Patterns in Use and Transplant Outcomes Among Adult Recipients of Kidneys From Deceased Donors With COVID-19.

Importance: While the COVID-19 pandemic enters a new phase and the proportion of individuals with a previous COVID-19 diagnosis increases, the national patterns in kidney use and medium-term kidney transplant (KT) outcomes among patients receiving kidneys from active or resolved COVID-19-positive donors remain unknown. Objective: To evaluate the patterns in kidney use and KT outcomes among adult recipients of kidneys from deceased donors with active or resolved COVID-19. Design, Setting, and Participants: This retrospective cohort study was conducted using national US transplant registry data from 35 851 deceased donors (71 334 kidneys) and 45 912 adult patients who received KTs from March 1, 2020, to March 30, 2023. Exposure: The exposure was donor SARS-CoV-2 nucleic acid amplification test (NAT) results, with positive NAT results within 7 days before procurement defined as active COVID-19 and positive NAT results 1 week (>7 days) before procurement defined as resolved COVID-19. Main Outcomes and Measures: Primary outcomes were kidney nonuse, all-cause kidney graft failure, and all-cause patient death. Secondary outcomes were acute rejection (ie, rejection in the first 6 months after KT), transplant hospitalization length of stay (LOS), and delayed graft function (DGF). Multivariable logistic regression analyses were performed for kidney nonuse, rejection, and DGF; multivariable linear regression analyses were performed for LOS; and multivariable Cox regression analyses were performed for graft failure and all-cause death. All models were adjusted for inverse probability treatment weighting. Results: Among 35 851 deceased donors, the mean (SD) age was 42.5 (15.3) years; 22 319 (62.3%) were men and 23 992 (66.9%) were White. Among 45 912 recipients, the mean (SD) age was 54.3 (13.2) years; 27 952 (60.9%) were men and 15 349 (33.4%) were Black. The likelihood of nonuse of kidneys from active or resolved COVID-19-positive donors decreased over time. Overall, kidneys from active COVID-19-positive donors (adjusted odds ratio [AOR], 1.55; 95% CI, 1.38-1.76) and kidneys from resolved COVID-19-positive donors (AOR, 1.31; 95% CI, 1.16-1.48) had a higher likelihood of nonuse compared with kidneys from COVID-19-negative donors. From 2020 to 2022, kidneys from active COVID-19-positive donors (2020: AOR, 11.26 [95% CI, 2.29-55.38]; 2021: AOR, 2.09 [95% CI, 1.58-2.79]; 2022: AOR, 1.47 [95% CI, 1.28-1.70]) had a higher likelihood of nonuse compared with kidneys from donors without COVID-19. Kidneys from resolved COVID-19-positive donors had a higher likelihood of nonuse in 2020 (AOR, 3.87; 95% CI, 1.26-11.90) and 2021 (AOR, 1.94; 95% CI, 1.54-2.45) but not in 2022 (AOR, 1.09; 95% CI, 0.94-1.28). In 2023, kidneys from both active COVID-19-positive donors (AOR, 1.07; 95% CI, 0.75-1.63) and resolved COVID-19-positive donors (AOR, 1.18; 95% CI, 0.80-1.73) were not associated with higher odds of nonuse. No higher risk of graft failure or death was found in patients receiving kidneys from active COVID-19-positive donors (graft failure: adjusted hazard ratio [AHR], 1.03 [95% CI, 0.78-1.37]; patient death: AHR, 1.17 [95% CI, 0.84-1.66]) or resolved COVID-19-positive donors (graft failure: AHR, 1.10 [95% CI, 0.88-1.39]; patient death: AHR, 0.95 [95% CI, 0.70-1.28]). Donor COVID-19 positivity was not associated with longer LOS, higher risk of acute rejection, or higher risk of DGF. Conclusions and Relevance: In this cohort study, the likelihood of nonuse of kidneys from COVID-19-positive donors decreased over time, and donor COVID-19 positivity was not associated with worse KT outcomes within 2 years after transplant. These findings suggest that the use of kidneys from donors with active or resolved COVID-19 is safe in the medium term; further research is needed to assess longer-term transplant outcomes.

