A Comprehensive Review of 275 Kidney Transplants Performed over 3 1/2 Years;a Single Center Experience

Introduction: Access to kidney transplantation has always been a problem in the African countries with many patients having to travel to other medically advanced countries in Asia, Europe and America. This involves unnecessary excessive expenditure and the travails of journey and stay in an unknown foreign land. To ease this situation and to provide affordable Renal transplant services in their home land, we have made an effort to start the transplant services at our medical facility and have successfully carried out about 275 transplants over a period starting from Nov 2018 till September 2022. Method(s): All the Kidney transplants done between the period Nov 2018- September 2022 (275 cases) were included in the analysis. All the transplants were performed at a single center and the data were collected progressively during their Pre transplant evaluation, perioperative course and post op follow up. All the laboratory and radiological tests were done locally at the center except the HLA cross matches and tissue typing, which were outsourced to Transplant immunology labs outside the country. All the patients with positive DSA titres [about 70%], underwent Plasmapheresis and received IVIg before the transplantation. immunological assessment was done by NGS high resolution, for A B C DP DQ DR loci and X match was done by SAB analysis for class 1 and Class II antigens. All the patients underwent laparoscopic donor nephrectomy. All Patients received vaccinations for Hepatitis B, Pneumonia, Infuenza & Covid. Result(s): A series of 275 kidney transplants were performed over a period of 42 months [ Nov 2018- September 2022] at a private hospital successfully. All the cases were live donor kidney transplants with majority of the donors being 1st or 2nd degree relatives or spousal donors. About 70% of the patients had some degree of sensitization in the form of weakly positive B cell X match, or positive for DSAs at CL I, CLII with MFIs > 1000. All high-risk patients received induction with rabbit Thymoglobulin, and IV methyl prednisolone. Around 50 patients received Basiliximab. Of all patients, 4were HBsAg positive, and 6 were HIV positive,& HCV 1 patient. 8 patients required pretransplant Parathyroidectomy for refractory hyperparathyroidism, 3 patients required simultaneous native kidney nephrectomy at the time of transplant. 25 patients had multiple renal vessels which were double barreled and anastamosed.4 patients had lower urinary tract abnormalities requiring simultaneous/subsequent repair. Overall, 4 patients underwent 2nd transplant. All the donors underwent laparoscopic nephrectomy. Most of the patients had good immediate graft function except in 40 patients, who had delayed graft function;most of them improving over 2 - 6 weeks. 6 Patients had hyperacute rejection and the graft was lost,.4patients had main renal artery thrombosis, Renal allograft biopsy was done in 20 patients. Overall, the Patient survival was 95 %.at 1 year and graft survival 90%. Conclusion(s): Our experience shows that kidney transplantation is a viable and practical option for End stage kidney disease and can be performed even in resource constrained centers in third world countries and the survival rates of patients and the grafts are comparable to other centers across the world. No conflict of interestCopyright © 2023

A Study of Long-Term Outcome of Mycophenolate Dose Modulation in Renal Allograft Recipients With SARS-CoV2 Infection During COVID-19 Pandemic

Introduction: A significant reduction of acute rejection rates was observed after using Mycophenolate mofetil (MMF) in renal transplant recipients (RTR). However, side-effects like hematological and gastrointestinal intolerance often occur when MMF is used in routine doses.MMF dose reduction is required during its side-effects or co-existing infection in RTR.The outcome of MMF dose modulation in RTR is not well established. COVID-19 pandemic has given an opportunity to study the effect of MMF dose modulation on graft function as large number of RTR who had Covid19 received MMF dose reduction or discontinuation. This study's objective was to determine whether MMF dose reduction or discontinuation was associated with the effect on allograft function after renal transplantation. We included all RTR who had an infection with SARS-CoV2 and received MMF dose reduction or discontinuation Methods: We prospectively collected data of Renal transplant recipients developing covid 19 infection during the first and second covid waves. Management including decision on admission, immunosuppression modulation, antibiotics were done based on clinician's discretion subject to logistics and the prevailing guidelines by the ISOT. All patients were followed up for minimum 15 months for graft dysfunction, biopsy rate, biopsy proven acute rejection ( BPAR). The effect of immunosuppression modulation - MMF cessation (Group A) Vs MMF reduction/no manipulation (Group B) and its bearing on the incidence of rejection and was compared. Additional factors such as follow - up sub therapeutic CNI levels, development of DSA ( when done ), steroid increment were studied regression model. Kaplan - meier survival curves for 24 months drawn. Result(s): Among 251 renal transplant patients with SARS-CoV2 infection, 38 patients died during Index admission. 45 patients has not completed for 15 months.168 patients completed 15 month follow - up. Among them, anti-metabolite were reduced in 115 ( 68.5%), stopped in 42 (25%), not manipulated in 5 ( 3%) and 6 patients were not on anti-metabolites and hence excluded from present analysis. Of the 162 patients, MMF had been stopped for 2 weeks or until presumed clinical recovery in 42 patients ( Group A) and the rest in 120 patients ( Group B). Mean age was 41.18 ( +/- 12.8) and 75.6 % had mild COVID. Median duration of follow-up was 18 months ( 14q1-22q3 months). Total Readmission rate was 66 ( 40.7%) (Group A 21( 50%) Vs Group B 45 ( 37.5 %). Graft Biopsy was done in 16% of patients. 9.3 % patients had acute rejection ( 11.9% Vs 8.3%, p 0.05). Among those who had rejection, ABMR was seen in 2, ACR in 3, CABMR in 5 and combined rejection in 1. Conclusion(s): MMF dose modulation to tackle an infectious episode may be associated with graft dysfunction and rejection on follow-up and close follow up is needed in any patient in whom MMF dose in manipulated No conflict of interestCopyright © 2023

