Background Although considered the best means of providing haemodialysis, arteriovenous fistulas (AVFs) may increase long-term cardiovascular morbidity and mortality because of the low peripheral resistance and high cardiac output that develops. We assessed whether a randomised controlled trial (RCT) examining the cardiovascular impact of AVF ligation in stable renal transplant patients was feasible. Methods A parallel two-arm, non-blinded, feasibility trial enrolled forty consenting adult kidney recipients with a patent AVF and with good transplant function (estimated Glomerular Filtration Rate > 35 mL/min/1.73m 2 ) from six UK centres. At baseline, each had maximal oxygen consumption (peak VO 2 ) quantified by cardiopulmonary exercise testing (CPET), and activity levels and other quality of life (QoL) domains assessed by wrist accelerometry and Short Form-36 questionnaire responses. Participants were randomised by a web response system in a 1:1 ratio to surgical disconnection of their AVF (intervention) or to continued conservative management (standard care), stratified according to AVF site (wrist or elbow) and AVF volume flow (low or high). The assessments were repeated six months later. The primary outcome measure was the proportion of approached patients who completed the study, with pre-determined red-amber-green criteria determining progression to the main study. Secondary non-blinded clinical outcome measures included: peak VO 2 ; physical functioning (SF-36 score); total activity levels (mg/day); N-terminal pro B-type natriuretic peptide (NT-proBNP – higher values indicating myocardial overstretch). Key findings The target 40 patients were recruited to the trial and randomised. However, only 27 (67.5%) received the allocated intervention and completed both CPETs, with 7 of 20 (35%) randomised to AVF disconnection not undergoing surgery, below the predetermined completion rate required for trial progression. Compliance to wearing the wrist accelerometers was generally much better. With regards secondary outcome measures, neither peak VO 2 (the proposed primary end-point for the main RCT) nor accelerometry activity levels were increased following AVF disconnection. There were, however, apparent improvements in 6-monthly NT-proBNP levels and physical functioning scores. Conclusions Although based on small numbers of participants, AVF ligation may be associated with improvements in physical functioning and NT-proBNP values. However, the much higher rates of participant drop-out than anticipated (particularly for the intervention group) would make successful delivery of the proposed RCT extremely challenging, with impractically large numbers of participants required. Alternative study designs should be considered. Trial registration number ISRCTN49033491. Trial Funding: National Institute for Health Research (NIHR) Research for Patient Benefit Funding grant (NIHR202255).

Donor livers may contain occult fibrin, which is associated with adverse transplant outcomes in livers donated after brain death (DBD) and circulatory death (DCD). Ex situ normothermic machine perfusion (NMP) may allow fibrinolytic therapy before transplantation. Before undertaking a large efficacy study for the prophylaxis of cholangiopathy, we wished to assess the safety of a protocol comprising alteplase and fresh frozen plasma (FFP), the latter as a source of plasminogen, and also to ascertain which of the 4 possible treatment strategies was associated with the greatest fibrin breakdown, as judged by D-dimer release. Eighty livers, 40 DBD and 40 DCD, were randomized to 1 of 5 groups of 16 each, receiving 10 mg or 20 mg alteplase, 1 or 2 units (250 mL) of FFP, with alteplase and FFP being delivered into either the hepatic artery cannula or portal reservoir at the start of NMP. The primary endpoint was bleeding post-transplant. Forty-four of 64 treated livers were transplanted, as were 12 of the 16 control livers receiving FFP alone. There was no increase in post-implant bleeding or blood transfusion requirement of any alteplase-treated liver compared with the FFP alone control group. All 4 alteplase groups were associated with more D-dimer release than the FFP alone control group; 10 mg alteplase was as effective as 20 mg, and delivery into the portal reservoir was as effective as delivery into the hepatic artery cannula. The protocol achieving release of most D-dimers involved 10 mg alteplase being delivered directly into the portal reservoir containing 2 units of FFP. Portal delivery was found to be more straightforward than infusion into the hepatic artery cannula. The combination of alteplase with FFP appeared safe, with no bleeding complications.

