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.

COVID-19 Vaccination Status and Operative Outcomes after Kidney Transplantation.

BACKGROUND: Kidney transplantation remains the best available treatment for end-stage renal disease. However, promoting graft longevity and preventing allosensitization requires strict adherence with a stringent immunosuppression regimen. The COVID-19 pandemic has offered new challenges for kidney transplant patients and many transplant centers are denying transplantation to unvaccinated patients. The aim of this study was to evaluate whether unvaccinated patients had inferior adherence after kidney transplantation along with a reduction in graft survival. STUDY DESIGN: Patients undergoing a deceased donor kidney transplantation at a single academic medical center from February 2021 to May 2022 were retrospectively reviewed. February 2021 was chosen as the start date for record review because it was 3 months after the first COVID-19 vaccination was authorized for emergency use. Patients were considered to be vaccinated if they received at least 1 dose of any mRNA vaccine by their transplantation date. RESULTS: Of the 301 patients who met study criteria, 234 were vaccinated and 67 were unvaccinated. Cohorts stratified by vaccination status were well matched. Younger age was an independent risk factor for nonvaccination. Interestingly, unvaccinated patients had worse postoperative adherence with a greater average number of missed postoperative clinic visits (p = 0.03) and a strong trend toward missing 3 or more postoperative clinic visits (p = 0.07). Finally, unvaccinated patients had statistically more subtherapeutic tacrolimus troughs (p = 0.01). CONCLUSIONS: Patients not vaccinated against COVID-19 had higher rate of postoperative nonadherence in key areas of immunosuppression monitoring and clinic visit attendance. Providers should be cognizant that an unvaccinated status may be a harbinger for poor adherence; therefore, stricter strategies for patient outreach are critical to ensure graft success in this vulnerable patient population.

International Practices on COVID-19 Vaccine Mandates for Transplant Candidates.

Background: The coronavirus disease 2019 (COVID-19) pandemic created unprecedented challenges for solid organ transplant centers worldwide. We sought to assess an international perspective on COVID-19 vaccine mandates and rationales for or against mandate policies. Methods: We administered an electronic survey to staff at transplant centers outside the United States (October 14, 2021-January 28, 2022) assessing the reasons cited by transplant centers for or against implementing a COVID-19 vaccine mandate. Each responding center was represented once in the analysis. Results: Respondents (N=90) represented 27 countries on five continents. Half (51%) of responding transplant center representatives reported implementing a COVID-19 vaccine mandate, 38% did not, and 12% were unsure. Staff at centers implementing a vaccine mandate cited efficacy of pretransplant vaccination versus post-transplant vaccination, importance for public health, and minimizing exposure of other patients as rationale for the mandate. Of centers with a mandate, the majority (81%) of the centers mandate vaccination regardless of prior SARS-CoV-2 infection status and regardless of prevaccination spike-protein antibody titer or other markers of prior infection. Only 27% of centers with a vaccine mandate for transplant candidates also extended a vaccine requirement to living donor candidates. Centers not implementing a vaccine mandate cited concerns for undue pressure on transplant candidates, insufficient evidence to support vaccine mandates, equity, and legal considerations. Conclusions: The approach to pretransplant COVID-19 vaccination mandate policies at international transplant centers is heterogeneous. International transplant centers with a vaccine mandate were more willing to extend vaccine requirements to candidates' support persons, cohabitants, and living donors. Broader stakeholder engagement to overcome vaccine hesitancy across the world is needed to increase the acceptance of pretransplant COVID-19 vaccination to protect the health of transplant patients.

Exacerbation of Racial Disparities in Living Donor Kidney Transplantation During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic profoundly impacted transplant services, with a particularly strong impact on living donor kidney transplantation.The COVID-19 pandemic appears to have disproportionately impacted Black patients' access to living donor kidney transplantation.As the pandemic evolves through surges and vaccine acceptance disparities persist, ongoing attention to transplant disparities is needed.

Survey of current transplant center practices regarding COVID-19 vaccine mandates in the United States.

An electronic survey canvassing current policies of transplant centers regarding a COVID-19 vaccine mandate for transplant candidates and living donors was distributed to clinicians at US solid organ transplant centers performing transplants from October 14, 2021-November 15, 2021. Responses were received from staff at 141 unique transplant centers. These respondents represented 56.4% of US transplant centers, and responding centers performed 78.5% of kidney transplants and 82.4% of liver transplants in the year prior to survey administration. Only 35.7% of centers reported implementing a vaccine mandate, while 60.7% reported that vaccination was not required. A minority (42%) of responding centers with a vaccine mandate for transplant candidates also mandated vaccination for living organ donors. Centers with a vaccine mandate most frequently cited clinical evidence supporting the efficacy of pre-transplant vaccination (82%) and stewardship obligations to ensure organs were transplanted into the lowest risk patients (64%). Centers without a vaccine mandate cited a variety of reasons including administrative, equity, and legal considerations for their decision. Transplant centers in the United States exhibit significant heterogeneity in COVID-19 vaccination mandate policies for transplant candidates. While all centers encourage vaccination, most centers have not mandated COVID-19 vaccination for candidates and living donors, citing administrative opposition, legal prohibitions, and concern about equity in access to transplants.