Clinical Profile, Immunosuppressive Managment and Outcome in Adult Renal Allograft Recipients with Covid-19 Infection: A Case Series from Single Centre in Bangladesh

Introduction: The Novel Coronavirus disease 2019 (COVID-19), a respiratory infection has become a global concern. Given to the extent of the COVID-19 pandemic, it has been explored that Renal Allograft Recipients are considered high risk group for unfavourable outcome due to multiple comorbidities, long term immunosuppressive medications and residual CKD. This case series demonstrates clinical characteristics and outcome of COVID-19 infection in Renal Allograft Recipients. Method(s): Here we present 20 adult Renal Allograft Recipients admitted with moderate to severe symptom and RT PCR confirmed COVID-19 infection at united hospital limited from August 2020 to December 2021. We assessed demographic characteristics, comorbidities, clinical and laboratory parameters, radiological findings, immunosuppressive management and outcome. Result(s): Among all,15 patients were male with median age 55 years (range,34-75years). Mean time interval between renal transplantation were 90 months (24-132 months). Common comorbidities were hypertension (n=19), DM (n=18), lung diseases (n=13), IHD (n=9). Fever (100%) was most common symptom followed by cough(80%), sore throat(75%), and diarrhoea(60%). Nine (45%) patients who presented with dyspnoea during admission further progressed to poor outcome. During admission mean baseline creatinine was 1.51mg/dl(0.66-3.1 mg/dl), 15 patients had lymphopenia and 11 patients had higher inflammatory markers like high ferritin level, CRP, procalcitonin, LDH and D-dimer. Total 15 patients had abnormal HRCT findings and most common finding was unilateral or bilateral Ground glass opacity followed by consolidation, pleural effusion and interlobular septal thickening with mean TSS scoring being 8 (range 4-16). All patients were on triple immunosuppressive regimen (antimetabolites, CNI, low dose steroid).After admission antimetabolites were withdrawn in all patients, CNI were continued in 10 patients, 50% reduction in 2 patients, complete cessation of CNI in 8 patients and low dose steroids were switched to dexamethasone 6mg/ day. Other treatments included antiviral (Favipiravir, Remdisivir), antibiotics, LMWH followed by Rivaroxaban. Total 3 patients received Tocilizumab and Convalescent plasma was administered in 2 patients. Among all, 18 patients received different form of oxygen therapy, 9 patients were transferred to ICU, 7 patients required mechanical ventilation and 4 patients developed ARDS. 8 patients had other bacterial or fungal coinfection. six patients developed AKI and 2 of them needed Renal replacement therapy (RRT). Total 4 patients of AKI and 1 patient who required RRT finally expired. Total 6 patients died and after a median 18 days of admission. Conclusion(s): In this case series we describe 30% mortality rate. Older age, severe symptom specially dyspnoea during presentation, multiple comorbidities, high inflammatory markers, high baseline creatinine developing AKI, high TSS score at HRCT and requirement of mechanical ventilation were associated with high risk of death. No conflict of interestCopyright © 2023

Peritoneal dialysis after failed kidney transplantation, a case series with review of the literature

Kidney transplantation is a definite treatment for end-stage renal disease (ESRD). However, management of allograft dysfunction has remained a major challenge and some patients return to dialysis after renal transplantation. Studies showed that peritoneal dialysis (PD) results in a higher chance of survival and a lower risk of delayed allograft dysfunction compared to hemodialysis (HD). For this reason, this study explored the initiation of PD in six patients with renal allograft dysfunction in Tabriz Imam Reza hospital (referral PD center). This case reported the results of PD and incremental PD among these patients with failed kidney transplantation. Creatinine and hemoglobin levels, duration of starting PD, PD exchange, PD modality, immunosuppressive drugs mortality rate and urine volume were evaluated during the study. In conclusion, although re-transplantation is a gold standard therapy in failed kidney transplant patients, PD or incremental PD could be a suitable and home-based modality for preserving renal function and urine output in these patients.Copyright © 2022 The Author(s);Published by Society of Diabetic Nephropathy Prevention.

Isolated Colonic Histoplasmosis in Renal Transplant Recipient Post Covid-19 Infection

