BACKGROUND:

Deceased donor kidneys are preserved in cold hypoxic conditions. Providing oxygen during preservation might improve post-transplant outcomes, particularly for kidneys subjected to greater degrees of preservation injury. This study aimed to investigate whether supplemental oxygen during hypothermic machine perfusion (HMP) could improve the outcome of kidneys donated after circulatory death.

METHODS:

This randomised, double-blind, paired, phase 3 trial was done in 19 European transplant centres. Kidney pairs from donors aged 50 years or older, donated after circulatory death, were eligible if both kidneys were transplanted into two different recipients. One kidney from each donor was randomly assigned using permuted blocks to oxygenated hypothermic machine perfusion (HMPO2), the other to HMP without oxygenation. Perfusion was maintained from organ retrieval to implantation. The primary outcome was 12-month estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation in pairs of donated kidneys in which both transplanted kidneys were functioning at the end of follow-up. Safety outcomes were reported for all transplanted kidneys. Intention-to-treat analyses were done. This trial is registered with the ISRCTN Registry, ISRCTN32967929, and is now closed.

FINDINGS:

Between March 15, 2015, and April 11, 2017, 197 kidney pairs were randomised with 106 pairs transplanted into eligible recipients. 23 kidney pairs were excluded from the primary analysis because of kidney failure or patient death. Mean eGFR at 12 months was 50·5 mL/min per 1·73 m2 (SD 19·3) in the HMPO2 group versus 46·7 mL/min per 1·73m2 (17·1) in HMP (mean difference 3·7 mL/min per 1·73m2, 95% CI -1·0 to 8·4; p=0·12). Fewer severe complications (Clavien-Dindo grade IIIb or more) were reported in the HMPO2 group (46 of 417, 11%, 95% CI 8% to 14%) than in the HMP group (76 of 474, 16%, 13% to 20%; p=0·032). Graft failure was lower with HMPO2 (three [3%] of 106) compared with HMP (11 [10%] of 106; hazard ratio 0·27, 95% CI 0·07 to 0·95; p=0·028).

INTERPRETATION:

HMPO2 of kidneys donated after circulatory death is safe and reduces post-transplant complications (grade IIIb or more). The 12-month difference in eGFR between the HMPO2 and HMP groups was not significant when both kidneys from the same donor were still functioning 1-year post-transplant, but potential beneficial effects of HMPO2 were suggested by analysis of secondary outcomes.

FUNDING:

European Commission 7th Framework Programme.

The use of machine perfusion (MP) in liver transplantation (LT) is spreading worldwide. However, its efficacy has not been demonstrated, and its proper clinical use has far to go to be widely implemented. The Società Italiana Trapianti d'Organo (SITO) promoted the development of an evidence-based position paper. A 3-step approach has been adopted to develop this position paper. First, SITO appointed a chair and a cochair who then assembled a working group with specific experience of MP in LT. The Guideline Development Group framed the clinical questions into a patient, intervention, control, and outcome (PICO) format, extracted and analyzed the available literature, ranked the quality of the evidence, and prepared and graded the recommendations. Recommendations were then discussed by all the members of the SITO and were voted on via the Delphi method by an institutional review board. Finally, they were evaluated and scored by a panel of external reviewers. All available literature was analyzed, and its quality was ranked. A total of 18 recommendations regarding the use and the efficacy of ex situ hypothermic and normothermic machine perfusion and sequential normothermic regional perfusion and ex situ MP were prepared and graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. A critical and scientific approach is required for the safe implementation of this new technology.

OBJECTIVE:

Patients with chronic kidney disease (CKD) requiring kidney replacement therapy (KRT) in rural communities encounter many barriers in accessing equitable care and have worse outcomes compared with patients in urban areas. This study aims to describe the perspectives of patients and caregivers on access to KRT in rural communities to inform strategies to maximise access to quality care, and thereby reduce disadvantage, inequity and improve health outcomes.

