Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience.

BACKGROUND: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft. METHODS: We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function. RESULTS: There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m 2 . Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases. CONCLUSIONS: The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients.

Outcomes of Renal Transplant Recipients With SARS-CoV-2 Infection in the Eye of the Storm: A Comparative Study With Waitlisted Patients.

BACKGROUND: Patients with chronic kidney disease stage 5 and those on immunosuppression are particularly vulnerable and are shielded as per public health strategy. We present our experience of coronavirus disease 2019 (COVID-19) transplant patients in one of the most affected parts of the UK with direct comparison to waitlisted patients. METHODS: A single-center prospective study of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive waitlisted and transplant patients was undertaken to compare these groups and assess clinical outcomes. RESULTS: A total of 60 consecutive symptomatic SARS-CoV-2 positive patients were identified with 32 active waitlisted patients and 28 functioning renal transplants. Demographics were similar. The incidence of symptomatic COVID-19 in the waitlisted group was 9.9% compared to 1.9% in renal transplant patients (P < 0.001). Immunosuppression did not influence initial symptomology. Fifteen percent of patients in the waitlisted and 32% in the transplant groups died (P = 0.726). Mortality as proportion of total waitlisted (321 patients) and transplant population (1434 patients) of our centre was 1.5% and 0.6% (P < 0.001), respectively. C-reactive protein (CRP) at 48 h and peak CRP were associated with mortality in both groups while quick sequential organ failure assessment score at 48 h (P = 0.036) was associated with mortality for transplant patients. CONCLUSIONS: Incidence of COVID-19 is higher in the waitlisted population but transplant patients have more severe disease, reflected by higher mortality. CRP at 48 h can be used as a predictive tool. In the absence of effective treatments, the current strategy of shielding is arguably the most important factor in protecting patients while resuming transplantation.

Mortality Rates in Transplant Recipients and Transplantation Candidates in a High-prevalence COVID-19 Environment.

BACKGROUND: The risk of COVID-19 infection in transplant recipients (TRs) is unknown. Patients on dialysis may be exposed to greater risk of infection due to an inability to isolate. Consideration of these competing risks is important before restarting suspended transplant programs. This study compared outcomes in kidney and kidney/pancreas TRs with those on the waiting list, following admission with COVID-19 in a high-prevalence region. METHODS: Audit data from all 6 London transplant centers were amalgamated. Demographic and laboratory data were collected and outcomes included mortality, intensive care (ITU) admission, and ventilation. Adult patients who had undergone a kidney or kidney/pancreas transplant, and those active on the transplant waiting list at the start of the pandemic were included. RESULTS: One hundred twenty-one TRs and 52 waiting list patients (WL) were admitted to hospital with COVID-19. Thirty-six TR died (30%), while 14 WL patients died (27% P = 0.71). There was no difference in rates of admission to ITU or ventilation. Twenty-four percent of TR required renal replacement therapy, and 12% lost their grafts. Lymphocyte nadir and D-dimer peak showed no difference in those who did and did not die. No other comorbidities or demographic factors were associated with mortality, except for age (odds ratio of 4.3 [95% CI 1.8-10.2] for mortality if aged over 60 y) in TR. CONCLUSIONS: TRs and waiting list patients have similar mortality rates after hospital admission with COVID-19. Mortality was higher in older TRs. These data should inform decisions about transplantation in the COVID era.

Behaviour of transplanted tumours and role of matching in rejection.

BACKGROUND: Tumour transfer/development is one of the more serious risks associated with transplantation. The behaviour of a tumour can be unpredictable in immunosuppressed recipients. We report a highly sensitive method to monitor tumour behaviour in real time in a rodent tumour transplant model. This paper also explores the effect of MHC matching on tumour growth among control and immunosuppressed hosts. METHODS: Luciferase expressing Wistar rat kidney tumour cells were transplanted into either Wistar or Lewis recipients which mimic a well and poorly matched combination to assess the effects of MHC matching on transplanted tumour cells. Experimental groups included controls with no immunosuppression and animals immunosuppressed with cyclosporine. The latter group was further divided into a continuous treatment group which received four weeks of immunosuppression and a treatment withdrawal group where immunosuppression was stopped after two weeks to assess the effects of rejection on tumour growth. RESULTS: All the tumour cells were rejected in the control animals that received no immunosuppression, within 2 weeks among well-matched combination and within one week in the poorly matched combination (p 0.001). The transplanted tumour cells continued to grow in both well-matched and poorly matched groups who were treated with cyclosporine, but growth was significantly faster in the well-matched combination (p 0.033). After treatment withdrawal the tumour cells were rejected in all the animals of the poorly matched group compared to 50% in well matched animals within the four-week study period (p 0.039). CONCLUSION: In the absence of immunosuppression the hosts reject the transplanted tumour cells, and the anti-tumour response is stronger when there is a greater mismatch in MHC with the recipient. In the presence of cyclosporine immunosuppression the tumour continues to grow, however, after withdrawal of the immunosuppression, tumour clearance is quicker in the poorly matched background. This data supports the idea of expansion of the donor pool by using kidneys after ex vivo resection of small renal tumours and that these organs should be transplanted into a less well-matched HLA recipient. We hypothesise that should a tumour recurrence occur a poorly matched recipient could clear the tumour through withdrawal of immunosuppression.

Development of an ex vivo technique to achieve reanimation of hearts sourced from a porcine donation after circulatory death model.

BACKGROUND: This study reports on the development of a novel method for achieving ex vivo reanimation of hearts from a porcine donation after circulatory death (DCD) model without the use of donor pretreatment. METHODS: Porcine hearts (n = 23) were procured 10-29 min after confirmation of asystole. All hearts underwent initial flush with AQIX RS-I solution (London, UK). A 2-h preservation period followed: group 1 hearts (n1-n11) were preserved using static cold storage, group 2 hearts (n12-n17) were preserved using oxygenated, hypothermic machine perfusion (MP), and group 3 hearts (n18-n23) were subjected to retrograde oxygen persufflation. Reperfusion was performed on a Langendorff modification of a Model 33 Functional Circulation circuit. In hearts n16-n23, a dialysis circuit was incorporated into the circuit to facilitate removal of metabolites. The experimental protocol was allowed to follow an evolutionary course, with the aim of achieving greater success with reanimation. RESULTS: In group 1 (static cold storage), 7 of the 11 hearts (63.6%) achieved reanimation on the ex vivo circuit. Two of the six hearts (33.3%) in group 2 (MP) were successfully reanimated. All the six hearts (100%) in group 3 (persufflation) were successfully reanimated. The period of sustained reanimation increased when dialysis was incorporated into the circuit with a maximum of 300 min. CONCLUSIONS: Porcine DCD hearts after 29 min of warm ischemia can be reanimated using the method described. A mechanism of reoxygenation (oxygenated MP or coronary sinus oxygen persufflation) during preservation appears mandatory for hearts from DCDs. Persufflation was associated with a higher probability of successful reanimation. Dialysis in the warm phase was useful in removing metabolites that could interfere with reanimation. The results demonstrate the potential of DCDs to counter the decline affecting heart transplantation.