The minimum weight and age of kidney donors: en bloc kidney transplantation from preterm neonatal donors weighing less than 1.2 kg to adult recipients.

En bloc kidney transplantation (EBKT) to adults from preterm neonates following donation after circulatory death has not been described in the literature. We report 2 successful cases of EBKT from preterm neonatal donation after circulatory death donors weighing <1.2 kg to adult recipients. The first case was a preterm female infant born at 29 weeks' gestational age, weighing 1.07 kg. The recipient was a 34-year-old woman weighing 75 kg. At the 9-month follow-up, the patient demonstrated excellent graft function with a creatinine concentration of 1.48 mg/dL. The second donor was a preterm female infant born at 29 weeks and 5 days' gestation, weighing 1.17 kg. The recipient was a 25-year-old woman weighing 46 kg. By 5 months post surgery, the serum creatinine level had gradually decreased to 1.47 mg/dL. In our experience, EBKT from preterm neonates <30 weeks' gestation and weighing <1.2 kg has demonstrated acceptable short- to medium-term results.

Impact of ex vivo lung perfusion on brain-dead donor lung utilization: The French experience.

Ex vivo lung perfusion (EVLP) is a valuable method for expanding the lung donor pool. Its indications currently differ across centers. This national retrospective cohort study aimed to describe the profile of donors with lungs transplanted after EVLP and determine the effectiveness of EVLP on lung utilization. We included brain-dead donors with at least one lung offered between 2012 and 2019 in France. Lungs transplanted without or after EVLP were compared with those that were rejected. Donor group phenotypes were determined with multiple correspondence analysis (MCA). The association between donor factors and lung transplantation was assessed with a multivariable multinomial logistic regression. MCA revealed that donors whose lungs were transplanted after EVLP had profiles similar to the donors whose lungs were declined and quite different from those of donors with lungs transplanted without EVLP. Donor predictors of graft nonuse included age ≥50 years, smoking history, PaO2 /FiO2 ratio ≤300 mmHg, abnormal chest imaging, and purulent secretions. EVLP increased utilization of lungs from donors with a smoking history, PaO2 /FiO2 ratio ≤300 mmHg, and abnormal chest imaging.

Liver transplantation performed in a SARS-CoV-2 positive hospitalized recipient using a SARS-CoV-2 infected donor.

The coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 currently affected more than 108 million people worldwide with a fatality rate of 2.2%. Herein, we report the first case of liver transplantation (LT) performed with a liver procured from a SARS-CoV-2 positive donor. The recipient was a 35-year-old SARS-CoV-2 positive female patient affected by severe end-stage HBV-HDV-related liver disease (model of end-stage liver disease = 32) who had neutralizing SARS-CoV-2 antibodies (titers 1:320) at time of LT. The LT was successful, and the graft is functioning two months after surgery. The recipient cleared the SARS-CoV-2 infection 1 month after LT. The current case shows that the prompt use of SARS-CoV-2 infected liver donors offers an invaluable life-saving opportunity for SARS-CoV-2 positive wait-listed patients who developed neutralizing SARS-CoV-2 antibodies.

Fatal diffuse pulmonary fat microemboli following reperfusion in liver transplantation with the use of marginal steatotic allografts.

Organ shortage is a major cause of delayed liver transplantation and increased waitlist time. The level of donor steatosis is a significant determinant in organ selection. Scarcity of organs has led some programs to expand their acceptable criteria for the percentage of steatosis. We report two cases of liver transplantation of steatotic donor organs that resulted in mortality within hours from transplantation. Postmortem analysis showed evidence of diffuse pulmonary fat microemboli likely originating from the donor organ, with marked preservation reperfusion injury. The mechanism of diffuse fat microemboli in this setting and possible relationship to other perioperative syndromes (transfusion-related lung injury, acute kidney injury, and postreperfusion syndrome) is discussed.

The impact of postreperfusion syndrome during liver transplantation using livers with significant macrosteatosis.

