SARS-CoV-2 Antibodies Transitions After Vaccination in Solid Organ Transplant Recipients: Multicenter Study in Japan

Purpose: For purpose of SARS-CoV-2 infection control, vaccination was started in worldwide, however, low reactivity of antibody production after vaccination is a concern for solid organ transplant (SOT) recipients. In general, antibody titers would be peaked within one month after vaccination for the healthy population, there are few report about SOT recipients vaccination. We explored antibody transitions in SOT recipients after vaccination. Method(s): A total of 641 solid organ transplant recipients were enrolled (481 kidney, 51 liver, 54 heart, 20 lung, and 35 simultaneous pancreas-kidney). All participants were administered the two-dose regimen mRNA vaccine (BNT162b2, Pfizer or mRNA-1273, Moderna), as indicated. SARS-CoV-2 antibodies were measured total 5 times throughout vaccination (Elecsys, Roche). Result(s): The antibody titer and positive rate were both elevated until three months and declined at six months after vaccination (positive rate;10.4%, 41.2%, 68.6%, 56.9%, in each) (Fig.1). Lung and kidney-pancreas transplant recipients showed poor antibody titer elevation compared with other organ transplantation (Fig. 2). Antibody titers be significant low by more than 60 years old compared with other ages (Fig.3). Conclusion(s): The antibody titer and positive rate transition of SOT recipients were quite different compared with the health population. The acquisition of antibody was different depends on type of SOT. (Figure Presented).

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

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

Hepatitis C (HCV) Positive Recipients and/or Donors in Pancreas Transplantation - A Registry Analysis

Purpose: Pancreas transplantation (PT) is the best long-term option for patients with labile diabetes and end-stage-renal disease. The mortality on the waitlist is high;patients should receive a transplant as early as possible. There remains a shortage of high-quality organ donors suitable for pancreas (and kidney) transplantation. PT in HCV positive recipients using a negative donor (R+/D-) has been performed but not vice versa (no R-/D+ transplants). After the advent of new, oral, and directacting antiviral agents, the option to use HCV+ deceased donor organs has become possible;anti-HCV treatment is started right after transplant. Method(s): All reported cases of R+/D- and R-/D+ transplants performed since 1/1/2019 were included in this study. Descriptive analysis of patient, donor characteristics, and outcome was performed. Patient and graft survival was assessed using the Kaplan-Meier method. Result(s): 38 R+D-, 36 R-D+, and 2 R+D+ transplants were identified. The majority were simultaneous pancreas kidney (SPK) transplants. Only one R-D+ pancreas after kidney transplant (PAK), and 8 pancreas transplants alone (PTA all R+D-) were performed. Tables 1 and 2 show donor and recipient characteristics for SPK transplants. The donors were excellent young donors, mostly males dying of trauma, but, in the R-D+ category, in the majority previous drug users. Notably, the waitingtime for R-D+ recipients was under 3 months in 50% of transplants. Outcome of the HCV NAT test at 6 months is shown in Table 3. The 2 positive patients at 6 months were negative at 1 year follow-up. Patient and graft survival is shown in Table 3. The 3 early deaths in the R-D+ group were 1 trauma, 1 bacterial infection due to technical problems, and 1 possible COVID-19 infection. All 3 patients died with functioning pancreas and kidney grafts. Conclusion(s): Pancreas transplantation is considered by many a non-life-saving procedure and, therefore, patients and donors are carefully chosen. What is neglected is the fact that the mortality of diabetic patients while waiting is high. Hence, it is essential to transplant as early as possible. In contrast to solitary pancreas transplants, the SPK waiting time is long. The advent of new HCV treatment modalities makes safe and successful transplants possible for HCV+ recipients and from HCV+ donors possible. HCV+ donors are usually young and excellent donors who fulfill acceptance criteria for pancreas transplantation. Follow-up time for patients in this study is short, but our preliminary results show that the use of an HCV+ donor results in safe and successful pancreas transplant outcome.