Introduction: Histoplasmosis is caused by the dimorphic fungus - Histoplasma capsulatum. The presentation of histoplasmosis is often disseminated, though primary intestinal involvement can rarely be seen in patients with cell mediated immune dysfunction like in patients with AIDS. We report a case of renal allograft recipient, who had history of COVID 19 infection and also underwent anti-rejection treatment for renal graft dysfunction, presented with chronic diarrhea and was diagnosed as a case of colonic histoplasmosis. Method(s): We report a case of 45 years old male who underwent renal transplant surgery one and a half year prior (February 2021) and was having stable graft function on tacrolimus, mycophenolate and steroid. He had history of fever and diarrhea in February 2022 and was diagnosed COVID-19 positive with RT-PCR, and was treated conservatively with intravenous dexamethasone and lowering of immunosuppressants. He had mild graft dysfunction in April 2022;renal graft biopsy had acute T-Cell mediated rejection (Banff Grade 1 B) and was treated with pulse steroids for 3 days. He had complaint of intermittent diarrhea, weight loss and intermittent fever since May 2022. He was evaluated and treated on outpatient basis with empirical oral antibiotics. He was admitted in June 2022 with complaint of high grade fever, loose stools leading to hypovolemic shock and renal dysfunction. He had marked thrombocytopenia and neutrophilic leukocytosis. He showed initial response to intravenous broad spectrum antibiotics and crystalloids, but intermittently symptoms of increased stool frequency and altered consistency were still persisting. Stool studies for ova, cyst, parasites and clostridium difficile were negative. Indian ink staining of stool sample had no evidence of Cryptococcosis. Serum PCR for cytomegalovirus was also negative. CT abdomen showed normal visualized bowel and other viscera. Upper GI endoscopy was unremarkable. Colonoscopy revealed multiple small ulcers with erythematous hue and clean base particularly in ceacum and along ascending colon. Multiple colonic biopsies were taken. Histopathology showed lymphoplasmacytic infilterate in the lamina propria. It also showed increased presence of foamy histiocytes, several of which also showed interacellular organism bearing a pseudocapsule. PAS stain also confirmed budding of these interacellular organisms which is consistent with Histoplasmosis. His HRCT chest revealed hyperinflated lungs, cylindrical bronchiectasis in left upper lobe. Urine for histoplasma antigenuria was negative. Result(s): He was treated with intravenous liposomal amphotericin B for initial two weeks followed by oral itraconazole. His symptoms responded remarkably to the treatment. In view of persisting thrombocytopenia and histoplasmosis his mycophenolate was stopped and tacrolimus was titrated as per trough levels Conclusion(s): Colonic histoplasmosis is associated with significant mortatlity and morbidity. Prolonged use of immunosuprresants, use of antirejection therapies (like high dose pulse methyl prednisolone and bortezomib) and even in some case reports COVID 19 infection have shown to increase the risk of histoplasmosis. Primary and isolated colonic histoplasmosis like in this case can be the atypical presentation which emphasizes the importance of maintaining a low threshold for consideration of histoplasmosis in renal allograft recipients. No conflict of interestCopyright © 2023

Clinical Profile and Outcomes of Covid-19 in Renal Transplant Recipients - a Single Centre Experience

Introduction: The COVID-19 infection amongst the renal transplant recipients (RTR) has a varied presentation and severity of illness. The overall mortality amongst RTR was found to be 11.6%- 27% compared to the mortality rate of 2-3% amongst the COVID-19 infected general population. The incidence of acute kidney injury(AKI) in RTR was also found to be higher compared to general population with Covid 19 (27.5% versus 13.3%). We assessed the clinical outcomes of COVID 19 infection among RTR and its impact on the graft function along with predictors of poor clinical outcomes. Method(s): Ours is a single centre observational cohort study of 83 RTR with Covid 19 infection with a follow up period of 6 months. The data pertaining to demographics, renal transplantation, maintenance immunosuppression, baseline allograft function prior to Covid 19 infection and comorbidities was recorded in both hospitalised and outpatient RTR. Lab investigations including renal function tests and inflammatory markers were noted. Renal allograft function was assessed by estimated glomerular filtration rate(eGFR) using CKD-EPI equation prior to admission, hospital stay and 6 months follow up. The need for oxygenation, invasive ventilation;presence of hypotension, acute kidney injury(AKI),acute respiratory distress syndrome(ARDS) and need for renal replacement therapy(RRT) was noted. Modification of immunosuppressant medications with respect to dose reductions and withdrawal was recorded. The primary endpoint was mortality and presence of acute kidney injury during Covid 19 infection. Result(s): The mean age was 47.67+/-13.7 years and 75.91 % were males. Around 81.9%(68/83) RTR were hospitalised & 18.9%(15/83)were managed as outpatients. Out of 83 patients,43 (51.8%), 23(27.7%),17(20.5%) had mild, moderate and severe COVID 19 illness respectively. The mortality rate amongst COVID 19 infected RTR was 19.3%(16/83). Out of 83 RTR,17 required inotropic support owing to hypotension. The baseline eGFR(ml/min) prior to Covid 19 infection was 66.3 +/- 30.66. The eGFR(ml/min) during Covid 19 was 44.27 +/- 31.53.Acute kidney injury(AKI) was seen in 72.3%(60/83) of RTR.19.28%(16/83) required RRT.The percentage change in eGFR from baseline during COVID-19 was found to be statistically significant(p=0.003)and correlated with mortality(p=0.003).At 6 months of follow up,55/83 RTR had stable allograft function with mean eGFR(ml/min) of 51.74 +/- 29.92 and 8/83 patients(9.6%) patients were on maintenance haemodialysis. In contrast to the survivors, the non survivors had a higher mean age(67+/-13 vs 57+/-12 years), number of years of hypertension(15+/-9 vs 8.5 +/-7 years),body mass index(27.05+/-4.7 vs 23.11+/- 7.8), percentage change in eGFR from baseline(114.1 +/-81.7% vs 58.8 +/-61.4%), serum Interleukin levels (120.7 vs 10 pg/ml) and D dimer(145 vs 21.3 mcg/ml) levels (p<0.05).Other risk factors which correlated significantly with outcome of mortality and reduced renal recovery include presence of hypoxia at presentation and ARDS(87.5 Vs 28.1%),presence of hypotension requiring inotropes(81.3% vs 6%) and AKI and the need for RRT(56.7% vs 10.4%). [Formula presented] [Formula presented] Conclusion(s): The mortality rate amongst the RTR with COVID 19 infection was found to be 19.3%.AKI was found in 72% of patients during the illness and about 9.6% developed graft loss by 6 months. RTR needs a close supervision and follow up as they are prone to acute kidney injury and may develop allograft failure. No conflict of interestCopyright © 2023

COVID-19 in kidney transplant recipients.