The impact of postreperfusion syndrome (PRS) during liver transplantation (LT) using donor livers with significant macrosteatosis is largely unknown. Clinical outcomes of all patients undergoing LT with donor livers with moderate macrosteatosis (30%-60%) (N = 96) between 2000 and 2017 were compared to propensity score matched cohorts of patients undergoing LT with donor livers with mild macrosteatosis (10%-29%) (N = 96) and no steatosis (N = 96). Cardiac arrest at the time of reperfusion was seen in eight (8.3%) of the patients in the moderate macrosteatosis group compared to one (1.0%) of the patients in the mild macrosteatosis group (P = .02) and zero (0%) of the patients in the no steatosis group (P = .004). Patients in the moderate macrosteatosis group had a higher rate of PRS (37.5% vs 18.8%; P = .004), early allograft dysfunction (EAD) (76.4% vs 25.8%; P < .001), renal dysfunction requiring continuous renal replacement therapy following transplant (18.8% vs 8.3%; P = .03) and return to the OR within 30 days (24.0% vs 7.3%; P = .002), than the no steatosis group. Both long-term patient (P = .30 and P = .08) and graft survival (P = .15 and P = .12) were not statistically when comparing the moderate macrosteatosis group to the mild macrosteatosis and no steatosis groups. Recipients of LT using livers with moderate macrosteatosis are at a significant increased risk of PRS. If patients are able to overcome the initial increased perioperative risk of using these donor livers, long-term graft survival does not appear to be different than matched recipients receiving grafts with no steatosis.

Alemtuzumab induction and belatacept maintenance in marginal pathology renal allografts.

We performed a prospective, 12-month, single-center, nonrandomized, open-label pilot study to investigate the use of belatacept therapy combined with alemtuzumab induction in renal allografts with preexisting pathology, as these kidneys may be more susceptible to additional toxicity when exposed to calcineurin inhibitors posttransplant. Nineteen belatacept recipients were matched retrospectively to a cohort of tacrolimus recipients on the basis of preimplantation pathology. The estimated glomerular filtration rate was not significantly different between belatacept and tacrolimus recipients at either 3 or 12 months posttransplant (59 vs 45, P = 0.1 and 56 vs 48 mL/min/1.72/m2 , P = 0.3). Biopsy-proven acute rejection rates at 12 months were 26% in belatacept recipients and 16% in tacrolimus recipients (P = 0.7). Graft survival at 1 year was 89% in both groups. Alemtuzumab induction combined with either calcineurin inhibitor or costimulatory blockade therapies resulted in similar acceptable one-year outcomes in kidneys with preexisting pathologic changes. Longer-term follow-up may be necessary to identify preferential strategies to improve outcomes of kidneys at a higher risk for poor function (ClinicalTrials.gov-NCT01496417).

UK registry analysis of donor substance misuse and outcomes following pancreas transplantation.

Substance abuse is unfortunately common in organ donors. Often, these organs are declined for transplant, not only because of concerns around blood-borne virus transmission but also because of perceived poor outcomes. In kidney transplantation, previous studies have demonstrated donor smoking status significantly impacts transplant outcome, but intravenous drug use or alcohol dependence does not. This study aims to clarify these issues in pancreas transplantation. Retrospective data on all UK solid organ pancreas transplants from 1994 to 2015 were obtained from the NHSBT UK Transplant Registry. The impact of illicit drug misuse, alcohol abuse, and smoking on graft and patient survival were analyzed using Kaplan-Meier plots and a Cox regression model. A total of 1175 of the 2317 (49.5%) donors were categorized as substance misusers. Univariate survival analysis revealed no significant impact of substance misuse on 10-year graft or patient survival. Multivariate analysis confirmed substance misuse was not associated with impaired graft or patient survival. A history of donor substance misuse does not negatively impact 10-year graft or patient survival following pancreas transplantation. This is a large national registry analysis with long-term follow-up data and should therefore provide clinicians with reassurance when considering pancreas grafts from substance misuse donors.

Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution.

