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

Successful Kidney Transplantation from Covid-19 Positive Donors

Introduction: Covid-19 results in a wide spectrum of illness ranging from asymptomatic, mild to severe respiratory disease and multi-organ involvement. Transplant recipients are at increased risk of severe Covid-19. The risk of transmission from a Covid-19 positive donor to recipient in kidney transplantation is unknown. National Health Service Blood and Transplant, UK recommended respiratory polymerase chain reaction (PCR) testing for all donors for Covid-19 and advice against organ donation if positive within the last 28 days. However, a recent amendment of guideline (www.odt.nhs.uk, POL304/3) supports organ donation from selected donors with positive or indeterminate SARS-CoV-2 PCR results. Method(s): We report two cases of kidney transplantation including one unvaccinated recipient where donors had tested SARS-CoV-2 PCR positive. Result(s): 1: Mrs A is a 38-year old Caucasian with end-stage kidney disease (ESKD) secondary to reflux nephropathy, established on haemodialysis (HD). She had declined Covid-19 vaccinations. The donor died of traumatic brain injury and he had a positive lateral flow test 3 weeks prior. The PCR test was positive. Decision was made to proceed with deceased donor kidney transplantation. She was high immunological risk with a HLA antibody calculated reaction frequency (CRF) of 79%, donor specific antibody negative. She was given Basiliximab induction followed by Tacrolimus, Mycophenolate Mofetil and steroids. Graft function was immediate and at 3 week post-transplant, she is well with excellent graft function and no evidence of Covid-19. 2: Mrs B is a 63-year old Asian with ESKD secondary to diabetes and hypertension. She was established on HD and fully vaccinated (three doses of Pfizer-BNT162b2 mRNA vaccine). The donor died of subarchnoid haemorrhage. He had a positive lateral flow test 15 days prior with flu-like symptoms. Respiratory PCR for SARS-CoV-2 was positive. The decision was to proceed with deceased donor transplantation. She was low immunological risk with a HLA antibody CRF of 0%. There were no peri-operative complications and she had immediate graft function. She had Basiliximab induction and was discharged on Tacrolimus and Mycophenolate mofetil with prednisolone withdrawn on day 7 (our low immunological risk protocol). At 3 week post-transplant, she is well with no evidence of Covid-19 and excellent graft function. Conclusion(s): We report 2 cases of kidney transplantation from Covid-19 positive donors in whom the cause of death was not Covid-19 pneumonia. Covid-19 status of the donor was discussed with the patients who both consented. Neither recipient developed Covid-19 in the early post-transplant period, despite being heavily immunosuppressed. Although there remains a theoretical risk, there are no reports of transmission of Covid-19 to kidney transplant recipients from positive donors. Prophylactic antivirals or monoclonal antibodies for the recipient post-transplant or spike antibody test to guide decision making are not currently recommended. We used clinical details of the donor and virology advice which accounts for PCR cycle threshold value to make a decision to transplant. The outcomes of 2 patients reported along with similar experience from other centres is encouraging and supports use of kidneys from selected SARS-CoV-2 positive deceased donors after obtaining virological advice and appropriate consent. No conflict of interestCopyright © 2023

Single Center Comparative Analysis of Abo Compatible Versus Abo Incompatible Kidney Transplant with Short Term 1 Year Follow Up