There is minimal information on coronavirus disease 2019 (COVID-19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47-67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID-19 testing was 2822 days (IQR 1272-4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X-ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID-19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals.

A CASE OF LONG-TERM TOLERANCE AFTER KIDNEY TRANSPLANTATION.

We present a case of long-term organ functioning (ca.10 years) after allografting of a cadaveric kidney without usage of immunosuppressing drugs. In 2005, a patient suffering from a hypertensive form of chronic glomerulonephritis, have received an allogeneic graft of cadaveric kidney compatible for AB0 system, HLA antigens (A19, B07, DR04), and negative results of cross-match test. The graft function was immediately restored, with normalization of creatinine levels achieved 4-5 days after surgery. Immunosuppression with cyclosporine, solumedrol, cellcept, metypred and simulect was performed in the hospital. Pulse therapy with solumedrol was performed on the day +20 due to the development of initial rejection signs. The postoperative period proceeded without infectious complications. The patient was discharged being recommended to take cyclosporine, Cell-Sept and Metypred. Within a year after transplantation, the patient claimed for pain in the hip joint, and, therefore, metypred was completely canceled. Subsequently, the Cellcept was replaced with a Mayfortic. In 2007, the signs of coxarthrosis were revealed at computed tomography, followed by aseptic necrosis of the the right femur head. Deforming osteoarthritis of the right hip joint was detected, and the hip replacement surgery was suggested. In 2010, due to risk of side effects from ongoing immunosuppressive therapy, e.g., joint damage, the Mayfortic was canceled. In 2012, being in fear of original Sandimmun Neoral replacement by a generic drug, the patient completely refused cyclosporine therapy. In 2021, the endoprosthetics of the right hip joint was performed, and the surgical wound healed initially. Since 2012, the patient has not completely taken immunosuppressive therapy. Over this time period, the patient has never been admitted to the hospital for impaired functioning of the organ graft. Meanwhile, he monitored his graft function on regular basis undergoing biochemical analyses, clinical examination, ultrasound studies of the graft and made regular visits to the outpatient department. In 2021, a week after hip replacement, there was a slight increase in serum creatinine, followed by further increase to 230 mmol/L in 2021, and to 310 mmol/L in March 2022. In February 2022, the patient suffered mild respiratory infection (confirmed COVID-19). In March 2022, the first clinical signs of increasing nephropathy appeared, i.e., swelling of both lower extremities, with leukocytes in urine upon routine analysis, increased blood flow resistance in the main artery of the transplant shown by ultrasound study. Due to worsening of the patient's condition, he resumed taking the prescribed immunosuppressants. Copyright © 2022, SPb RAACI.

Viral reactivation after hcv-positive renal allograft transplantation

Case Report: A 48y/o man with a history of ESRD secondary to FSGS was found to have hepatitis-C virus (HCV) reactivation after kidney transplantation (KT) with an HCV-positive allograft. The patient was HCV-negative before transplantation in July 2021. He was negative for hepatitis-B virus (HBV) core antibodies but had evidence of prior HBV vaccination and was negative for HIV 1/2. His induction therapy included thymoglobulin, and his maintenance immunosuppressive regimen included mycophenolate mofetil (MMF), tacrolimus, and prednisone. Aweek after KT, the patient tested positive for HCV genotype 1a, and he was started on sofosbuvir/velpatasvir in August 2021. Lab monitoring showed decreasing levels of HCV viral load (VL) until it was undetectable 2 months later. In January 2022, renal function remained stable, and urinalysis and hepatic function tests remained unremarkable. However, HCV viral load was positive in February 2022 and the HCV genotypewas 1a, as before. This result raised the possibility of reactivation of HCV from his allograft more than 6 months post KT. Additionally, despite negative BK polyoma VL initially, he was positive in January 2022 and discontinued his MMF. He was also positive for COVID-19 in January 2022 as well. Given his recurrence of HCV VL, he initiated sofosbuvir/velpatasvir/ voxilaprevir in April 2022 and completed therapy in July 2022, and maintained sustained viral response (SVR) as of October 2022. His BK VL was negative in May 2022. Recent guidelines on preventing HCV reactivation in allograft-positive KT recipients state that individuals should achieve SVR after 8-12 weeks of a course of direct-acting antiviral (DAA) therapy. The patient completed DAA therapy post-transplantation with a successful negative viral load 2 months later. However, he did not achieve SVR because his VL was again positive 3 months after completion of therapy. Reactivation of BKV, a DNA virus that establishes lifelong infection in renal tubular and uroepithelial cells, is common among KT recipients, but there is insufficient evidence to establish a causal association between BKV reactivation and HCV reactivation. There is no consensus on a chemotherapeutic maintenance regimen to prevent HCV reactivation. This case highlights the importance of close follow-up monitoring for HCV and BKV among KT recipients and the need to explore the relationship between BKV reactivation, HCV reactivation, and immunosuppression regimen. Copyright © 2023 Southern Society for Clinical Investigation.