Ex situ dual hypothermic oxygenated machine perfusion (DHOPE) and normothermic machine perfusion (NMP) of donor livers may have a complementary effect when applied sequentially. While DHOPE resuscitates the mitochondria and increases hepatic adenosine triphosphate (ATP) content, NMP enables hepatobiliary viability assessment prior to transplantation. In contrast to DHOPE, NMP requires a perfusion solution with an oxygen carrier, for which red blood cells (RBC) have been used in most series. RBC, however, have limitations and cannot be used cold. We, therefore, established a protocol of sequential DHOPE, controlled oxygenated rewarming (COR), and NMP using a new hemoglobin-based oxygen carrier (HBOC)-based perfusion fluid (DHOPE-COR-NMP trial, NTR5972). Seven livers from donation after circulatory death (DCD) donors, which were initially declined for transplantation nationwide, underwent DHOPE-COR-NMP. Livers were considered transplantable if perfusate pH and lactate normalized, bile production was ≥10 mL and biliary pH > 7.45 within 150 minutes of NMP. Based on these criteria five livers were transplanted. The primary endpoint, 3-month graft survival, was a 100%. In conclusion, sequential DHOPE-COR-NMP using an HBOC-based perfusion fluid offers a novel method of liver machine perfusion for combined resuscitation and viability testing of suboptimal livers prior to transplantation.

Renal transplant from infant and neonatal donors is a feasible option for the treatment of end-stage renal disease but is associated with increased early graft loss.

Kidney transplants from young pediatric donors are uncommonly performed in the UK. Published literature of kidney transplant from donors weighing less than 5 kg is sparse. We present our initial experience of en bloc kidney transplantation (EKT) from donors weighing less than 20 kg, including neonatal donors. All recipients undergoing EKT from donors under 20 kg at our center from January 2005 to October 2016 were included. Donor and recipient details were recorded from a prospective database. Electronic patient records were examined for follow-up data. Of 30 EKTs included, 15 were from ≤5 kg donors and 15 from >5 kg donors (median weight 3.4 and 12.7 kg, respectively). One-year graft survival for ≤5 kg and >5 kg donors for EKT was 86.7% and 93.3% (P = 0.85), respectively. Progressive improvement in estimated GFR (eGFR) was noted in both donor categories through first-year posttransplant but in the ≤5 kg donor category significant improvement was seen at 12 months compared to 3 months after transplantation (median eGFR 37.3 vs 70.0 mL/min/1.73 m2 , P = 0.03). Two early graft losses were attributable to early vascular complications and one graft loss due to primary nonfunction. Our data show that kidney transplantation from such donors is a feasible option at centers with experience of EKT, albeit with increased risk of early graft loss.

Outcomes of organ transplants when the donor is a prior recipient.

Organ shortage continues to challenge the field of transplantation. One potential group of donors are those who have been transplant recipients themselves, or Organ Donation After Transplant (ODAT) donors. We conducted a retrospective cohort study to describe ODAT donors and to compare outcomes of ODAT grafts versus conventional grafts. From October 1, 1987 to June 30, 2015, 517 former recipients successfully donated 803 organs for transplant. Former kidney recipients generally survived a median of approximately 4 years before becoming an ODAT donor whereas liver, lung, and heart recipients generally survived less than a month prior to donation. In the period June 1, 2005 to December 31, 2014, liver grafts from ODAT donors had a significantly higher risk of graft failure compared to non-ODAT liver transplants (P = .008). Kidney grafts donated by ODAT donors whose initial transplant occurred >1 year prior were associated with significantly increased graft failure (P = .012). Despite increased risk of graft failure amongst certain ODAT grafts, 5-year survival was still high. ODAT donors should be considered another form of expanded criteria donor under these circumstances.

Resolution of donor non-alcoholic fatty liver disease following liver transplantation.

INTRODUCTION: Transplant surgeons conventionally select against livers displaying high degrees (>30%) of macrosteatosis (MaS), out of concern for primary non-function or severe graft dysfunction. As such, there is relatively limited experience with such livers, and the natural history remains incompletely characterized. We present our experience of transplanted livers with high degrees of MaS and microsteatosis (MiS), with a focus on the histopathologic and clinical outcomes. METHODS: Twenty-nine cases were identified with liver biopsies available from both the donor and the corresponding liver transplant recipient. Donor liver biopsies displayed either MaS or MiS ≥15%, while all recipients received postoperative liver biopsies for cause. RESULTS: The mean donor MaS and MiS were 15.6% (range 0%-60%) and 41.3% (7.5%-97.5%), respectively. MaS decreased significantly from donor (M=15.6%) to recipient postoperative biopsies (M=0.86%), P<.001. Similarly, MiS decreased significantly from donor biopsies (M=41.3%) to recipient postoperative biopsies (M=1.8%), P<.001. At a median of 68 days postoperatively (range 4-384), full resolution of MaS and MiS was observed in 27 of 29 recipients. CONCLUSIONS: High degrees of MaS and MiS in donor livers resolve in recipients following liver transplantation. Further insight into the mechanisms responsible for treating fatty liver diseases could translate into therapeutic targets.