Introduction: Kidney transplantation is the best treatment option for patients with end-stage kidney diseases. Quality and longevity of life are better with kidney transplant than chronic dialysis. Kidney paired donation and ABO incompatible kidney transplant (ABOiKT) are among the strategies to expand the living donor pool to overcome shortage of organs. Although first ABOiKT done in 1951 by Hume et al. was an unsuccessful attempt;Alexander et al. in 1987, proposed desensitization protocol with successful ABOiKT. Advancements in desensitization protocols have resulted in increasing success with ABOiKT. In developing countries like India, numbers of ABOiKT are steadily increasing. Aim of this study was to assess short term outcome of ABOiKT and their comparison with ABO compatible kidney transplant (ABOcKT). Method(s): This was a single center prospective observational study done over a period of 2 years. All the living donor kidney transplants including both ABOcKT and ABOiKT done between September 2020 to August 2021 at Jaslok Hospital and Research Center, Mumbai were included in this study. All ABOiKT recipients underwent pre-transplantation desensitization with injection rituximab and plasmapheresis. Pretransplant isoagglutinin titer of <= 1 : 8 was considered acceptable. Inj. Antithymocyte globulin (ATG) (1mg/kg), Inj. Anti-T lymphocyte globulin (ATLG) (3 to 5 mg/kg) or Inj. Basiliximab (20mg 2 doses 4 days apart) was used as induction agent. Triple immunosuppression regimen of prednisolone, tacrolimus and mycofenolate mofetil was started 7 days prior to transplant in ABOiKT and 2 days prior to transplant in ABOcKT and continued in post-transplant period. Valganciclovir was given to all patients for Cytomegalovirus (CMV) infection prophylaxis for 6 months. All the transplant recipients were followed up at 0, 3, 6, 9 and 12 months after transplant and in between when clinically indicated. Data collected was analyzed at the end of 1 year for outcomes of rejection episodes, graft dysfunction, graft loss, infections and death. Result(s): Total 95 patients were included in study, 29 (30.5%) out of them were ABOiKT recipients. Mean (SD) age of study population was 37.8 (+/- 10.5) years. Blood group B to B was the most common ABOcKT and B to O was the most common ABOiKT. Highest baseline isoagglutinin titer was 1:1024.There was no significant difference for rejection episodes, graft dysfunction, graft loss and death in ABOiKT and ABOcKT groups. Urinary tract infection was the most common infection in post-transplant period. COVID-19 was most common viral infection followed by CMV infection. Bacterial infections and overall infections were significantly higher in ABOiKT recipients (p value 0.001 and 0.006 respectively) but severe infections requiring hospitalizations and ICU care were not significantly higher. Two deaths occurred during our study, one in each group. One death was related to COVID-19 infection and second was because of pulmonary mucormycosis. Conclusion(s): Contrary to belief, ABOiKT has non inferior short term outcomes when compared with ABOcKT. Though in our study, bacterial infections were significantly higher in ABOiKT recipients, severe infections requiring hospitalization and ICU care were not increased. ABO incompatible kidney transplantation is an effective modality to increase donor pool and can be applied more widely. No conflict of interestCopyright © 2023

A Single Centre Experience of Post Renal Transplant Infections in a Tertiary Care Centre in Eastern India

Introduction: In developing countries, Post renal-transplant infections is the leading cause of mortality, morbidity and decreased allograft survival. Our aims and objectives was to determine the incidence and prevalence patterns of clinically or microbiologically confirmed infection in the post renal transplant patients of our population and profiling of infections in relation to time period from the Transplant and the induction agent, also to develop strategies to counter risk of post transplant infection. Method(s): This was a retrospective observational study. Time period: January 2020- April 2022. Post renal transplant recipients presenting with infections (with informed consent) was enrolled in this study. Recurrent episodes of infection by different organisms in a same patient treated as a separate event. Data was tabulated using MS excel and all results projected in bar graphs, pie charts, histograms. Differences of quantitative parameters between groups were assessed using the t test(for data that were normally distributed) or nonparametric test (for data that were not normally distributed). Differences of qualitative results were compared using chi2 test. Kaplan-meier was used for survival analysis. P < 0.05 was considered significant. Result(s): 213 incidents of post renal transplant infections were documented in 148 patients between the study period. Of the 85 patients who underwent renal transplant(57 living donor and 28 cadaveric) in this time period 33(38.8%) patients presented with 42 incidents of infections. Majority (74.3%) : Males. Mean age: 36.3+/-5.6 years. Most common cause of native kidney disease was chronic glomerulonephritis(30%). 121 (81.7%) had living donor transplant and 27(8.3%) patients had cadaveric transplant. Induction agent was basiliximab in 97 patients (65.5%) had 133 infections (62.4%) and ATG was used in 51 patients (34.5%) had 80(37.6%) infections. In recent transplant (last 2 yrs) cases-In Basiliximab group: infection rate 4.1 in 100 patient months and in ATG group infection rate was 5.7 in 100 patient months. (p=0.28). 37.5%cases had infections with graft dysfunction most commonly AKI. Immediate post transplant infections (<1 month) were 34 (15.9%), most commonly UTI (44.11%) followed by pneumonia (15.9%). 48(%) infections occurred between 1-6 months, most commonly pneumonia(27.08%) followed by UTI(22.9%) and superficial fungal infection. Pulmonary tuberculosis was in 14 (6.6%) cases. 3 cases had disseminated TB. Infectious diarrhea was in 18(8.4%) cases, most common organism isolated was EAEC and EPEC. CMV colitis found in 3 cases. 27 (18.2%) patients had NODAT/PTDM. ParvoB19 was in 11(5.16%), CMV in 5 and BKVN in 3 cases. 41(19.2%) cases had severe sepsis requiring intensive care support. New baseline s.cr was achieved in 29.1% cases. Infection related death was 24(16.2%). COVID 19 infection was in 41 cases, 31.7% developed graft dysfunction and 18 (43.9%) required hospital admission due to moderate or severe disease. 2 patients had mucormycosis, one of them died after admission. [Formula presented] Conclusion(s): Profiling of infection in our centre is essential to formulate future strategies for infection control especially as the DDKT & ABOi KT is on the rise. Proper survillence, screening protocol, vaccination and patient education are essential to reduce the burden of post transplant infection and for better graft and patient survival. No conflict of interestCopyright © 2023