OPTN/SRTR 2021 Annual Data Report: Lung.

The number of lung transplants has continued to decline since 2020, a period that coincides with the onset of the COVID-19 pandemic. Lung allocation policy continues to undergo considerable change in preparation for adoption of the Composite Allocation Score system in 2023, beginning with multiple adaptations to the calculation of the Lung Allocation Score that occurred in 2021. The number of candidates added to the waiting list increased after a decline in 2020, while waitlist mortality has increased slightly with a decreased number of transplants. Time to transplant continues to improve, with 38.0% of candidates waiting fewer than 90 days for a transplant. Posttransplant survival remains stable, with 85.3% of transplant recipients surviving to 1 year; 67%, to 3 years; and 54.3%, to 5 years.

OPTN/SRTR 2021 Annual Data Report: Introduction.

The OPTN/SRTR 2021 Annual Data Report presents the status of the solid organ transplantation system in the United States from 2010 through 2021. Organ-specific chapters are presented for kidney, pancreas, liver, intestine, heart, and lung transplant. Each organ-specific chapter is organized to present waitlist information, donor information (both deceased and living, as appropriate), transplant information, and patient outcomes. Data pertaining to pediatric patients are generally presented separately from the adult data. In addition to the organ-specific chapters, you will find chapters dedicated to deceased organ donation, vascularized composite allograft, and the COVID-19 pandemic. The data presented in the Annual Data Report are descriptive in nature. In other words, most tables and figures present raw data without statistical adjustment for possible confounding or changes over time. Therefore, the reader should keep in mind the observational nature of the data when attempting to draw inferences before trying to ascribe a cause to any observed patterns or trends. This introduction provides a brief overview of trends in waitlist and transplant activity. More detailed descriptions can be found in the respective organ-specific chapters.

OPTN/SRTR 2021 Annual Data Report: COVID-19.

This chapter updates the COVID-19 chapter from the 2020 Annual Data Report with trends through February 12, 2022, and introduces trends in COVID-19-specific cause of death on the waiting list and posttransplant. Transplant rates remain at or above prepandemic levels for all organs, indicating a sustained transplantation system recovery following the initial 3-month disruption due to the onset of the pandemic. Posttransplant mortality and graft failure remain a concern in all organs, with rates surging corresponding to waves of the pandemic. Waitlist mortality due to COVID-19 is also a concern, particularly among kidney candidates. While the recovery of the transplantation system has been sustained in the second year of the pandemic, ongoing efforts should focus on reducing posttransplant and waitlist mortality due to COVID-19, and graft failure.

OPTN/SRTR 2021 Annual Data Report: Kidney.

The year 2021 marked both successes and challenges for the field of kidney transplantation, in the context of the ongoing COVID-19 pandemic and broader geographic organ distribution. The total number of kidney transplants in the United States reached a record count of 25,487, driven by growth in deceased donor kidney transplants. The total number of candidates listed for deceased donor kidney transplant rose slightly in 2021 but remained below 2019 listing levels, with nearly 10% of candidates having been waiting 5 years or longer. Pretransplant mortality declined slightly among candidates of Black, Hispanic, and other races, in parallel with increasing numbers of Black and Hispanic transplant recipients. In the context of broader organ sharing, there is growing disparity in pretransplant mortality among non-metropolitan compared with metropolitan residents. The proportion of deceased donor kidneys recovered but not used for transplant (nonuse rate) rose to a high of 24.6% overall, with greater nonuse among biopsied kidneys (35.9%), kidneys from donors aged 55 years or older (51.1%), and kidneys with kidney donor profile index (KDPI) of 85% or greater (66.6%). Nonuse of kidneys from donors who are hepatitis C virus (HCV) antibody positive only slightly exceeded that of HCV antibody-negative donors. Disparities in access to living donor kidney transplant persists, especially for non-White and publicly insured patients. Delayed graft function continues an upward trend and occurred in 24% of adult kidney transplants in 2021. Five-year graft survival after living compared with deceased donor transplant was 88.6% versus 80.7% for recipients aged 18-34 years, and 82.1% versus 68.0% for recipients aged 65 years or older. The total number of pediatric kidney transplants performed increased to 820 in 2021, the highest number since 2010. Despite numerous efforts, living donor kidney transplant remains low among pediatric recipients, with continued racial disparities. The rate of deceased donor transplants among pediatric candidates recovered in 2021 from a low in 2020. Congenital anomalies of the kidney and urinary tract remain the leading primary kidney disease diagnosis among pediatric candidates. Most pediatric deceased donor recipients receive a kidney from a donor with KDPI less than 35%. Graft survival continues to improve, with superior outcomes for living donor transplant recipients.