BACKGROUND:Normothermic regional perfusion (NRP) has shown superior outcomes in donation after circulatory death, with a low incidence of biliary complications. Not all NRP parameters are unequivocal in supporting transplantation, and further assessment may be required using ex situ normothermic machine perfusion (NMP). Theater and recipient factors may also require extended preservation using NMP. The present study reports our experience with sequential NRP-NMP livers. METHODS:Single-center retrospective analysis of livers undergoing both NRP and NMP, divided into cohorts based on indication for NMP: D-NRP-NMP for donor indications and R-NRP-NMP where the indication was recipient/logistical reason. RESULTS:There were 70 NRP-NMP assessments between May 2017 and August 2024. Sixty-five percent (24/37) of D-NRP-NMP livers and 85% (28/33) of R-NRP-NMP livers were transplanted. Two-thirds of the livers (19/30) failing NRP lactate criteria in the D-NRP-NMP group were transplanted after favorable NMP. Similarly, 60% (9/15) of livers failing NRP alanine transaminase (ALT) cutoff criteria, including 3 livers with ALT >1000 U/L, were successfully transplanted. Collectively, 11 livers (30%) failed both lactate and ALT criteria, with NRP-NMP able to recover 7 (64%) of these livers for transplant. Overall, outcomes of NRP-NMP were satisfactory with 2% primary nonfunction, 23% Olthoff early allograft dysfunction, 56% Kidney Disease Improving Global Outcome acute kidney injury stage ≥2, and 6% nonanastomotic stricture, none requiring biliary intervention. There was no difference in transplant outcomes between the 2 groups, with similar 1- and 3-y patient and graft survival. CONCLUSIONS:NRP and NMP are complementary, with further NMP assessment able to use liver grafts with marginal NRP parameters or facilitating increased preservation time.

Background Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure. Objective To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency. Design A prospective multicentre observational cohort study (the ‘SONAR’ study). Setting Seventeen haemodialysis centres in the UK. Participants Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created. Intervention Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings. Main outcome measures Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months. Results A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas’ non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset ( n = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data. Conclusions Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit. Trial Registration This trial is registered as ISRCTN36033877 and ISRCTN17399438. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment ; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.

Introduction:We assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention.Methods:Consenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling.Results:Of 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9-77.3]; elbow, 66.7% [48.9-84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan's findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data.Conclusion:Early ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation.

IntroductionArteriovenous fistulas (AVFs) are considered the best and safest modality for providing haemodialysis in patients with end-stage renal disease. Only 20% of UK centres achieve the recommended 80% target for achieving dialysis of the prevalent dialysis population via permanent access (as opposed to a central venous catheter). This is partly due to the relatively poor maturation rate of newly created fistulas, with as many as 50% of fistulas failing to mature.The Surveillance Of arterioveNous fistulAe using ultRasound study will examine whether a protocolised programme of Doppler ultrasound (US) surveillance can identify, early after creation, potentially correctable problems in those AVFs that subsequently fail to mature.Methods and analysisThis is a multicentre observational study that will assess newly created AVFs by Doppler US performed at 2, 4, 6 and 10 weeks after creation. The primary outcome measure will be primary fistula patency at week 10. Secondary outcome measures include: successful use of the fistula; clinical suitability for dialysis; creation of new fistula or radiological salvage; fistula thrombosis; secondary fistula patency rate and patient acceptability.Ethics and disseminationThe study has been approved by the Cambridgeshire and Hertfordshire Research Ethics Committee and by the Health Research Authority (REC 18/EE/0234). The results generated from this work will be published as open access, within 3 years of trial commencement. We will also present our findings at key national/international renal meetings, as well as support volunteers at renal patient groups to disseminate the trial outcome.Trial registration numberISRCTN36033877