Impact of Subnormothermic Machine Perfusion Preservation in Severely Steatotic Rat Livers: A Detailed Assessment in an Isolated Setting.

The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS). The fatty livers were retrieved and preserved for 4 h using either CS in histidine-tryptophan-ketoglutarate or SMP in polysol solution. Graft functional integrity was evaluated via oxygenated ex vivo reperfusion for 2 h at 37°C. SMP resulted in significant reductions in not only parenchymal alanine aminotransferase (p < 0.001), but also mitochondrial glutamate dehydrogenase (p < 0.001) enzyme release. Moreover, portal venous pressure (p = 0.047), tissue adenosine triphosphate (p = 0.001), bile production (p < 0.001), high-mobility group box protein-1 (p < 0.001), lipid peroxidation, and tissue glutathione were all significantly improved by SMP. Electron microscopy revealed that SMP alleviated deleterious alterations of sinusoidal microvasculature and hepatocellular mitochondria, both of which are characteristic disadvantages associated with steatosis. SMP could protect 50-60% macrosteatotic livers from preservation/reperfusion injury, and may thus represent a new means for expanding available donor pools.

Th-17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney Transplants Using Extended Criteria Donors During Acute T Cell-Mediated Rejection.

Although renal transplantation using expanded criteria donors has become a common practice, immune responses related to immunosenescence in those kidney allografts have not been studied yet in humans. We performed a retrospective molecular analysis of the T cell immune response in 43 kidney biopsies from patients with acute T cell-mediated rejection including 25 from recipients engrafted with a kidney from expanded criteria donor and 18 from recipients grafted with optimal kidney allograft. The clinical, transplant and acute T cell-mediated rejection characteristics of both groups were similar at baseline. The expression of RORγt, Il-17 and T-bet mRNA was significantly higher in the elderly than in the optimal group (p = 0.02, p = 0.036, and p = 0.01, respectively). Foxp3 mRNA levels were significantly higher in elderly patients experiencing successful acute T cell-mediated rejection reversal (p = 0.03). The presence of IL-17 mRNA was strongly associated with nonsuccessful reversal in elderly patients (p = 0.008). Patients with mRNA IL17 expression detection and low mRNA Foxp3 expression experienced significantly more treatment failure (87.5%) than patients with no mRNA IL17 expression and/or high mRNA Foxp3 expression (26.7%; p = 0.017). Our study suggests that the Th17 pathway is involved in pathogenesis and prognosis of acute T cell-mediated rejection in recipients of expanded criteria allograft.

The Kidney Donor Profile Index (KDPI) of marginal donors allocated by standardized pretransplant donor biopsy assessment: distribution and association with graft outcomes.

Pretransplant donor biopsy (PTDB)-based marginal donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the highest range (e.g. >80 or >90), whose discard rate approximates 50% in the United States. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score<4 [median KDPI: 87; interquartile range (IQR): 78-94] and 62 with a score=4 [median KDPI: 87; IQR: 76-93]; 102 dual transplants [median KDPI: 93; IQR: 86-96]) and 248 single standard transplant controls (median KDPI: 36; IQR: 18-51). PTDB-based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80-90 and of 37% for kidneys with a KDPI of 91-100. Although 1-year estimated GFRs were significantly lower in recipients of marginal kidneys (-9.3, -17.9 and -18.8 mL/min, for dual transplants, single kidneys with PTDB score<4 and =4, respectively; p<0.001), graft survival (median follow-up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 [95% confidence interval: 0.80-1.79; p=0.38]). In conclusion, PTDB-based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.