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.

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, cellсept, 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. © 2022, SPb RAACI.

Induction immunosuppression and outcome in kidney transplant recipients with early COVID-19 after transplantation.

Coronavirus disease 2019 (COVID-19) in kidney transplant recipients has a high risk of complications and mortality, especially in older recipients diagnosed during the early period after transplantation. Management of immunosuppression has been challenging during the pandemic. We investigated the impact of induction immunosuppression, either basiliximab or thymoglobulin, on the clinical evolution of kidney transplant recipients developing COVID-19 during the early period after transplantation. We included kidney transplant recipients with ˂6 months with a functioning graft diagnosed with COVID-19 from the initial pandemic outbreak (March 2020) until 31 July 2021 from different Spanish centres participating in a nationwide registry. A total of 127 patients from 17 Spanish centres developed COVID-19 during the first 6 months after transplantation; 73 (57.5%) received basiliximab and 54 (42.5%) thymoglobulin. Demographics were not different between groups but patients receiving thymoglobulin were more sensitized [calculated panel reactive antibodies (cPRAs) 32.7 ± 40.8% versus 5.6 ± 18.5%] and were more frequently retransplants (30% versus 4%). Recipients ˃65 years of age treated with thymoglobulin showed the highest rate of acute respiratory distress syndrome [64.7% versus 37.1% for older recipients receiving thymoglobulin and basiliximab (P < .05), respectively, and 23.7% and 18.9% for young recipients receiving basiliximab and thymoglobulin (P > .05)], respectively, and the poorest survival [mortality rate 64.7% and 42.9% for older recipients treated with thymoglobulin and basiliximab, respectively (P < .05) and 8.1% and 10.5% for young recipients treated with thymoglobulin and basiliximab (P > .05), respectively]. Older recipients treated with thymoglobulin showed the poorest survival in the Cox regression model adjusted for comorbidities. Thus thymoglobulin should be used with caution in older recipients during the present pandemic era.

Clinical Characteristics of Serologic Non-Responders to COVID-19 Booster Vaccination in a Cohort of Solid Organ Transplant Recipients

Purpose: The purpose of this study was to assess the clinical characteristics of serologic non-responders to COVID-19 booster vaccination in a cohort of solid organ transplant recipients. Method(s): All solid organ transplant recipients our center who received COVID-19 booster vaccination and had SARS-CoV-2 Spike IgG antibodies checked at least 4 weeks after the dose were included. We evaluated the patients who were found to have negative SARS-CoV-2 Spike IgG antibodies despite booster vaccination (i.e. serologic non-responders). Result(s): Among 657 solid organ transplant patients who had received a booster COVID-19 vaccination, 168 patients had Spike IgG antibodies checked during the study period. Forty-nine patients (29.2%) were found to be seronegative and were included in the analysis. 69% were male with a median age of 60 years. The majority of the cohort (47%) were kidney transplant recipients who had received primary vaccination series at a median of 206 days post-transplant. 65% had received basiliximab for induction immunosuppression. Most of the patients (65%) received primary vaccination with Pfizer COVID-19 vaccine and 67% received Pfizer COVID-19 booster vaccination at a median of 187 days after primary vaccination series. Spike IgG antibodies were checked at a median of 41 days from booster vaccination. No patients received rATG within 90 days of booster administration. Similarly, no patients received high dose (>250mg methylprednisolone equivalent) steroids within 30 days prior to booster vaccination. For immunosuppression, 27% were maintained on belatacept and 82% were on anti-metabolites at the time of the booster vacciantion. Ten patients (20%) experienced a COVID-19 infection postcompletion of their booster vaccination. Conclusion(s): In our solid organ transplant cohort, the majority of serologic nonresponders underwent basiliximab induction and were on an antimetabolite for maintenance immunosuppression. A limitation of our study was the use of different laboratory assays for determining IgG levels. Future work includes evaluating the clinical characteristics of COVID 19 booster serologic responders and comparing the two populations. (Table Presented).