SETTING:

18 studies (n=593 participants) conducted across eight countries (Australia, Canada, the UK, New Zealand, Ghana, the USA, Tanzania and India).

RESULTS:

We identified five themes: uncertainty in navigating healthcare services (with subthemes of struggling to absorb information, without familiarity and exposure to options, grieving former roles and yearning for cultural safety); fearing separation from family and home (anguish of homesickness, unable to fulfil family roles and preserving sense of belonging in community); intense burden of travel and cost (poverty of time, exposure to risks and hazards, and taking a financial toll); making life-changing sacrifices; guilt and worry in receiving care (shame in taking resources from others, harbouring concerns for living donor, and coping and managing in isolation).

CONCLUSION:

Patients with CKD in rural areas face profound and inequitable challenges of displacement, financial burden and separation from family in accessing KRT, which can have severe consequences on their well-being and outcomes. Strategies are needed to improve access and reduce the burden of obtaining appropriate KRT in rural communities.

OBJECTIVE: To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172). BACKGROUND: In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT. METHODS: Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500 mug), followed by a 2.5 mL/h infusion (somatostatin: 250 mug/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis. RESULTS: Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3% and -29.1%, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7% vs -58.8%; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10% vs -45%; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival. CONCLUSIONS: Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.

The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to physicians and healthcare systems worldwide. Evidence about kidney transplant (KTx) recipients is still limited. A systematic literature review was performed. We included 63 articles published from 1 January until 7 July 2020, reporting on 420 adult KTx recipients with confirmed COVID-19. The mean age of patients was 55 ± 15 years. There was a male predominance (67%). The majority (74%) were deceased donor recipients, and 23% were recently transplanted (<1 year). Most patients (88%) had at least one comorbidity, 29% had two, and 18% three. Ninety-three percent of cases were hospitalized. Among them, 30% were admitted to the intensive care unit, 45% developed acute respiratory distress syndrome, and 44% had acute kidney injury with 23% needing renal replacement therapy. From the hospitalized patients a total of 22% died, 59% were discharged, and 19% were still in hospital at the time of publication. Immunosuppression was reduced in 27%, discontinued in 31%, and remained unchanged in 5%. Hydroxychloroquine was administered to 78% of patients, antibiotics to 73%, and antivirals to 30% while 25% received corticosteroid boluses, 28% received anti-interleukin agents, and 8% were given immunoglobulin. The main finding of our analysis was that the incidence of COVID-19 among kidney transplant patients is not particularly high, but when they do get infected, this is related to significant morbidity and mortality.

BACKGROUND:

Abdominal normothermic regional perfusion (aNRP) for donation after circulatory death is an emerging organ preservation technique that might lead to increased organ utilization per donor by facilitating viability testing, improving transplant outcome by early reversal of ischemia, and decreasing the risk of unintentional surgical damage. The aim of the current review is to evaluate the recent literature on the added value of aNRP when compared to local standard perfusion technique.

METHODS:

The Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline for systematic reviews was used, and relevant literature databases were searched. Primary outcomes were organ utilization rate and patient and graft survival after 1 year. Secondary outcomes included delayed graft function, primary nonfunction, serum creatinine, and biliary complications.

RESULTS:

A total of 24 articles were included in this review. The technique is unanimously reported to be feasible and safe, but the available studies are characterized by considerable heterogeneity and bias.

CONCLUSIONS:

Uniform reported outcome measures are needed to draw more definitive conclusions on transplant outcomes and organ utilization. A randomized controlled trial comparing aNRP with standard procurement technique in donation after circulatory death donors would be needed to show the added value of the procedure and determine its place among modern preservation techniques.

BACKGROUND:

The role of machine perfusion (MP) in the evaluation of liver grafts with macrovesicular steatosis (MaS) remains ill-defined as only a limited number of studies has been reported. The objective of the current study was to provide a systematic review to evaluate the role of MP in the setting of MaS livers.