OPTN/SRTR 2021 Annual Data Report: Liver.

In 2021, liver transplant volume continued to grow, with a record 9,234 transplants performed in the United States, 8,665 (93.8%) from deceased donors and 569 (6.2%) from living donors. There were 8,733 (94.6%) adult and 501 (5.4%) pediatric liver transplant recipients. An increase in the number of deceased donor livers corresponded to an increase in the overall transplant rate and shorter waiting times, although still 10.0% of livers that were recovered were not transplanted. Alcohol-associated liver disease was the leading indication for both waitlist registration and liver transplant in adults, outpacing nonalcoholic steatohepatitis, while biliary atresia remained the leading indication for children. Related to allocation policy changes implemented in 2019, the proportion of liver transplants performed for hepatocellular carcinoma has decreased. Among adult candidates listed for liver transplant in 2020, 37.7% received a deceased donor liver transplant within 3 months, 43.8% within 6 months, and 53.3% within 1 year. Pretransplant mortality improved for children following implementation of acuity circle-based distribution. Short-term graft and patient survival outcomes up to 1 year worsened for adult deceased and living donor liver transplant recipients, which is a reversal of previous trends and coincided with the onset of the COVID-19 pandemic in early 2020. Longer-term outcomes among adult deceased donor liver transplant recipients were unaffected, with overall posttransplant mortality rates of 13.3% at 3 years, 18.6% at 5 years, and 35.9% at 10 years. Pretransplant mortality improved for children following implementation of acuity circle-based distribution and prioritization of pediatric donors to pediatric recipients in 2020. Pediatric living donor recipients had superior graft and patient survival outcomes compared with deceased donor recipients at all time points.

OPTN/SRTR 2021 Annual Data Report: Pancreas.

The number of pancreas transplants in the United States was largely unchanged in 2021 at 963 transplants compared with 962 in 2020, showing that recovery from the COVID-19 pandemic was not as pronounced in pancreas transplantation as in other organs. The number of simultaneous pancreas-kidney transplants (SPKs) decreased from 827 to 820, whereas the number of pancreas-after-kidney transplants and pancreas transplants alone increased marginally to compensate. The proportion of patients with type 2 diabetes on the waiting list increased to 22.9% in 2021, compared with 20.1% in 2020. Consequently, the proportion of transplants in patients with type 2 diabetes increased from 21.3% in 2020 to 25.9% in 2021. The proportion of transplants in older recipients (aged 55 years or older) also increased to 13.5% in 2021 from 11.7% in 2020. Outcomes after SPK continue to be the best of the three categories of pancreas transplants: 1-year graft failure for kidney at 5.7% and pancreas at 10.5% for transplants performed in 2020. The proportion of pancreas transplants performed by medium-volume centers (11-24 transplants per year) increased sharply to 48.3% in 2021 from 35.1% in 2020, with a corresponding decrease in transplants in large-volume centers (25 or more transplants per year) to 15.9% in 2021 from 25.7% in 2020.

Knowing When to Ignore the Numbers: Single-Center Experience Transplanting Deceased Donor Kidneys with Poor Perfusion Parameters.

