with median (IQR) time to recurrence of 37 days (27-66). White race and history of hypertension were independent risk factors for recurrence, whereas African American race and diabetes were associated with a reduced risk of recurrence. 31 patients (57%) also received IVIG prior to discharge due to concerns for hypogammaglobulinemia. There were 18 documented infections in 13 patients (24%) within 3 months of transplant. Patients who received IVIG had significantly fewer cases of infection (3 cases: 1 viral and 2 COVID-19) compared to patients who did not receive IVIG (15 cases: 4 bacterial, 9 viral, 1 fungal, and 1 COVID-19), p<0.001. At one year, 9 patients (19%) had biopsy-proven rejection (5 acute cellular rejection, 1 antibody-mediated rejection, and 3 mixed rejection). There were no instances of graft loss or mortality observed at one year. Conclusion(s): The utilization of plasma exchange and rituximab may prevent early disease recurrence of FSGS without significant rates of infection, graft loss, or mortality.

Adverse Renal Events After BNT162b2 Pfizer/BioNTech COVID-19 Vaccine in Kidney Transplant Recipients

Purpose: Adverse events of a novel mRNA vaccine are not well described in Kidney Transplant Recipients(KTR), especially the risk of immune activation or recurrent glomerulonephritis(GN), which has been described in native GN after COVID-19 vaccines. Method(s): In this single-center prospective study, 147 KTR were enrolled after informed consent and administered 2 doses of Pfizer/BioNTech vaccine 21 days apart. Follow-up was 3 weeks after Dose2. Result(s): Mean age of KTR was 51 years;55.1% male;65.3% Chinese, 19% Malay, 11.6% Indian;69.5% Living donor, 29.9% Deceased donor, 0.7% Pancreas-kidney transplants;71.5% had biopsy-proven or presumptive chronic GN(CGN), 12.9% diabetic nephropathy, 15.6% other causes. 11(7.5%) KTR had delayed Dose2 administered at median 29 days(range 24-93) after Dose1. 7(4.8%)were delayed due to renal events: rise in creatinine(n=3), or proteinuria(n=2), or both creatinine and proteinuria with allograft biopsy showing acute T-cell and antibody-mediated rejection(n=1), new BK viraemia(n=1). Other reasons were possible anaphylaxis(n=1), intercurrent infection(n=2), and inability to attend due to quarantine(n=1). 27 KTR had new microhaematuria(MH) after Dose1;9 persisted after Dose2. Additional 18 had new MH after Dose2. Of 45 KTR with new MH, 7 had underlying IgAN, 5 had other biopsy-proven-CGN and 22 had presumed CGN, suggesting 34/45 with possible immune activation. 12 KTR had new onset proteinuria (rise in urine protein:creatinine ratio (UPCR) <=30 to >30mg/mmol);5/7 who developed a rise after Dose1 remained elevated;additional 5 had a rise after Dose2. 7 KTR had rise in proteinuria from UPCR <=100 to >100mg/mmol. Conclusion(s): Subclinical changes in allograft monitoring parameters are frequent after COVID-19 mRNA vaccines with up to 40.1% of KTRs showing rises in creatinine, proteinuria or new MH. Although overt recurrent GN and acute rejection are infrequent, high vigilance and monitoring for these occurrences should be undertaken in KTRs receiving mRNA vaccines.