METHODS:

A systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Eligible articles published up to April 2019 were included using the MEDLINE, Scopus, and Google Scholar databases.

RESULTS:

Among the 422 articles screened, only 16 papers met the inclusion criteria. A total of 54 cases of MP use before liver transplantation were included. Sixteen (29.6%) grafts were from donors after circulatory death. In 22 (40.7%) cases, hypothermic machine perfusion was performed. Normothermic machine perfusion was done in the remaining 32 (59.3%) cases. According to the histological results of the donor core biopsy, a MaS value < 30% was observed in 41 (75.9%) cases, whereas 13 (24.1%) patients had moderate-to-severe (≥ 30%) MaS. Following categorization of the pooled population according to the presence of moderate-to-severe (≥ 30%) MaS in the donor graft, no differences were noted in terms of post-transplant death or severe complications following MP. There was no correlation between the proportion of MaS in the donor graft relative to post-transplant peak ALT among patients treated with MP. Among the entire pooled cohort, there was also no correlation between MaS values and ALT peak (R = 0.13; P = 0.42).

CONCLUSIONS:

MP appears to be feasible and safe in MaS livers. Experience to date has been very limited, and the benefit of MP remains not determined. Prospective studies will need to define better the potential effect of "defatting" drugs used during the perfusion process on MaS.

BACKGROUND:

ARS has been adopted in select patients with lung transplant for the past 2 decades in many centers. Outcomes have been reported sporadically. No pooled analysis of retrospective series has been performed.

OBJECTIVE:

This review and pooled analysis sought to demonstrate objective evidence of improved graft function in lung transplant patients undergoing antireflux surgery (ARS).

METHODS:

In accordance with Meta-analyses of Observational Studies in Epidemiology guidelines, a search of PubMed Central, Medline, Google Scholar, and Cochrane Library databases was performed. Articles documenting spirometry data pre- and post-ARS were reviewed and a random-effects model meta-analysis was performed on forced expiratory volume in 1 second (FEV1) values and the rate of change of FEV1.

RESULTS:

Six articles were included in the meta-analysis. Regarding FEV1 before and after ARS, we observed a small increase in FEV1 values in studies reporting raw values (2.02 ± 0.89 L/1 sec vs 2.14 ± 0.77 L/1 sec; n = 154) and % of predicted (77.1% ± 22.1% vs 81.2% ± 26.95%; n = 45), with a small pooled Cohen d effect size of 0.159 (P = .114). When considering the rate of change of FEV1 we observed a significant difference in pre-ARS compared with post-ARS (-2.12 ± 2.76 mL/day vs +0.05 ± 1.19 mL/day; n = 103). There was a pooled effect size of 1.702 (P = .013), a large effect of ARS on the rate of change of FEV1 values.

CONCLUSIONS:

This meta-analysis of retrospective observational studies demonstrates that ARS might benefit patients with declining FEV1, by examining the rate of change of FEV1 during the pre- and postoperative periods.

The global health crisis due to the fast spread of coronavirus disease (COVID-19) has caused major disruption in all aspects of healthcare. Transplantation is one of the most affected sectors, as it relies on a variety of services that have been drastically occupied to treat patients affected by COVID-19. With this report from two transplant centers in Italy, we aim to reflect on resource organization, organ allocation, virus testing and transplant service provision during the course of the pandemic and to provide actionable information highlighting advantages and drawbacks.To what extent can we preserve the noble purpose of transplantation in times of increased danger? Strategies to minimize risk exposure to the transplant population and health- workers include systematic virus screening, protection devices, social distancing and reduction of patients visits to the transplant center. While resources for the transplant activity are inevitably reduced, new dilemmas arise to the transplant community: further optimization of time constraints during organ retrievals and implantation, less organs and blood products donated, limited space in the intensive care unit and the duty to maintain safety and outcomes.