BACKGROUND: Hypothermic machine perfusion is frequently used in evaluating marginal kidneys with poor perfusion parameters (PPP) contributing to delays in kidney placement or discard. We examined outcomes in deceased donor kidney transplants with PPP compared with those with optimal perfusion parameters (OPP). STUDY DESIGN: We conducted a retrospective single-center cohort study from 2001 to 2021 comparing PPP (n = 91) with OPP (n = 598) deceased donor kidney transplants. PPP was defined as terminal flow ≤80 mL/min and terminal resistance ≥0.40 mmHg/mL/min. OPP was defined as terminal flow ≥120 mL/min and terminal resistance ≤0.20 mmHg/mL/min. RESULTS: Mean terminal flow was PPP 66 ± 16 vs OPP 149 ± 21 mL/min and resistance was PPP 0.47 ± 0.10 vs OPP 0.15 ± 0.04 mmHg/mL/min (both p < 0.001). Donor age, donation after cardiac death, and terminal serum creatinine levels were similar between groups. Mean Kidney Donor Profile Index was higher among PPP donors (PPP 65 ± 23% vs OPP 52 ± 27%, p < 0.001). The PPP transplant group had more females and lower weight and BMI. Delayed graft function was comparable (PPP 32% vs OPP 27%, p = 0.33) even though cold ischemia times trended toward longer in PPP kidneys (PPP 28 ± 10 vs OPP 26 ± 9 hours, p = 0.09). One-year patient survival (PPP 98% vs OPP 97%, p = 0.84) and graft survival (PPP 91% vs OPP 92%, p = 0.23) were equivalent. PPP did predict inferior overall and death-censored graft survival long-term (overall hazard ratio 1.63, 95% CI 1.19 to 2.23 and death-censored hazard ratio 1.77, 95% CI 1.15 to 2.74). At 1 year, the estimated glomerular filtration rate was higher with OPP kidneys (PPP 40 ± 17 vs OPP 52 ± 19 mL/min/1.73 m 2 , p < 0.001). CONCLUSIONS: Short-term outcomes in PPP kidneys were comparable to OPP kidneys despite higher Kidney Donor Profile Index and longer cold ischemia times, suggesting a role for increased utilization of these organs with careful recipient selection.

1-Year Outcomes of Lung Transplantation for Coronavirus Disease 2019-Associated End-Stage Lung Disease in the United States.

BACKGROUND: Lung transplantation can provide quality of life and survival benefits for patients with coronavirus disease 2019 (COVID-19)-associated end-stage lung disease. Characteristics and outcomes of these lung transplant recipients are limited to mostly single-center experiences or provide a short-term follow-up. METHODS: Characteristics of deceased donors and adult lung transplant recipients for COVID-19-associated end-stage lung disease between August-2020 and June-2022 were analyzed using deidentified United Network for Organ Sharing database. Post-transplant patient survival of COVID-19 recipients was analyzed and compared with non-COVID-19 recipients. Secondary outcomes were length of hospitalization, post-transplant complications, and rates of organ rejection. RESULTS: During the study period, 400 lung transplants for COVID-associated end-stage lung disease comprised 8.7% of all lung transplants performed in United States. In the COVID-19 group, Hispanic males received lung transplants at significantly higher rates. The COVID-19 group was younger and had greater need for intensive care unit stay, mechanical ventilation, hemodialysis, extracorporeal membrane oxygenation support, and receipt of antibiotics pre-lung transplant. They had higher lung allocation score, with a shorter wait-list time and received more double lung transplants compared with non-COVID-19 recipients. Post-transplant, the COVID-19 cohort had longer hospital stays, with similar 1-year patient survival (COVID, 86.6% vs non-COVID, 86.3%). Post-transplant, COVID-19-associated deaths were 9.2% of all deaths among lung transplant recipients. CONCLUSIONS: Lung transplantation offers a effective option for carefully selected patients with end-stage lung disease from prior COVID-19, with short-term and long-term outcomes similar to those for lung transplant recipients of non-COVID-19 etiology.

Our Pediatric Liver and Kidney Transplant Activities in 2021.