COVID-19+ Kidney Transplant in US Veterans: An Opportunity to Increase Transplant Rates

Purpose: US veterans are less likely to be transplanted. This disparity is related to donor shortage. This study seeks to increase access to transplant of US veterans to transplants using covid+ organs. This provides high quality organs to underserved population, reduce discards and is safe. Report of safety of this strategy. Early reports demonstrates safety in using these organs. Method(s): Case presentation of two veterans transplanted with covid+ organs. Recipient and donor characteristics highlighted including vaccine status, antibody level (IgG) against Sars-CoV-2 prior to and following transplant. Organ function is reported and complications. Induction agent using non-depleting agent recorded. Informed consent obtained for covid+ organ. Infectious disease consultation. IgG antibody level check prior to transplant, and post transplant. Result(s): Two cases reported. Both had no complications related to covid. Excellent donors with KDPI <30. Cycle threshold 16 and above. Sequence 193 and 225. EPTS >85. Simulect and steroids used in both cases. Cold time short >16 hours. Both brain dead donors. LOS 7 and 8 days. PRA 0%. Donor blood group A and O. DGF in one recipient which recovered after 2 weeks see figure. The recipients had initially high antibody level which declined post transplant by 50%. See fig. Conclusion(s): Using Sars-CoV-2 donors is safe and provides a source of potential high quality organs in US Veterans who are generally underserved using informed consent. Full vaccination in recipient is a prerequisite. (Table Presented).

Transplant Graft TMA Injury Post COVID-19 Vaccination

Purpose: Vaccination against SARS-CoV-2 is essential. Complicating this effort are reports of a suboptimal response to the SARS-CoV-2 spike protein in patients on immunosuppressive medications and possible thrombotic microangiopathy (TMA) in renal transplant patients who receive the mRNA type vaccines. Method(s): 48 year old male with end stage renal disease who received a living unrelated transplant in 2015. Pre-operative creatinine was 10.42 mg/dL and decreased to 2.48 mg/dL within a week. Patient received Basiliximab induction and maintained on tacrolimus and mycophenolate (MMF). One month post-transplant patient was diagnosed with TMA. Tacrolimus was stopped and patient was switched to Sirolimus and continued on MMF. Patient was followed closely by transplant nephrology for the next 5 years with a baseline creatinine of 1.9 mg/dL, protein to creatinine ratio below 0.5 mg/mg and well controlled diabetes. No DSA Class I or II detected on regular testing. Patient was compliant with all prescribed medications. On January 25 2021 patient received Pfizer Vaccine. Second Pfizer vaccine administered on February 18 2021. A week later creatinine was noted to be 3.44 mg/dL. Repeat creatinine of 4.27 mg/dL. Biopsy revealed diffuse lymphocytic interstitial inflammation, peritubular capillaritis, and C4D negative. Findings consistent with chronic TMA. DSA testing revealed Class II DSA:DQ2 (SI-5933), Allosure 1.2 %. BK < 500 and CMV undetected. Patient received therapeutic plasma exchange, IV Ig infusion and steroids while on MMF and sirolimus. His creatinine decreased to 2.9 mg/dL on discharge. Over the next 6 months graft function deteriorated. He is now CKD stage 5 and under evaluation for a second transplant. Result(s): There are case reports of COVID-19 vaccine administration and transplant graft dysfunction. A possible mechanism involves the mRNA lipid nanoparticleencapsulated platform producing such a robust CD4 and CD8 T-cell response that pro-inflammatory cytokines are activated or that immune complex associated glomerular disease occurs resulting in the development of TMA in susceptible patients. Conclusion(s): A possible link between SARS CoV-2 vaccination and kidney transplant TMA warrants the implementation of close surveillance of vaccinated transplant patients, particularly susceptible individuals. More research is needed to determine if this link exists.

