Comparison of Thymoglobulin and Grafalon as Induction Agents in Renal Transplantation: A Prospective Study.

BACKGROUND: Induction immunosuppression is used to reduce the incidence of acute rejection and prevent delayed graft function. The 2 rabbit anti-thymocyte globulins- thymoglobulin and Grafalon (ATG Fresenius) have been commonly used for induction immunosuppression and treatment of acute rejection in solid organ transplantation. There are very few studies comparing the efficacy and side effects of both the anti-thymocyte globulins therefore this prospective study comparing the 2 types of anti-thymocyte globulins would be of clinical interest. PATIENTS AND METHODS: This prospective single center study was conducted at Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, India from April 2019 to June 2020. Sixty-two ABO-compatible renal transplant recipients were included in the study. They were divided in 2 groups of 31 patients each. One group received thymoglobulin (3 mg/kg) and the second group received Grafalon (6 mg/kg). All patients were followed up for 12 months and the 2 groups were compared for incidence of rejections, infections, graft function, patient survival, and graft survival. RESULTS: There was no significant difference in the incidence of rejections, infective episodes, graft function, posttransplant diabetes mellitus, graft survival and patient survival in thymoglobulin or Grafalon groups. The hematological parameters were similar in both groups at 7 days, 1 month, and 6 months of follow-up. The absolute lymphocyte count was significantly lower in the thymoglobulin group at 12 months posttransplant. CONCLUSIONS: Thymoglobulin and Grafalon were found to be equivalent in terms of safety and efficacy in short term, with no difference in rejections, infections, graft survival, or patient survival.

Incidence of COVID-19 and Identification of Possible Risk Factors Associated with COVID-19 in Acute Renal Transplant Recipients in Pakistan.

BACKGROUND Renal transplant recipients are susceptible to increased mortality with COVID-19 infection. There is insufficient data regarding risk factors for COVID-19 disease acquisition. We aimed to identify them here. MATERIAL AND METHODS We enrolled Pakistani renal transplant recipients from February 10, 2020, to March 18, 2021, and actively tracked their baseline health status, transplant characteristics, comorbidities, immunosuppressive therapies, and post-transplant follow-ups until September 2021. Furthermore, we formulated 2 questionnaires for their compliance assessment with COVID-19-preventive measures. We also identified COVID-19 disease acquisition, symptomatology, and management. RESULTS Among the 50 enrolled patients, 14 (28%) patients developed COVID-19, which is higher than the incidence observed in general Pakistani population (0.55%). Their mean age was 35.38 years ±11.69 SD years, and 82% of patients were males. The following factors were independently associated with COVID-19 disease: female gender (P value: 0.042), diabetes mellitus (P value: 0.002), anti-thymocyte globulin (ATG) induction (P value: 0.006), in-person follow-ups (P value: 0.000), prolonged immediate and late post-transplant hospital stays (P value: 0.019 and 0.000, respectively), raised post-transplant serum creatinine (P value: 0.019), and COVID-19 protective measures non-compliance (P value: 0.000). Out of 14 infected recipients, 92.85% required symptomatic management and overall mortality was 0%. CONCLUSIONS Female gender, diabetes mellitus, ATG induction, in-person follow-ups, prolonged hospital stays, raised post-transplant serum creatinine, and COVID-19-protective measures non-compliance were associated with the higher acquisition of SARS-CoV-2 infection. By taking concrete measures against these risk factors, we can continue renal transplants, as overall mortality was lower than in the general Pakistani population (2%).

A pilot randomized controlled trial of de novo belatacept-based immunosuppression following anti-thymocyte globulin induction in lung transplantation.

The development of donor-specific antibodies (DSA) after lung transplantation is common and results in adverse outcomes. In kidney transplantation, Belatacept has been associated with a lower incidence of DSA, but experience with Belatacept in lung transplantation is limited. We conducted a two-center pilot randomized controlled trial of de novo immunosuppression with Belatacept after lung transplantation to assess the feasibility of conducting a pivotal trial. Twenty-seven participants were randomized to Control (Tacrolimus, Mycophenolate Mofetil, and prednisone, n = 14) or Belatacept-based immunosuppression (Tacrolimus, Belatacept, and prednisone until day 89 followed by Belatacept, Mycophenolate Mofetil, and prednisone, n = 13). All participants were treated with rabbit anti-thymocyte globulin for induction immunosuppression. We permanently stopped randomization and treatment with Belatacept after three participants in the Belatacept arm died compared to none in the Control arm. Subsequently, two additional participants in the Belatacept arm died for a total of five deaths compared to none in the Control arm (log rank p = .016). We did not detect a significant difference in DSA development, acute cellular rejection, or infection between the two groups. We conclude that the investigational regimen used in this study is associated with increased mortality after lung transplantation.

Safety of Antithymocyte Globulin Use in Kidney Graft Recipients During the COVID-19 Pandemic.