Pathological Changes in Kidney Allografts Associated with COVID-19 Vaccination

Purpose: The Coronavirus Disease 2019 (COVID-19) pandemic prompted widespread vaccination for the immunosuppressed population starting in January 2021 with minimal information on safety outcomes. The purpose of this study is to evaluate the relationship between kidney pathological changes and mRNA-based COVID-19 vaccines in three kidney transplant recipients. Method(s): We conducted a single-center retrospective case review of three kidney transplant recipients with biopsy-proven acute rejection or pathological changes after 2-dose COVID-19 mRNA vaccination. Renal function, maintenance immunosuppressant regimens, and pathology slides at baseline and post-rejection are recorded. Possible factors associated with the development of rejection were analyzed. Result(s): All participants were male, two received related-living donor transplants and one received a deceased donor transplant. The mean age was 44.3 years. Average time from 2nd COVID-19 vaccine to confirmed rejection or pathological changes was 33.7 days. Two patients received mRNA-1273 COVID-19 mRNA vaccine and one received the BNT162b2 COVID-19 mRNA vaccine. All three allograft biopsies demonstrated findings consistent with acute active antibody mediated rejection and thrombotic microangiopathy. One allograft biopsy also demonstrated findings consistent with collapsing focal segmental glomerular sclerosis. As of November 26, 2021, there have been over 26 reports of solid organ rejection or failure to the Vaccine Adverse Event Reporting System (VAERS) for the COVID-19 mRNA vaccines highlighting the need for further investigation. Conclusion(s): Immunization with COVID-19 mRNA vaccine has potential to precipitate clinically significant immune response to renal allografts leading to acute allograft rejection, thrombotic microangiopathy, and collapsing focal segmental glomerular sclerosis.

Outcomes and Complications of Covid-19 in Pediatric Solid Organ Transplant Patients

Purpose: The purpose of the study was to examine the clinical course, outcomes, and complications of COVID-19 in pediatric solid organ transplant patients from a single institution, with special attention to thrombotic complications, multiple inflammatory syndrome in children (MIS-C), and new rejection. Method(s): The medical record at our institution was retrospectively queried for all solid organ transplant patients up to 21 years old diagnosed with COVID-19 from March 2020 to September 2021. This cohort was compared in a 1:1 fashion with age, sex, and ethnicity-matched controls with COVID-19 infection, but no history of transplant. Categorical variables were analyzed with Chi-square or Fisher's exact test, and continuous variables were analyzed with Mann-Whitney test. Result(s): 44 solid organ transplant patients met study inclusion criteria. Six patients were excluded from analysis due to insufficient documentation of COVID-19 diagnosis or course. The cohort was composed of 17 kidney, 11 heart, six liver, two lung, one liver-kidney, and one multivisceral transplant patients. Median age at COVID-19 diagnosis was 15 years (IQR 9). Median time from transplant to COVID-19 diagnosis was 2.5 years (IQR 3.4). Of the 38 patients, 17 were white non-Hispanic/Latino (44.7%), 12 were Hispanic/Latino (31.6%), three were Black (7.9%), two were Asian (5.3%), three were other (7.9%), and one was unknown (2.6%). 19 patients (50%) were male. 12 transplant patients were asymptomatic (31.6%), compared to five controls (13.2%, p=0.054). Of the symptomatic patients, the most common symptoms in the solid organ transplant group were fever (26.3%) and headache (18.4%), with few patients experiencing shortness of breath (5.3%). Hospital (15.8%) and ICU (5.3%) admission rates were equal in both groups, with a median length of stay of 4.5 days for the transplant group (IQR 5.25) versus 4 days (IQR 5.75) for controls (p=0.59). 32 patients in each group received supportive care as outpatients (84.2%). A minority of transplant patients received monoclonal antibody (6.3%), convalescent plasma (6.3%), steroids (6.3%), and remdesivir (3.1%). There was one case of MIS-C in the transplant group (2.6%) versus three in the control group (7.9%) (p=0.62). One transplant patient developed COVID-associated microangiopathy (2.6%), but there were no thrombotic complications among controls (p > 0.99). There were no new cases of cellular or antibody-mediated rejection following COVID-19. There was one death in the transplant cohort, but no deaths in the control group. Conclusion(s): We report the largest multi-organ cohort of pediatric solid organ transplant recipients with COVID-19 to date. Our findings suggest pediatric solid organ transplant patients fare similarly to healthy children, without elevated risk of complications.