Covid and Kidney-Oea Friend or Foe

BACKGROUND: Covid-19 has been associated with worsened prognosis in patients with kidney involvement. The incidence of acute kidney injury (AKI) in Coronavirus-19 disease (COVID-19) patients ranges from 0.5% to 35%. AIM OF THE STUDY: We evaluated the prevalence severity risk factors and prognosis in patients with COVID-19 having AKI or CKD. METHOD(S): We conducted a retrospective analysis of 70 patients with Covid-19 presenting to nephrology department. Outcome of patients with CKD stage 1-2 was compared with that of patients with AKI kidney transplant and CKD stage G3a-G5D. RESULT(S): In this study, 15 (21.4%) patients had CKD stage G1-2, 18 (25.71%) had CKD stage G3a-5c and 11 (15.7%) had CKD stage G5d. Eight patients (11.4%) were with functioning renal allograft (CKD-T). Four (5.71%) developed AKI and 14 patients (20%) had acute on CKD. Overall;in-hospital mortality was 27.14% (n = 19). Of these, 3 patients (15.78%) had CKD stage G1-G2, 7 (36.84%) had CKD stage G3a-5c, 3 had CKD G5D, 2 (10.55%) had acute on CKD, one had AKI and 3 patients had a functioning kidney allograft. Baseline & nadir serum creatinine & eGFR of CKD stage 1-2, CKD Stage 3a-5c and stage CKD-t was 0.87 (eGFR 82), 7.34 (eGFR 11.61), 3.24 (eGFR-24.86);and 0.74 (eGFR 93.55), 5.37 (eGFR 16.55) and 1.85 (eGFR 42.28) respectively. CONCLUSION(S): A rather low prevalence of AKI in our Covid-19 patients, lower mortality in acute on CKD patients & improvement in eGFR in CKD & transplant patient in our study suggest that coronavirus has minimal, if any direct toxic effect on kidney. But presence of renal failure worsens the outcome of Covid-19 disease.

Association of Human Leucocyte Antigens with Anti-Sars-Cov-2 Spike Protein Antibody Formation in Response to Vaccination in Renal Allograft Recipient

BACKGROUND: Cellular and humoral response are required for SARS-CoV-2 eradication. Antigen-presenting cell loads SARS-CoV-2 peptides on human leukocyte antigen with different avidity and present to T and B cell for humoral and cellular activity. Due to immunosuppression, renal transplant recipient patients are speculated to poorly form the antibody against SARS-CoV-2 virus. Therefore, determining the association of specific HLA alleles with anti-SARS-CoV-2 spike protein antibody formation will be helpful in managing the renal transplant recipient patients having specific HLA alleles from SARS-CoV-2 infection and vaccination. AIM OF THE STUDY: To study the association of human leukocyte antigens with anti-SARS-CoV-2 spike protein antibody formation in response to vaccination in renal allograft recipient METHODS: In this study, anti-SARS-CoV-2 spike protein antibody in 78 renal allograft recipient patients were determined by the chemiluminescent microparticle immunoassay methods and human leukocyte antigen alleles were determined by the polymerase chain reaction-single strand oligonucleotide methods and analyzed to study the association of human leukocyte antigens with anti-SARS-CoV-2 spike protein antibody formation in response to vaccination in renal allograft recipient RESULTS: The mean age of the patients in seroconversion vs non-seroconversion (45.88 +/- 8.86 vs 45.55 +/- 8.74, p value - 0.90). The post-transplant interval in seroconversion vs non-seroconversion (103.63 +/- 57.57 vs 77.45 +/- 35.25, p value - 0.14). The duration between the vaccination with both the doses and sample collection of renal transplant recipients in seroconversion vs non- seroconversion (47.58 +/- 30.18 vs 45.55 +/- 35, p value - 0.85). The anti-SARS-CoV-2 spike protein antibody seroconversion rate in renal allograft recipients were 85.9% with median titer in seroconversion vs non- seroconversion 3175.00 (IQR, 798.50 - 8391.70) vs 5.50 (IQR, 4.10 - 8.20, p value - 0.001). In covishield vs covaxin group 2500.70 (IQR, 146.40 - 7705.60) vs 1828.70 (IQR, 665.00 - 3765.10, p value - 0.63). The frequency of HLA class I alleles A*26 was 18.18%, B*08 was 18.18%, C*05 was 25% and Class II HLA alleles - DRB1*03 was 18.18%, and HLADQA1* 20 was 25% of patient were significantly associated with non-seroconversion and C*06 was 18.75% were significantly associated with seroconversion. CONCLUSION(S): Renal transplant recipients with anti-SARSCoV- 2 vaccination developed a robust seroconversion rate of 85.9% and alleles of A*26, B*08, C*05, DRB1*03, and DQA1*20 were significantly associated with non-seroconversion.