Bacterial Infections After Kidney Transplant Before and After the COVID-19 Pandemic

Purpose: Infectious complications are a major cause of mortality and morbidity after kidney transplantation. During the COVID-19 pandemia there were several changes in the management and behavior of patients after transplant. These included measures such as universal masking, social distancing and reinforcing hand hygiene. Our objective was to evaluate if these differences affected the incidence of infections after kidney transplant. Method(s): This is a retrospective cohort study of all kidney transplants performed in our institution from March 2017 to November 2020. We examined the incidence of wound infection, urinary tract infection (UTI), pneumonia, and gastrointestinal (GI) infections. Pediatric and multi-organ transplants were excluded. We used the Fisher test, Chi-squared test of independence and logistic regression models in the analysis. All tests were based on a level of significance of alpha=0.05. Result(s): A total of 185 deceased donor kidney transplant patients were reviewed, 153 before and 54 after the beginning of the COVID-19 pandemic in the United States. The incidence of wound infection, pneumonia and GI infection were similar before and after COVID (Table 1). There was a significant increase in UTI after the COVID pandemic, the main organisms isolated were Klebsiella pneumonia (50%) and E. coli (25%). Overall the presence of UTI and wound infection were significantly related (OR 4.2, p = 0.06). Other clinical variables such as age, BMI, KDPI, EPTS, and the occurrence of delayed graft function were not associated with UTI. COVID infection was present with similar incidence: 12% in patients transplanted before and 14.8% in patients transplanted after the onset of the pandemic. Induction with Thymoglobulin or Basiliximab was not significantly different before and after COVID, and the choice of induction was not associated with the rate of UTI. Conclusion(s): While multiple changes in the management of patients and patient behavior are different before and after the onset of the COVID-19 pandemic, this analysis did not find significant change in the incidence of infections except for UTI in comparative cohorts of kidney transplant recipients. This study did not identify specific factors associated with the increase of UTI in our population. However, in response certain measures were implemented, such as reducing the time to ureteral stent removal and giving 24 hrs of prophylactic antibiotics at the time of stent removal.

Incidence of Viral Infections in Kidney Transplant Recipients Using Reduced Induction and Steroid Free Maintenance Immunosuppression

Purpose: Viral infections (VI) commonly occur in the post-transplant period and higher cumulative doses of rATG have been correlated with higher rates of infection. However, basiliximab (BAS) has decreased risk of infection but increased risk of rejection due to a lower immunosuppressive profile. There is a shortage of literature evaluating choice and dosing of induction agent and the incidence of VI in kidney transplant recipients (KTR) receiving tacrolimus, mycophenolate and early steroid withdrawal. This study evaluated the incidence of VI in KTR receiving BAS, rATG low (< 3mg/kg), or high dose (> 3mg/kg) within 180 days post-transplant. Method(s): This single-center, retrospective study included adult KTR from July 2020-March 2021. KTR were excluded if they received a multi-organ transplant, no induction, or maintenance immunosuppression other than tacrolimus and mycophenolate. Induction was given based on patients' immunologic risk factors for rejection which included: age, race, cPRA, retransplantation, and DR HLA mismatch. The primary objective compared the incidence of VI with BAS, rATG low and high dose. Secondary outcomes included incidence of CMV, BKV, EBV, HSV, COVID-19, DGF, BPAR, de novo DSA, eGFR, tacrolimus levels, graft loss, and mortality within 180 days post-transplant. Result(s): There were 44 KTR who received BAS, 43 who received low rATG dose, and 129 who received high rATG dose. Statistically significant differences in baseline demographics included age, race, mean peak cPRA, and mean KDPI (due to institutional induction guidelines) [Table 1]. A larger proportion of high rATG patients experienced VI, followed by low rATG patients, p<0.01 [Table 2]. Increased incidence of CMV, BKV, and COVID-19 occurred in patients receiving rATG [Table 2]. Infections generally occurred earlier in the rATG groups [Table 2]. DSA was highest in the high dose rATG (14%) which was attributed to high risk factors for rejection, p=0.0146 [Table 3]. No differences in BPAR, DGF, graft failure, or mortality were seen between all groups within 180 days. Conclusion(s): KTR that received induction with any rATG dose had a higher incidence of viral infections compared to basiliximab. Induction with rATG may lead to an earlier onset of viral infections compared to basiliximab. Further review of data at one year post-transplant is planned to strengthen the results of this study.