COVID-19 vaccination timing and kidney transplant waitlist management: An international perspective.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs worldwide. The aim of this study is to assess an international perspective on challenges faced by kidney transplant programs. METHODS: We administered an electronic survey instrument from January 3, 2021 to June 8, 2021 to staff at transplant programs outside the United States that comprised of 10 questions addressing the management of kidney transplant candidates with asymptomatic COVID-19 infection or unvaccinated who receive an organ offer. RESULTS: Respondents (n = 62) represented 19 countries in five continents. Overall, 90.3% of respondents encourage vaccination on the waiting list and prior to planned living donor transplant. Twelve percent of respondents reported that they have decided to inactivate unsensitized candidates (calculated panel reactive antibody, cPRA <80%) until they received the two doses of vaccination, and 7% report inactivating candidates who have received their first vaccine dose pending receipt of their second dose. The majority (88.5%) of international respondents declined organs for asymptomatic, nucleic acid testing (NAT)+ patients during admission without documented prior infection. However, 22.9% of international respondents proceeded with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. CONCLUSIONS: Practitioners in some countries are less willing to accept deceased donor organs for waitlist candidates with incomplete COVID-19 vaccination status and to wait longer before scheduling living donor transplant, compared to United States practices. Access to vaccinations and other resources may contribute to these differences. More research is needed to guide the optimal approach to vaccination before and after transplant.

Operational challenges in the COVID-19 era: Asymptomatic infections and vaccination timing.

The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid testing (NAT) for SARS-CoV-2 is unclear, as this result may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of robust outcomes data, transplant professionals at US adult kidney transplant centers were surveyed (February 13, 2021 to April 29, 2021) to determine community practice (N: 92 centers, capturing 41% of centers and 57% of transplants performed). The majority (97%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 32% of centers proceed with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with kidney transplant in patients with positive SARS-CoV-2 NAT results due to presumed viral shedding. Furthermore, few centers are requiring COVID-19 vaccination prior to transplantation at this time.

COVID-19 test result reporting for deceased donors: Emergent policies, logistical challenges, and future directions.

The coronavirus disease 2019 (COVID-19) pandemic poses unprecedented challenges to the transplant community, including organ procurement organizations (OPOs), transplant centers, regulatory agencies, and recipient candidates. Access to timely, accurate information on the status of deceased donor viral infection is essential in determining organ acceptance. The Organ Procurement and Transplantation Network expeditiously added fields to collect these data; however, use of the data collection fields was not uniform nationally. Standardized, field-defined data capture and reporting are vital to ensure optimal organ utilization during this pandemic, and to prepare the community for subsequent challenges.

Hydroxychloroquine and maintenance immunosuppression use in kidney transplant recipients: Analysis of linked US registry and claims data.

Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory effects used to treat systemic lupus erythematosus (SLE) and scleroderma. The antiviral effects of HCQ have raised attention in the context of the COVID-19 pandemic, although safety is controversial. We examined linkages of national transplant registry data with pharmaceutical claims and Medicare billing claims to study HCQ use among Medicare-insured kidney transplant recipients with SLE or scleroderma (2008-2017; N = 1820). We compared three groups based on immunosuppression regimen 7 months-to-1 year post transplant: (a) tacrolimus (Tac) + mycophenolic acid (MPA) + prednisone (Pred) (referent group, 77.7%); (b) Tac + MPA + Pred + HCQ (16.5%); or (c) other immunosuppression + HCQ (5.7%). Compared to the referent group, recipients treated with other immunosuppression + HCQ had a 2-fold increased risk of abnormal ECG or QT prolongation (18.9% vs. 10.7%; aHR,1.12 1.963.42 , p = .02) and ventricular arrhythmias (15.2% vs. 11.4%; aHR,1.00 1.813.29 , p = .05) in the >1-to-3 years post-transplant. Tac + MPA + Pred + HCQ was associated with increased risk of ventricular arrhythmias (13.5% vs. 11.4%; aHR,1.02 1.542.31 , p = .04) and pancytopenia (35.9% vs. 31.4%; aHR,1.03 1.311.68 , p = .03) compared to triple immunosuppression without HCQ. However, HCQ-containing regimens were not associated with an increased risk of death or graft failure. HCQ may be used safely in selected kidney transplant recipients in addition to their maintenance immunosuppression, although attention to arrhythmias is warranted.