BACKGROUND There are many safety concerns regarding the use of antithymocyte globulin (ATG) in kidney transplant recipients (KTRs) during the ongoing COVID-19 pandemic. Hereby, we present our recent experience with ATG administration both as induction therapy and as an anti-rejection treatment. MATERIAL AND METHODS We retrospectively analyzed all patients transplanted during the first 12 months of the COVID-19 pandemic who were treated with thymoglobulin. The ATG dosing, lymphocyte number and percentage in blood smear, adverse effects (thrombocytopenia and infectious complications), and kidney graft function up to 12 months and patients' outcomes were analyzed and compared to KTRs who received basiliximab induction. RESULTS During pandemic, a total of 31 patients were treated with ATG and 59 received basiliximab. The median cumulative ATG doses were 275 (175-325) mg in the induction subgroup and 263 (200-275) mg in the anti-rejection treatment subgroup. Mild thrombocytopenia was noted in 7 (22.6%) and 13 (29.5%) patients, respectively. There were more infectious complications among patients treated with ATG as compared with the basiliximab subgroup (32.3 vs 10.2%, P<0.01), but there were similar incidence rates of thrombocytopenia. Kidney graft function up to 12 months after transplant was comparable (1.1 [1.0-1.9] vs 1.1 [1.0-1.4] mg/dl, respectively). CONCLUSIONS 1. ATG use in the induction protocol or as the anti-rejection treatment during the COVID-19 pandemic appears to be safe and the risk of adverse events is acceptable. 2. During the COVID-19 pandemic the necessary use of ATG should not be postponed, especially in KTRs with increased immunologic risk.

Activity and short-term outcomes of kidney transplantation during the COVID-19 pandemic. / Actividad y resultados a corto plazo del trasplante renal durante la pandemia COVID-19.

INTRODUCTION: During the COVID-19 pandemic, the national transplant activity has been reduced due to the overload of the health system and concern for patient safety in this situation. The aim of our work is to expose the activity of kidney transplantation in Cantabria during the state of alarm, as well as to assess the safety of the transplantation program. MATERIAL AND METHODS: Retrospective study of kidney transplants performed in our Center from the beginning of the state of alarm until the beginning of the lockdown easing in Cantabria. Descriptive analysis of the demographic data of recipients and their donors, intraoperative data and postoperative outcomes. Comparative analysis with the data of the same period in 2017-2019, by means of the χ2 for categorical variables, Student's T and Mann-Whitney U tests in case of quantitative variables of normal and non-normal distribution, respectively. RESULTS: Fifteen kidney transplants were performed in the period described. Delayed renal function (DRF) was seen in 7.5% of patients, and 26.6% showed data of acute rejection; no patient presented COVID-19 disease. Comparative analysis showed a remarkable increase in the number of transplants in comparison with previous periods (15 vs 5.6), at the expense of donors from outside Cantabria (93.3%). We found no statistically significant differences in terms of cold ischemia time (p=0.77), DRF (p=0.73), need for dialysis (p=0.54), or appearance of post-surgical complications (p=0.61). CONCLUSIONS: The evolution of the pandemic in our region, and the adoption of strict protective measures has allowed the early and safe resumption of the renal transplantation program, increasing the number of transplants performed compared to previous years and maintaining comparable early post-operative results.

Successful liver transplantation in a patient recovered from COVID-19.

Transplantation in potential candidates who have recently recovered from COVID-19 is a challenge with uncertainties regarding the diagnosis, multi-organ systemic involvement, prolonged viral shedding in immunocompromised patients, and optimal immunosuppression. A 42 year male with alcoholic hepatitis underwent a successful deceased donor liver transplantation 71 days after the initial diagnosis of COVID-19. At the time of transplant, he was SARS-CoV-2 PCR negative for 24 days and had a MELD score of 33. His post-operative course was complicated by acute rejection which responded to intense immune-suppression using T-cell depletion and steroids. He was discharged with normal end-organ function and no evidence of any active infection including COVID-19. Prospective organ transplant recipients who have recovered from COVID-19 can be considered for transplantation after careful pre-transplant evaluation, donor selection, and individualized risk-benefit analysis.

COVID-19 in a lung transplant recipient: Exploring the diagnostic role of circulating exosomes and the clinical impact of advanced immunosuppression.

Exosomes isolated from plasma of lung transplant recipients with allograft injury contain donor-derived lung self-antigens (collagen V and Kα1 tubulin) and human leukocyte antigen (HLA) molecules. We present a case of a 76-year-old, female lung transplant recipient treated for acute cellular rejection with methylprednisolone and anti-thymocyte globulin, who subsequently contracted SARS-CoV-2 and developed a sharp increase in the mean fluorescent intensity of anti-HLA antibodies. Analysis of circulating exosomes during rejection, but before SARS-CoV-2 infection, revealed the presence of lung self-antigens and HLA class II molecules. After the patient contracted SARS-CoV-2, exosomes with the SARS-CoV-2 spike protein were also found. After resolution of infectious symptoms, exosomes with SARS-CoV-2 spike protein were no longer detected; however, exosomes with lung self-antigens and HLA class II molecules persisted, which coincided with a progressive decline in spirometric flows, suggesting chronic lung allograft dysfunction. We propose that the analysis of circulating exosomes may be used to detect allograft injury mediated by both rejection and infection. Furthermore, the detection of exosomes containing viral proteins may be helpful in identifying allograft injury driven by viral pathogens.