Pre-Transplant Vaccine Induced SARS-CoV-2 Antibodies Decrease Following Induction Therapy for Kidney Transplantation

Purpose: Kidney transplant recipients (KT) and wait-listed individuals exhibit an impaired response to vaccinations. There is currently no data on the impact of induction immunosuppression followed by standard immunosuppression on the antibody (Ab) dynamics of wait-listed individuals undergoing KT. Here, we assess the SARS-CoV-2 antibody dynamics prior and one month following transplantation Methods: Previously immunized wait-listed patients (2 mRNA vaccine doses: mRNA-1273 or BNT162b2 at least 14 days prior to KT) who subsequently underwent KT were included. Serum was collected within 24 hours prior to transplantation and 3-4 weeks following transplantation. ELISAs measuring anti-S and anti-RBD titers on pre- and post-transplant samples were performed. Serial dilutions of patient samples were prepared and AUC were calculated for paired samples from each participant. Paired samples were run simultaneously to reduce the effect of interplate variability. Wilcoxon and Mann-Whitney test were used to compare paired and unpaired samples, respectively Results: 35 patients were included (12 LKT/23 DDKT). 34 patients received induction with ATG, 1 with Basiliximab. Standard immunosuppression consisted of prednisone (2-week taper), mycophenolate and tacrolimus. 61% received mRNA- 1273 and 39% BNT162b2. We found no difference in Abs between vaccines. Anti- RBD Ab and anti-S Ab had a significant decline following KT at the one-month endpoint (anti-RBD Pre-KT: 1581 vs Post-KT: 473 p<0.0001 anti-S Ab Pre-KT: 4058 vs 1739 p<0.0001). 29 wait-listed patients were on dialysis and had lower pre-transplant Abs (anti-RBD dialysis: 1508 vs no dialysis: 3790 p=0.5. Anti-S Ab dialysis: 3841 vs no dialysis: 10058 p=0.17). The differences remained post-KT. 3 patients developed COVID-19 following transplantation (median: 123 days). They had lower pre- and post-transplant Ab (post-transplant anti-RBD COVID-19: 181 vs no COVID-19: 486 p=0.3, anti-S COVID-19: 1672 vs no COVID-19: 613 vs no COVID-19: 1801 p=0.4) Conclusion(s): Induction immunosuppression followed by standard immunosuppression led to a significant decrease of both anti-S and anti-RBD ab in KT recipients. Waitlisted individuals on dialysis had lower Abs both pre-and post-transplant. Patients who developed post KT COVID-19 had lower Ab levels. Our data suggests that immediate post-transplant KTs may require additional vaccinations against COVID-19.

ARE ABO INCOMPATIBLE KIDNEY TRANSPLANT RECIPIENTS AT HIGHER RISK OF INFECTIONS?-A SINGLE CENTER EXPERIENCE

Introduction: Because of the limited donor pool, transplants are being done across the blood group and even HLA incompatibility barriers. But this comes at the cost of increased immunosuppression and the side effects. Effect of this intensified immunosuppression on the incidence of post transplant infections and the type of infection has not been studied extensively. Methods: We retrospectively analysed the incidence of infection in ABO incompatible transplants (ABOi) and compared it with propensity matched cohort of ABO compatible transplants(ABOc) over the same timeframe i.e. 2011 to April 2019. using hospital eHIS record system. Patients were matched with 1:2 ratio (ABOi: ABOc) for age (<60yr, >60yrs),sex, number of previous transplants, pretransplant infections, history of prior immunosuppression, diabetic status, NODAT, and induction agent used. Desensitization protocol for ABO incompatible transplant includes rituximab with double filtration plasmapheresis, plasmapharesis or immunoadsorption to target anti blood group titre of 8. Patient with high immunological risk (e.g.second transplant, HLA incompatible) receive ATG induction while others receive basiliximab induction. Valganciclovir prophylaxis was given only in patients with ATG induction. Results: [Formula presented] [Formula presented] During the study period 89 patients underwent ABOi transplants which were compared with 178 ABOc transplants. (Table1)Mean follow up duration was 50.45months (SD 26.8) in ABOi group and 49.47months (SD28.7) in ABOc group. 17% patients lost to follow up with their last follow up being more than 2 years before. Incidence of overall infections was similar in both the groups (59% (43/89) Vs 44.3% (79/178);p=0.6). (Table2) Incidence of urinary tract infections(UTI)was significantly more in ABOi group vs ABOc group.(23.5% (21/89) vs 11.79% (21/178);p=0.019). Cytomegalovirus infections (CMV) were significantly more in ABOi group 12.3% (11/89) as compared to ABOc group 5% (9/187) (p=0.04). All the patients with CMV infection were CMV IgG positive pretransplant except 2, one from ABOc group who was CMV IgG negative and another from ABOi group who’s pretransplant CMV serology was unavailable. There was no significant difference in incidence of fungal infection, pneumocystis infection, diarrheal infections (other than CMV),pneumonia (other than CMV, PCP, fungal), Herpes, BKV infection. Incidence of post-transplant tuberculosis (3.3% (3/89) Vs 2.8% (5/178);p=1.0) and SARS COV2 infections (12.3% (11/89) vs 9% (16/178);p=0.39 was similar in both the groups. Patient survival was similar in both the groups i.e.95.5% but death censored graft loss was significantly more in ABOi group 0.9% (8/89) as compared ABOc group 0.3% (5/178) p=0.03. Reason of graft loss in all the patients was immunological and not infection. Infection was cause for death in three ABOi patients and four ABOc patients. Conclusions: Overall incidence of infections in ABOi transplants was similar to Abo compatible transplant. Incidence of UTIs and CMV infections were significantly higher in ABOi group. No conflict of interest