Impact of the COVID-19 Pandemic on Molecular Surveillance in the KOAR Registry

Background: The SARS-CoV2 pandemic increased the complexity of delivering clinical care and laboratory services for immunosuppressed kidney transplant (KTx) recipients. We evaluated how the pandemic impacted adherence with laboratory draws among patients in the Kidney allograft Outcomes AlloSure Registry (KOAR,NCT03326076). Method(s): 1663 KTx recipients undergoing post-transplant surveillance using donorderived cell-free DNA (dd-cfDNA) were enrolled in KOAR between 2017 and 2021. Participating centers were free to individualize their surveillance strategies. We estimated adherence by using the pre-pandemic distribution of surveillance dd-cfDNA draws across participating sites to establish a baseline regimen, and then compared adherence before the pandemic (P1;through 1/2020) with two subsequent periods in 2020: P2 (2/2020 - 6/2020), coinciding with the first wave of infections, and P3(7/2020 - 12/2020), which captures the bulk of the second and third waves in the US. Result(s): The distribution of surveillance dd-cfDNA draws at participating sites before COVID (P1) identified 7 peaks corresponding to draw points at months 1, 2, 3, 4, 6, 9, and 12 [Figure 1a]. Estimated adherence during P1 based on this regimen was 60.5%. Over the subsequent 5 months (P2), reflecting the early months of the pandemic, adherence declined to 50.5% (p < 0.01). After the expanded availability of mobile phlebotomy services in 7/2020 and despite rising SARS-CoV2 case counts and hospitalizations, adherence during P3 improved to 57.6% (p < 0.01 compared to P2, p = 0.1 compared to P1) [Figure 1b]. Conclusion(s): Our findings demonstrate that adherence to laboratory surveillance among transplant recipients enrolled in the KOAR registry declined in theearly period of the SARS-CoV2 pandemic, however, a variety of adaptations in the latter half of 2020, including the widespread availability of remote phlebotomy for these patients, appears to have led to substantial improvements, with adherence approaching pre-pandemic levels. (Figure Presented).

Impact of ATG Dose Reduction on Kidney Transplant Outcomes During the Covid-19 Pandemic

Purpose: During the COVID-19 pandemic, many transplant centers modified induction immunosuppression regimens. Beginning December 2020, our center reduced anti-thymocyte globulin (ATG) protocol dosing by up to 33% compared to the pre-pandemic doses (7.5, 4.5, and 3mg/kg, per immunologic risk) for all recipients, with no change in maintenance immunosuppression. We examined the impact of reduced ATG dose on kidney allograft and transplant recipient outcomes. Method(s): We retrospectively reviewed adult recipients who received a kidney transplant between December 2020 and March 2021 (pandemic) with a minimum of 6 months follow up post-transplant, and recipients who received a transplant between January 2019 and December 2019 (pre-pandemic). We chose 2019 as a comparable pre-pandemic cohort as they were treated without influence from the COVID-19 pandemic. We ed patient demographic and laboratory data from electronic health records. We excluded multi-organ transplant recipients. Result(s): 78 adult kidney transplants were performed during the pandemic era and 211 were performed during the pre-pandemic era. The characteristics of the two cohorts are illustrated in Table 1. The primary outcomes are illustrated in Figure 1. The rate of biopsy proven rejection (including surveillance and for-cause biopsies) did not increase during the pandemic as compared to pre-pandemic era (6.3% vs 8.0%, respectively, p=0.8). The rate of BK viremia (>1000 copies/mL) at 3 months was lower in the pandemic era, but not statistically significant (6.4% vs 8.7%, respectively, p=0.6). The rate of delayed graft function (DGF) was significantly higher in the pandemic era compared to pre-pandemic (42.3% vs 22.9%, respectively, p=0.002). No recipients tested positive for COVID-19 within 1-month of transplant. Conclusion(s): Despite the reduction in ATG dose, we found no significant change in the rate of rejection or infection. We did however find a significant increase in the rate of DGF during the pandemic era. Further studies are needed to assess the long-term effects of reduced induction immunosuppression regimen on kidney transplant recipients. (Figure Presented).

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.