OBJECTIVES: In children with end-stage renal disease, chronic liver failure, or acute liver failure, liver transplant and kidney transplant are the most effective modalities for better clinical outcomes compared with other therapies. However, children are particularly susceptible to surgical complications, so pediatric solid-organ transplants should be reserved for centers with substantial experience and multidisciplinary expertise. Here, we assessed liver and kidney transplants performed at our center in 2021. MATERIALS AND METHODS: From November 3, 1975, to December 31, 2021, we performed 701 liver transplants and 3290 kidney transplants. From January 1, 2021, to December 31, 2021, we performed 21 liver transplants (19 in children) and 114 kidney transplants (12 in children). We recorded age, sex, body mass index, comorbidities, etiologies, laboratory values, and clinical outcomes. RESULTS: For the year 2021, we performed 19 pediatric liver transplants and 12 pediatric kidney transplants. Mean age of liver recipients was 3.4 years, and 8 were male patients. The most common etiology was biliary atresia (n = 7). All liver grafts were from living related donors who were first-degree (n = 16) or second- degree (n = 3) relatives of the recipients. Mean hospital stay was 17.6 days. All but 2 liver transplant recipients were discharged successfully (2 died from sepsis in the early postoperative period). Mean age of kidney transplant recipients was 14.1 years, and 4 were male patients. The most common etiology was vesicoureteral reflux (n = 3). One kidney graft was from a deceased donor, with the rest from living related donors who were first-degree relatives of the recipients (n = 11; mother for 8 recipients and father for 3 recipients). Mean hospital stay was 4.3 days. All kidney transplant recipients were discharged successfully. CONCLUSIONS: Solid-organ transplants for young children are often complex but can be performed successfully at experienced transplant centers.

Early living donor liver transplantation for alcohol-associated hepatitis.

INTRODUCTION AND OBJECTIVES: Lately, there has been a steady increase in early liver transplantation for alcohol-associated hepatitis (AAH). Although several studies have reported favorable outcomes with cadaveric early liver transplantation, the experiences with early living donor liver transplantation (eLDLT) are limited. The primary objective was to assess one-year survival in patients with AAH who underwent eLDLT. The secondary objectives were to describe the donor characteristics, assess the complications following eLDLT, and the rate of alcohol relapse. MATERIALS AND METHODS: This single-center retrospective study was conducted at AIG Hospitals, Hyderabad, India, between April 1, 2020, and December 31, 2021. RESULTS: Twenty-five patients underwent eLDLT. The mean time from abstinence to eLDLT was 92.4 ± 42.94 days. The mean model for end-stage liver disease and discriminant function score at eLDLT were 28.16 ± 2.89 and 104 ± 34.56, respectively. The mean graft-to-recipient weight ratio was 0.85 ± 0.12. Survival was 72% (95%CI, 50.61-88) after a median follow-up of 551 (23-932) days post-LT. Of the 18 women donors,11 were the wives of the recipient. Six of the nine infected recipients died: three of fungal sepsis, two of bacterial sepsis, and one of COVID-19. One patient developed hepatic artery thrombosis and died of early graft dysfunction. Twenty percent had alcohol relapse. CONCLUSIONS: eLDLT is a reasonable treatment option for patients with AAH, with a survival of 72% in our experience. Infections early on post-LT accounted for mortality, and thus a high index of suspicion of infections and vigorous surveillance, in a condition prone to infections, are needed to improve outcomes.

Pancreas transplantation.

PURPOSE OF REVIEW: To define recent changes and future directions in the practice of pancreas transplantation (PT). Two major events have occurred in the past 18 months: COVID-19 pandemic, and the first world consensus conference on PT. Several innovative studies were published after the consensus conference. RECENT FINDINGS: During COVID-19 pandemic PT activity decreased. COVID-19 in transplant recipients increases mortality rates, but data from kidney transplantation show that mortality might be higher in waitlisted patients.The world consensus conference provided 49 jury deliberations on the impact of PT on management of diabetic patients and 110 practice recommendations.Recent evidence demonstrates that PT alone is safe and effective, that results of simultaneous pancreas and kidney (SPK) remain excellent despite older recipient age and higher prevalence of type 2 diabetes, that use of hepatitis C virus (HCV)-positive donors into HCV-negative recipients is associated with good outcomes, and that use of sirolimus as primary immunosuppressant and costimulation blockade does not improve results of SPK. SUMMARY: COVID-19 pandemic and the first world consensus conference on PT were major events. Although COVID-19 pandemic should not reduce PT activity in the future, a major positive impact on both volume and outcomes of PT is awaited from the proceedings of the world consensus conference.

Influenza Virus Infection and Transplantation.