Transplant Graft TMA Injury Post COVID-19 Vaccination

Vaccination against SARS-CoV-2 is essential. Complicating this effort are reports of a suboptimal response to the SARS-CoV-2 spike protein in patients on immunosuppressive medications and possible thrombotic microangiopathy (TMA) in renal transplant patients. 48-year-old male who received a living unrelated transplant in 2015. Pre-operative creatinine was 10.42 mg/dL and decreased to 2.48 mg/dL within a week. Patient received Basiliximab induction and maintained on tacrolimus and mycophenolate (MMF). One month post-transplant patient was diagnosed with TMA. Tacrolimus was stopped and patient was switched to Sirolimus and continued on MMF. Patient was followed closely by transplant nephrology for the next 5 years with a baseline creatinine of 1.9 mg/dL, protein to creatinine ratio below 0.5 mg/mg and well controlled diabetes. No DSA Class I or II detected on regular testing. Patient was compliant with all prescribed medications. On January 25 2021 patient received Pfizer Vaccine. Second Pfizer vaccine administered on February 18 2021. A week later creatinine was noted to be 3.44 mg/dL. Repeat creatinine of 4.27 mg/dL. Biopsy revealed diffuse lymphocytic interstitial inflammation, peritubular capillaritis, and C4D negative. Findings consistent with chronic TMA. DSA testing revealed Class II DSA:DQ2 (SI- 5933), Allosure 1.2 %. BK < 500 and CMV undetected. Patient received therapeutic plasma exchange, IV Ig infusion and steroids while on MMF and sirolimus. His creatinine decreased to 2.9 mg/dL on discharge. Over the next 6 months graft function deteriorated. He is now CKD stage 5 and under evaluation for a second transplant. There are case reports of COVID-19 vaccine administration and transplant graft dysfunction. A possible mechanism involves the mRNA lipid nanoparticle-encapsulated platform producing such a robust CD4 and CD8 T-cell response that pro-inflammatory cytokines are activated or that immune complex associated glomerular disease occurs resulting in the development of TMA in susceptible patients. A possible link between SARS CoV-2 vaccination and kidney transplant TMA warrants the implementation of close surveillance of vaccinated transplant patients, particularly susceptible individuals. More research is needed to determine if this link exists.