Kidney Transplantation from Covid-19 Deceased Donors

Purpose: Transplant volumes decreased significantly during the first months of global pandemic of COVID-19, followed by a shift in the standard of care of transplant medicine. It has become widely accepted to rigorously screen and test donors and recipients for COVID-19 before proceeding with transplant. Discarded kidneys due to positive COVID-19 testing in potential donors is a new challenge for transplant centers. The emerging vaccines and lines of therapy have given us tools that could be utilized to re-balance the shift in practice and maximize organ utilization. Method(s): In this we present two cases of kidney transplantation from a COVID-19 positive deceased donor. The first recipient was a 40-year-old female who has been vaccinated with two doses of mRNA-1273 vaccine five months before transplant. The second patient was a 41-year-old male without a prior COVID-19 vaccine, he had a natural infection with COVID-19 about 10 months prior to transplant, and antibody was positive for anti-nucleocapsid IgG at the time of transplantation. Both recipients had negative SARS-CoV-2 nasopharyngeal swab PCRs prior to transplantation, and both received induction with anti-thymocyte globulin 5mg/ kg. Both recipients received their transplanted kidneys from the same donor, who tested positive by RT-PCR for COVID-19 from a nasopharyngeal swab three days prior to procurement (Roche Cobas Liat PCR, single cycle threshold). On the following day, the donor's bronchial washing was negative. At the day of procure662 Kidney Deceased Donor Selection ment, repeated PCR from a nasopharyngeal swab was negative, and COVID-19 antibody was positive for anti-nucleocapsid IgG (AbbottTM ARCHITECTTM). The donor cause of death was head trauma with a terminal serum creatinine of 0.3mg /dL Chest imaging did not demonstrate COVID-19 pneumonitis. Casirivimab 600mg and imdevimab 600mg were administered 24 hours after the last dose of anti-thymocyte globulin as post-exposure prophylaxis. Result(s): Both recipients had an appropriate renal allograft function. Casirivimab 600mg and imdevimab 600mg were administered 24 hours after the last dose of anti-thymocyte globulin. Both recipients demonstrated no signs or symptoms of COVID-19 infection during their hospitalization and were instructed to maintain 14 days of COVID-19 exposure precautions post-discharge. At 12 weeks from transplant, both patients had no symptoms of COVID-19 infection. SARS-CoV-2 RNA has been detected in several organs including kidney, but there was no proof of infective virus in extrapulmonary organs. Conclusion(s): These two cases may broaden the scope of accepting organs from COVID-19 positive deceased donors and the use of casirivimab and imdevimab for immediate post-transplant surgery prophylaxis. While we are not sure if the monoclonal antibodies did offer any benefits here, we think that this report may throw the light on its potential use in post-transplant surgery prophylaxis. Further studies are warranted to examine the benefits of such practice.

Impact of the Covid-19 Pandemic on Longitudinal Molecular Surveillance in the KOAR Registry

Purpose: The SARS-CoV2 pandemic increased the complexity of delivering routine clinical care and laboratory services for immunosuppressed kidney transplant (KTx) recipients. We evaluated how the pandemic impacted adherence with scheduled laboratory draws among patients enrolled in the Kidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076). Method(s): 1663 kidney transplant (KTx) recipients undergoing post-transplant surveillance using donor-derived cell-free DNA (dd-cfDNA, AlloSure, CareDx Inc.) were enrolled in KOAR between 2017 and 2021. Participating centers were free to individualize their surveillance strategies. We estimated adherence by using the pre-pandemic distribution of surveillance dd-cfDNA draws across participating sites to establish a baseline regimen, and then compared adherence before the pandemic (P1;through 1/2020) with two subsequent periods in 2020: P2 (2/2020 - 6/2020), coinciding with the first wave of infections, and P3 (7/2020 - 12/2020), which captures the bulk of the second and third waves in the US. Result(s): The distribution of surveillance dd-cfDNA draws at participating sites before COVID (P1) identified 7 peaks corresponding to draw points at or around months 1, 2, 3, 4, 6, 9, and 12 [Figure 1a]. Estimated adherence during P1 based on this regimen was 60.5%. Over the subsequent 5 months (P2), reflecting the early months of the pandemic, adherence declined to 50.5% (p < 0.01). After the expanded availability of mobile phlebotomy services in 7/2020 and despite rising SARS-CoV2 case counts and hospitalizations, adherence during P3 improved to 57.6% (p < 0.01 compared to P2, p = 0.1 compared to P1) [Figure 1b]. Conclusion(s): Our findings demonstrate that adherence to laboratory surveillance among transplant recipients enrolled in the KOAR registry declined in the early period of the SARS-CoV2 pandemic, however, a variety of adaptations in the latter half of 2020, including the widespread availability of remote phlebotomy for these patients, appears to have led to substantial improvements, with adherence approaching pre-pandemic levels.

Role of Urinary Biomarkers in RWE Clinical Paradigm

Purpose: Due to heterogeneity observed in the kidney transplant population, it has been extremely challenging for traditional methods such as histopathology to predict graft outcomes. In this real-world evidence(RWE) study, we applied machine learning (ML) models to a multi-analyte urinary biomarker assay to predict whether a kidney allograft would experience a rejection episode. Method(s): A cohort of 550 (37.5% biopsy matched) urine samples from patients across 3 renal transplant centers were used to develop a predictive ML model (scaled 0-100) to prognosticate allograft failure. Samples were collected between 1-1539 days post-transplant from allograft recipients with ages ranging from 7-77 years. Of the 206 biopsy matched samples, acute kidney allograft rejection (AR) and no-rejection (NR) phenotypes were confirmed in 136 and 70 respectively. We also evaluated the developed ML model on two additional cohorts of 15 COVID+ transplant recipients and 30 non-transplant healthy population. The ML model incorporates clinico-demographics with 6 urinary biomarkers: Clusterin, total protein, CXCL10, Creatinine, cfDNA and methylated cfDNA. Monte Carlo confidence intervals for the model incorporated biomarker assay and sample variances. Result(s): The novel rejection score was able to discriminate AR from NR efficiently. Score below 32 classified stable allograft, score range of 32 - 55 identified progression of AR, and Score > 55 identified AR with high sensitivity: 92%, and specificity: 89%;AUC: 96% and accuracy: 91%(figure). The associated NPV and PPV of 87% and 93% respectively. In the COVID cohort with 86% clinician assessed rejection, the median score was 51(IQR:30-87). In the non-transplants the median score was 19(IQR:13-26). It was established that presence of COVID was not a confounder in the model. Conclusion(s): The accuracy of the novel rejection score emphasizes the promise of applying ML algorithms as an aid to decision-making in evaluating graft outcomes with high sensitivity and specificity. Moreover, this RWE retrospective analysis demonstrates the efficacy of the urine multi-analyte approach to accurately predict acute rejection in kidney transplant recipients. (Figure Presented).