Influenza infection poses significant risk for solid organ transplant recipients who often experience more severe infection with increased rates of complications, including those relating to the allograft. Although symptoms of influenza experienced by transplant recipients are similar to that of the general population, fever is not a ubiquitous symptom and lymphopenia is common. Annual inactivated influenza vaccine is recommended for all transplant recipients. Newer strategies such as using a higher dose vaccine or multiple doses in the same season appear to provide greater immunogenicity. Neuraminidase inhibitors are the mainstay of treatment and chemoprophylaxis although resistance may occur in the transplant setting. Influenza therapeutics are advancing, including the recent licensure of baloxavir; however, many remain to be evaluated in transplant recipients and are not yet in routine clinical use. Further population-based studies spanning multiple influenza seasons are needed to enhance our understanding of influenza epidemiology in solid organ transplant recipients. Specific assessment of newer influenza therapeutics in transplant recipients and refinement of prevention strategies are vital to reducing morbidity and mortality.

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

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

Optimal dose of rituximab in ABO-incompatible kidney transplantation in patients with low anti-A/B antibody titers: A single-center retrospective cohort study.

BACKGROUND: The clinical outcomes of ABO-incompatible (ABOi) kidney transplantation have improved with the introduction of desensitization therapy with rituximab. However, rituximab prevents not only antibody-mediated rejection (AMR) but also increases the risk of adverse events, such as infection. For ABOi kidney transplantation in patients with low anti-A/B antibody titers, we previously used a rituximab-free desensitization protocol and then initiated a single dose of 100 mg rituximab in 2016. We retrospectively compared the outcomes of ABOi kidney transplantation in patients with low anti-A/B antibody titers before and after the introduction of rituximab. METHODS: ABOi kidney transplantations (n = 142) in patients with low anti-A/B antibody titers between 2007 and 2021 were included. Patients were divided into two groups (with and without rituximab) for desensitization. The primary outcomes were the incidence of acute AMR and infection. RESULTS: Sixty-six patients were desensitized without rituximab (rituximab-free group), and 76 were pretreated with 100 mg rituximab (rituximab group) before transplantation. The incidence of acute AMR was significantly lower in the rituximab group than in the rituximab-free group (.0% [0/76] vs. 7.6% [5/66], respectively; p = .047). Post-transplantation anti-A/B antibody titers were also lower in the rituximab group than in the rituximab-free group. There was no significant difference in the incidence of adverse events, including infections, between the two groups. CONCLUSION: In ABOi kidney transplantation patients with low anti-A/B antibody titers, the desensitization protocol with a single dose of 100 mg rituximab was effective in preventing acute AMR without increasing the risk of other adverse events.

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.

The 2022 International Pancreas Transplant Registry Report-A Review.

Over the last decades, the number of pancreas transplants has increased all over the world. Since the first pancreas transplant in 1966, patient and graft survival after simultaneous pancreas and kidney as well as after solitary pancreas transplantation have improved significantly. Patient survival at 1 year is >96% in all 3 recipient categories and pancreas graft survival is >90% for simultaneous pancreas and kidney and >86% for solitary transplants. For transplants performed between 2001 and 2010, with >10 years' follow-up time, the half-life (50% graft function) was 13 years for simultaneous pancreas and kidney, almost 10 years for a pancreas after kidney transplant, and >6 years for a pancreas transplant alone. These excellent results are even more astonishing because more high-risk patients were transplanted. The main reasons for improvement in outcome were reductions in technical failures and immunologic graft losses. These decreases were due to better patient and donor selection, standardization of surgical techniques, and superior immunosuppressive protocols.

Organ transplantation using COVID-19-positive deceased donors.