INDUCTION IMMUNOSUPPRESSION AND OUTCOME IN EARLY KIDNEY TRANSPLANT RECIPIENTS WITH COVID-19

BACKGROUND AND AIMS: COVID-19 in kidney transplants has a high risk of complications and mortality, especially in older recipients diagnosed during the early period after transplantation. Management of immunosuppression has been challenging during the pandemic. We investigated the impact of induction immunosuppression, either basiliximab or thymoglobulin, on the clinical evolution of kidney transplants developing COVID-19 during the early period after transplantation. METHOD: Kidney transplant recipients with <6 months with a functioning graft diagnosed of COVID-19 from the initial pandemic outbreak (March 2020) until 31 July 2021 from different Spanish centres participating in a nationwide registry. RESULTS: A total of 127 patients from 17 Spanish centres developed COVID-19 during the first 6 months after transplantation, 73 (57.5%) received basiliximab and 54 (42.5%) thymoglobulin. Demographics were not different between groups, but patients receiving thymoglobulin were more sensitized (cPRA of 32.7% ± 40.8% versus 5.6% ± 18.5%) and more frequently re-transplanted (30% versus 4%). Recipients older than 65 years treated with thymoglobulin showed the highest rate of acute respiratory distress syndrome [64.7% versus 37.1% for older recipients receiving thymoglobulin and basiliximab (P < .05), and 23.7% and 18.9% for young recipients receiving basiliximab and thymoglobulin (P > .05)] and the poorest survival [mortality rate of 64.7% and 42.9% for older recipients treated with thymoglobulin and basiliximab, respectively (P < .05), and 8.1% and 10.5% for young recipients treated with thymoglobulin and basiliximab (P > .05)]. Older recipients treated with thymoglobulin showed the poorest survival in the Cox's regression model adjusted for comorbidities. CONCLUSION: Thymoglobulin should be used with caution in older recipients during the present pandemic era.

IMPACT OF DE NOVO IMMUNOSUPPRESSION IN THE COVID-19 SEROLOGICAL STATUS AT KIDNEY TRANSPLANTATION

BACKGROUND AND AIMS: COVID-19 infection has heavily impacted our national health system since March-2020. Although the kidney transplant (KT) activity was strongly reduced initially, nowadays it is partially recovered by using 'COVID-clean' pathways and vaccination of KT candidates since February-2021. However, scarce information is available regarding how de novo KT immunosuppression influences the serological status of vaccinated recipients. METHOD: We reviewed the course of 38 de novo KT recipients transplanted between March-September 2021 fully vaccinated before KT. SARS-CoV-2 IgG antibodies against Spike (IgG-S) before and after KT (median: 32 days) were quantified with a serological assay (positive ≥13.0 AU/mL). RESULTS: Of 38 recipients, 35 showed positive IgG-S at KT (92%). We exclude from the analysis, 4 recipients with COVID infection which interfered the analysis and 5 with inappropriate samples. The remaining 26 recipients had received the second dose of the mRNA vaccine a median time of 48 days before the pre-KT IgG determination. All patients maintained IgG-S over the cut-off after KT, but we observed that half de novo recipients (53.8%) showed a 50% reduction in the level of IgG-S at 1 month: 12/20 (60%) of those who received induction with basiliximab and 2/6 (33%) who received thymoglobulin. Regarding the impact of maintenance immunosuppression under induction with basiliximab, the IgG-S levels halved in 50% of those with tacrolimus-mycophenolate and 67% with tacrolimus-everolimus. The restricted analysis of IgG-S levels excluding five outliers before KT (>800 AU/mL) showed the most intense reduction in three KT recipients who received thymoglobulin-tacrolimus- mycophenolate (263.8 versus 68.8, 74%) compared with seven basiliximab-tacrolimus-mycophenolate cases (494.4 versus 359.8, 27%) and eleven basiliximab-tacrolimus-everolimus (344.0 versus 306.4, 11%) KT recipients. CONCLUSION: Immunosuppression in de novo KT recipients reduces significantly the seroprotective levels of antibodies anti-Spike induced by COVID m-RNA vaccines in more than half the recipients. In our experience, the combination of thymoglobulin, tacrolimus and mycophenolate produces a more intense reduction than the combination of basiliximab with tacrolimus and mycophenolate or everolimus.

Oral and Poster Presentations

To test this, we used the hierarchical PBM clustering of 122 HLA class I allotypes (44 HLA-A, 63 HLA-B, and 18 HLA-C) to identify 21 distinct PBM groups. O14 The pre-transplant non-HLA antibody burden predicts the development of histology of antibody-... Aleksandar Senev 1, Bryan Ray 2, Jayasree Hariharan 2, Christine Heylen 2, Marie-Paule Em... 1 KU Leuven, Belgium, 2 Immucor Inc, United States B Correspondence: b aleksenev@yahoo.com In this study we aimed to investigate the role of 82 different non-HLA antibodies in the occurrence of histology of ABMR after kidney transplantation. We developed an assay that estimated the binding strength of HLA II-peptide interaction by measuring the cell-surface expression of HLA II-peptide fusion construct. In the present study, we used a newly developed HLA II-peptide interaction assay to identify HLA II-binding regions in SARS-CoV-2 Spike and the mutations that might affect the interaction with HLA II. [Extracted from the article] Copyright of HLA: Immune Response Genetics is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)