Assessment of Humoral and Cellular Immune Responses to Sars Cov- 2 Vaccination in Immunocompromised Renal Allograft Recipients

Purpose: SARS CoV-2 vaccination elicits both robust humoral and T-cell immune responses in healthy individuals. However, a comprehensive assessment of immune responses to SARS-CoV-2 vaccination in renal allograft recipients is variable and dependent primarily on Spike IgG levels. Here, we analyzed the humoral and T-cell responses in vaccinated transplant recipients. Method(s): 61Tx patients maintained either on Tacrolimus (TAC, 32) or Belatacept (BELA, 29) who were greater than one month post 2nd dose of the Pfizer BNT162b2, and 41 healthy individuals were enrolled. Fresh whole blood was incubated with SARS CoV-2 Spike peptides pool and the activated CD4+ (IL-2/TNF-alpha)+ and CD8+ (TNF-alpha/IFN-gamma)+ T cells were enumerated by flow cytometry and defined as CoV-2-specific T cells. Plasma was analyzed for Spike Receptor Binding Domain (RBD)-specific IgG by ELISA. The Spike RBD-specific IgG levels and Spikespecific CD4+/CD8+ T-cell immune responses were analyzed in TAC- and Bela- Tx patients along with healthy controls. Result(s): Our data demonstrated poor Spike IgG and T cell immune responses in Tx patients1M post-2nd dose of vaccine (21% v. 93% in positive Spike IgG and 37% v. 88% in positive T cell responses, Tx v. controls, respectively). However, 34% of Spike IgG (-) patients demonstrated positive CD4+ and/or CD8+ T-cell immune responses. No significant difference in T cell immunity was found between TAC and BELA treated patients. Conclusion(s): Immunocompromised Tx patients demonstrated significant defects in humoral and T cell immune response after vaccination. Patients maintained on TAC v. BELA demonstrated similar depressions in immune responses post-vaccination. 34% of vaccinated Tx patients, demonstrated Spike-specific T cell immunity despite being Spike IgG negative. This is suggestive of a divergent immune response with dominant cellular immunity. These observations are important since activation of T-cell immunity early after exposure to SARS-CoV2, while not preventing infection will likely modify severity of disease. (Table Presented).

Abnormal B Cell Profile Associated with Inadequate Antibody Response to MRNA SARS-COV-2 Vaccine Can Be Overcome with a Third Vaccine Dose in Adolescent Kidney Transplant Recipients. C. Crane

Purpose: mRNA SARS-CoV-2 vaccines are highly efficacious in the general population but have shown a diminished response in immunosuppressed adolescent kidney allograft recipients. We investigated immunological parameters that could be associated with a blunted antibody response. We also analyzed whether a third vaccine dose could improve the antibody response. Method(s): Adolescent kidney transplant recipients who received mRNA SARSCoV- 2 vaccine had SARS-CoV-2 spike protein antibody levels measured 4-8 weeks after their second vaccine dose and again after the third vaccine dose. Immunological labs including lymphocyte subsets, immunoglobulin levels, and vaccine titers and immunosuppressive medication dosing were evaluated prior to vaccination. Patients were compared in groups of vaccine responders vs non-responders via a Mann-Whitney U test. The impact of mycophenolate mofetil dosage on immune parameters was analyzed via a linear regression model. Result(s): 14 of 27 (52%) vaccinated pts had a positive spike antibody level. There was no significant difference in immunoglobulin levels, T-cell populations, or vaccine titers. There was a trend toward negative spike antibodies with higher doses of mycophenolate mofetil, MMF, at 91 mg/m2/day median difference (p=0.06). All four patients receiving azathioprine instead of MMF developed spike antibodies. Non-responders had lower hemoglobin levels (beta=-1.30, p=0.009) and lower platelet count (beta=-56.00, p=0.057). MCV levels were normal in both groups. Non-responders showed a trend toward increased naive B-cell percentage (beta= 12.50, p=0.11) and decreased total memory B-cell percentage (beta=-12.54, p=0.080). Increasing MMF dosage was associated with an increase in naive B-cell percentage (beta=0.016, p=0.0032) decrease in total memory B-cell percentage (beta=-0.016, p=0.0034), and decreased in IgG level (beta=-0.35, p=0.012). Of the 13 patients that did not develop spike antibodies after the second vaccine dose, 9 pts (69%) developed antibodies after the third dose. In total, 23/27 (85%) patients vaccinated developed spiked antibodies. Conclusion(s): Disruption in B-cell population could be due to immunosuppression with MMF. Non-responders showed trends toward high MMF dosage, increased naive B-cell percentage, and decreased total memory B-cell percentage. Increasing MMF dosage was associated with all trends as well as decreased IgG levels. Decreased hemoglobin levels and normal MCV supports that anemia could be due to bone marrow suppression caused by MMF. Altered B-cell populations and MMF therapy are a potential biomarker for reduced efficacy of SARS-CoV-2 vaccine in adolescent kidney allograft recipients. Interestingly, a third vaccine dose can overcome the immunosuppressive effects and improve vaccine efficacy.