COVID-19 vaccination impact on presensitization status of patients awaiting pancreas and kidney/pancreas transplantation

Blood transfusions, pregnancies and previous organ transplantation can cause immunization. Infection and vaccination could alter the recipient sensitization status. Here we evaluated COVID-19 vaccination effect on presensitization status of Pancreas/Renal-Pancreas waitlisted patients in Pisa Hospital (Italy). We enrolled 27 patients (15 female and 12 male) which received a complete vaccination cycle (CVC) of COVID-19 mRNA vaccines (BNT162b2-Pfizer/BioNTech or mRNA-1273-Moderna);15/27 patients received third dose (booster). X-MAP technology (Luminex-beads) was used to identify class I and II anti-HLA antibody specificity. The population was studied before vaccination (BV) and 2 weeks after CVC and booster. Sensitivity status change (qualitative analysis) and mean fluorescence intensity (MFI) changes (semi-quantitative analysis) were calculated by Excel using specific functions created “ad hoc”: AntigenDifference() and AntigenValueSum(). We observed new specificities after CVC in 11/27 patients: class I (29%), class II (33%) and class I + II (22%);after the booster class I, class II and class I + II increased by 35%, 50% and 28%, respectively. No statistically significant differences were observed in the MFI mean value between CVC, booster and BV group (p > 0.05, Mann-Whitney U test). COVID-19 vaccination could induce changes in the percentage of circulating antibodies directed against HLA and should be considered in the pre-transplant risk assessment.

Determining Associations Between Dietary Vitamin D Intake and Episodes of Infection, Rejection and Length of Stay in Hospital in Kidney and Kidney-Pancreas Transplant Patients

Background: Vitamin D is a pleiotropic hormone and plays a major role in protecting the body against infection and regulating inflammation. Research suggests that kidney [K] recipients with low levels of 25 hydroxyvitamin D3 (25(OH)D3) have a higher incidence of infections and rejection. Furthermore, research indicates low dietary vitamin D intake is positively associated with a lowered 25(OH)D3 serum levels. However, no research exists examining vitamin D intake and length of stay in the hospital [LOS(H)] in the K and K-pancreas [KP] population. Objective: The objective was to determine the associations between dietary vitamin D intake and episodes of infection, rejection, and LOS(H) in K+KP transplant recipients. Methods: Methods: A prospective investigation of 110 K+KP transplant patients with follow-up at 3, 6, 9, and 12-months posttransplant was undertaken. Due to barriers encountered by the COVID-19 pandemic, data was collected at baseline and 3 months only. Dietary vitamin D intake was obtained through modified Automated Multi-pass Method 24-hour (24HR) dietary recall at baseline which were analyzed by ESHA Food Processor. Vitamin D intake amounts did not include intake from supplementation. Episodes of infection, rejection and LOS(H) were recorded at 3 months post-transplant. Demographic data was determined using frequencies and means ± SD. Associations were determined using Spearman's correlations. Statistical analysis was preformed using SPSS v27 and statistical significance was determined using p < 0.05. Results: Results/Discussion: 100K and 10KP were available for evaluation. Participants were 64% male and 36% female, mean age: 50.5 ± 13.9 years, and BMI: 28.6 ± 5.5kg/m2. 99% of our patient population did not meet their recommended dietary allowance [RDA] for vitamin D intake by food alone, thus, it is possible that a portion of our patient population would have deficient serum 25(OH)D3 levels. No significant associations were found between vitamin D intake and episodes of infection, rejection, or LOS(H) at 3 months. We report 25% vitamin D intake from dairy products and only 2% from margarine. Lower intake of dairy products may be related to the recommendation of a potassiumrestricted nutrition care plan in the K+KP population. Conclusion: Conclusion: We report no association between vitamin D intake and episodes of infection, rejection, or LOS(H) likely due to the fact that the majority of our population's dietary intake did not meet vitamin D intake recommendations. Our future research will focus on improving patient vitamin D intake, supplementation and investigating 25(OH)D3 levels in association with episodes of infection, rejection, and LOS(H).