The COVID-19 pandemic has influenced organ transplantation decision making. Opinions regarding the utilization of coronavirus disease-2019 (COVID-19) donors are mixed. We hypothesize that COVID-19 infection of deceased solid organ transplant donors does not affect recipient survival. All deceased solid organ transplant donors with COVID-19 testing results from March 15, 2020 to September 30, 2021 were identified in the OPTN database. Donors were matched to recipients and stratified by the COVID-19 test result. Outcomes were assessed between groups. COVID-19 test results were available for 17 694 donors; 150 were positive. A total of 269 organs were transplanted from these donors, including 187 kidneys, 57 livers, 18 hearts, 5 kidney-pancreases, and 2 lungs. The median time from COVID-19 testing to organ recovery was 4 days for positive and 3 days for negative donors. Of these, there were 8 graft failures (3.0%) and 5 deaths (1.9%). Survival of patients receiving grafts from COVID-19-positive donors is equivalent to those receiving grafts from COVID-19-negative donors (30-day patient survival = 99.2% COVID-19 positive; 98.6% COVID-19 negative). Solid organ transplantation using deceased donors with positive COVID-19 results does not negatively affect early patient survival, though little information regarding donor COVID-19 organ involvement is known. While transplantation is feasible, more information regarding COVID-19-positive donor selection is needed.

ABO-Incompatible Living Donor Liver Transplant From a Blood Type A2 Donor to a Type B Recipient: A Note of Caution.

Standardization of immunomodulation protocols has enabled ABO-incompatible liver transplants with outcomes similar to those of ABO-compatible liver transplants. Patients with the A2 blood group are unique because they have a diminished expression of the A antigen. Despite rare immune complications, this phenomenon of diminished expression has led to treatment of type A2 donors according to the regimen for type O blood group donors in ABO-incompatible liver transplants. Additionally, the requirement for pretransplant recipient immunomodulation is consi dered minimal when considering these donors. The transplant of a type A2 donor kidney to a type B recipient is well recognized; however, for liver donation the A2-to-B transplant is rare. Here, we present a case of 48-year-old male patient with blood group type B who underwent ABO-incompatible liver transplant of a right lobe liver graft from a type A2 donor. Postoperatively, despite adequate immunosuppression and initiation of thera - peutic plasma exchange, the patient developed severe and refractory antibody-mediated rejection that ultimately abated with a splenectomy. This report highlights the low but tangible risk of antibody-mediated rejection in ABO-incompatible liver transp lants from type A2 donors and emphasizes the importance of serial monitoring of anti-A isohemag glutinin titers and posttransplant splenectomy to ensure that liver grafts with antibody-mediated rejection can be rescued.

Association between PIRCHE-II scores and de novo allosensitization after reduction of immunosuppression during SARS-CoV-2 infection in kidney transplant recipients.

BACKGROUND: Before the availability of mRNA vaccines, many transplant centers chose to significantly reduce maintenance immunosuppression in kidney transplant recipients (KTRs) with SARS-CoV-2 infection. The extent to which this increases the risk of allosensitization is unclear. METHODS: In this observational cohort study, we analyzed 47 KTRs from March 2020 to February 2021 who underwent substantial reduction of maintenance immunosuppression during SARS-CoV-2 infection. KTRs were followed at 6 and 18 months concerning the development of de novo donor-specific anti-HLA (human leukocyte antigen) antibodies (DSA). The HLA-derived epitope mismatches were calculated using the predicted indirectly recognizable HLA-epitopes (PIRCHE-II) algorithm. RESULTS: In total, 14 of 47 KTRs (30%) developed de novo HLA antibodies after the reduction of maintenance immunosuppression. KTRs with higher total PIRCHE-II scores and higher PIRCHE-II scores for the HLA-DR locus were more likely to develop de novo HLA antibodies (p = .023, p = .009). Furthermore, 4 of the 47 KTRs (9%) developed de novo DSA after reduction of maintenance immunosuppression, which were exclusively directed against HLA-class II antigens and also showed higher PIRCHE-II scores for HLA-class II. The cumulative mean fluorescence intensity of 40 KTRs with preexisting anti-HLA antibodies and 13 KTRs with preexisting DSA at the time of SARS-CoV-2 infection remained stable after the reduction of maintenance immunosuppression (p = .141; p = .529). CONCLUSIONS: Our data show that the HLA-derived epitope mismatch load between donor and recipient influences the risk of de novo DSA development when immunosuppression is temporarily reduced. Our data further suggest that reduction in immunosuppression should be made more cautiously in KTRs with high PIRCHE-II scores for HLA-class II antigens.