Successful Implementation of a Rural Appalachian Kidney Transplant Program, One Year Outcomes

Purpose: Kidney transplantation has become the optimal treatment for end stage renal disease (ESRD), allowing dialysis free survival. Despite widespread availability of transplant programs;rural patients have limited access to transplantation due to several barriers including increased travel time and financial burden. We report outcomes after establishment of a kidney transplant program serving rural West Virginia. Method(s): A retrospective review of the first 15 kidney transplants performed at a newly established Appalachian transplant program was conducted. Primary outcomes measured were graft survival and function. Other outcomes included graft rejection, patient survival and complications. Data related to patient demographics, etiology of ESRD, type of renal replacement therapy, time on transplant waitlist and average travel to transplant center were also collected. Result(s): The first 15 kidneys transplanted had an overall death censored graft survival rate of 100%. Median patient age was 53 (Range 31- 73 years) and a median follow-up of 6 months (Range 1-13 months). The average time on dialysis for this cohort was 4 years (n=13, Range 1-6 years) and average time on waitlist was 4.06 months (Range 0.4-13.2 months). The most common type of dialysis was hemodialysis (77%) followed by peritoneal dialysis (15%). Two patients were predialysis. Diabetes with hypertension (20%), IgA nephropathy (13%) and diabetes without hypertension (13%) were the most common causes of ESRD. Median graft creatinine was 1.51 mg/dL (Range 1.26 - 1.83 mg/dL) with a glomerular filtration rate (GFR) at 51.38 (Range 41.86-70) at one year. One patient developed acute antibody mediated rejection and one developed borderline T cell mediated rejection (13.3%), which were successfully treated with steroids, plasmapheresis and immune globulin therapy. Two patients died (13.3 %);one from acute respiratory failure following coronavirus (COVID-19) infection and one from cardiac arrest secondary to myocarditis (possible COVID-19). Patients experienced COVID-19 infection at a rate of 13.3 %. The average distance patients had to travel was 94 miles (Range 12 - 164 miles) with a travel time of 1 hour and 52 minutes on average (Range 20 minutes - 2.5 hours) to reach the transplant center. Conclusion(s): We report comparable outcomes from our new rural transplant program despite several barriers to delivery of quality care to our population.

Covid-19 in Pediatric Kidney Transplant: A Follow-Up Report of the Improving Renal Outcomes Collaborative

Purpose: To date studies of children with a kidney transplant and COVID-19 are limited. The Improving Renal Outcomes Collaborative (IROC) is a learning health network in the US comprised of 36 pediatric kidney transplant programs that provides infrastructure to efficiently conduct multicenter studies. Method(s): We collected COVID-19 testing, indications, and outcomes data. Data were linked to patient demographic and clinical data in the IROC registry. We previously reported the results of this effort from April 6-September 3, 2020 (era 1). Here we report data from September 4, 2020 - February 28, 2021 (era 2). We describe the differences in testing frequency and positive testing over the two eras. Result(s): In era 1, 22 centers submitted testing data;in era 2, 21 centers submitted testing data. There were 281 tests in 281 patients analyzed in era 1 and 648 tests for 465 patients in era 2. From era 1 to era 2, the proportion of positive tests increased from 24/281 (8.54%) to 109/465 (23%). Testing frequency and results from eras 1 and 2 are displayed in Figure 1. 133 patients tested positive for COVID-19 over both eras, and there was no difference in the symptoms at the time of testing between the two eras. The most common symptoms for both eras were fever (35%), cough (33%), rhinorrhea (23%), vomiting (14%), and diarrhea (14%). Over both eras, 41/133 (31%) that tested positive for COVID-19 had no symptoms at the time of testing. There were no differences in outcomes between the two eras. 117 patients (88%) had no transplant complications. 1 (0.8%) patient had T cell-mediated rejection, 3 (2%) had antibody-mediated rejection, 1 (0.8%) had mixed T cell- and antibodymediated rejection, 10 (7.5%) had acute kidney injury, 1 (0.8%) experienced graft failure, and 1 patient (0.8%) died from their COVID-19 infection. Conclusion(s): In this cohort, there was overall more testing and more positive COVID-19 tests in era 2. The dates of era 2 correspond with children returning to school and the Winter surge in cases in the US. Despite the increased number and proportion of positive patients, the clinical outcomes are consistent with reported outcomes for their non-immunosuppressed peers. Follow-up studies will be required to evaluate whether the availability of vaccines for adolescents and the rise of the delta variant as the predominant strain affect clinical outcomes. (Table Presented).