Perfusate Composition and Duration of Ex-Vivo Normothermic Perfusion in Kidney Transplantation: A Systematic Review.

Ex-vivo normothermic perfusion (EVNP) is an emerging strategy in kidney preservation that enables resuscitation and viability assessment under pseudo-physiological conditions prior to transplantation. The optimal perfusate composition and duration, however, remain undefined. A systematic literature search (Embase; Medline; Scopus; and BIOSIS Previews) was conducted. We identified 1,811 unique articles dating from January 1956 to July 2021, from which 24 studies were deemed eligible for qualitative analysis. The perfusate commonly used in clinical practice consisted of leukocyte-depleted, packed red blood cells suspended in Ringer's lactate solution with Mannitol, dexamethasone, heparin, sodium bicarbonate and a specific nutrient solution supplemented with insulin, glucose, multivitamins and vasodilators. There is increasing support in preclinical studies for non-blood cell-based perfusates, including Steen solution, synthetic haem-based oxygen carriers and acellular perfusates with supraphysiological carbogen mixtures that support adequate oxygenation whilst also enabling gradual rewarming. Extended durations of perfusion (up to 24 h) were also feasible in animal models. Direct comparison between studies was not possible due to study heterogeneity. Current evidence demonstrates safety with the aforementioned widely used protocol, however, extracellular base solutions with adequate oxygenation, supplemented with nutrient and metabolic substrates, show promise by providing a suitable environment for prolonged preservation and resuscitation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021231381, identifier PROSPERO 2021 CRD42021231381.

Comparison of kidney transplant outcomes in HLA compatible and incompatible transplantation: A national cohort study.

BACKGROUND: Reports of HLA incompatible (HLAi) kidney transplant outcomes are inconclusive, especially in the context of lower level Donor Specific Antibodies (DSA). METHODS: Multi-centre national cohort study of HLAi kidney transplant recipients matched in 1:2 ratio with HLA compatible (HLAc) kidney transplant recipients. HLAi defined as DSA identified by Luminex. Antibody mediated rejection (AMR) and transplant-survival were analysed using Kaplan-Meier plots. Propensity score (PS) matching was used to compare recipient and transplant survival between groups. RESULTS: We included 61 HLAi and 122 HLAc recipients; mean age 46 years; 60% female. MFIT0 : 3327 (IQR 1352-6458), 23 (38%) were Flow cytometry crossmatch positive (FC-XMPOS ). DSAPOS /FC-XMPOS transplantation carried an increased risk of AMR at 1 year (52%) compared to DSAPOS /FC-XMNEG (27%) and HLAc (0%). Unadjusted death censored graft loss at 3 years was 13% (HLAi) and 8% (HLAc). Three-year patient survival was 95% in HLAc, 84% in DSAPOS /FC-XMNEG and 69% in DSAPOS /FC-XMPOS recipients; 58% of HLAi deaths were infection-related. HLA incompatibility was associated with a decreased 3-year survival in our PS-matched cohort. CONCLUSION: In kidney transplantation, DSA and positive FC-XM carries an increased risk of AMR. Despite inferior transplant and survival outcomes compared to HLAc transplantation, it remains a realistic option for highly sensitized patients facing prolonged waiting times and reduced survival on dialysis.

Viability assessment and utilization of declined donor kidneys with rhabdomyolysis using ex vivo normothermic perfusion without preimplantation biopsy.

The role of ex vivo normothermic perfusion (EVNP) in both organ viability assessment and reconditioning is increasingly being demonstrated. We report the use of this emerging technology to facilitate the transplantation of a pair of donor kidneys with severe acute kidney injury (AKI) secondary to rhabdomyolysis. Donor creatinine was 10.18 mg/dl with protein (30 mg/dl) present in urinalysis. Both kidneys were declined by all other transplantation units and subsequently accepted by our unit. The first kidney was perfused with red cell-based perfusate at 37°C for 75 min, mean renal blood flow was 110 ml/min/100 g and produced 85 ml of urine. Having demonstrated favorable macroscopic appearance and urine output, the kidney was transplanted into a 61-year-old peritoneal dialysis dependent without complication. Given the reassuring information from the first kidney provided by EVNP, the second kidney was not perfused with EVNP and was directly implanted to a 64-year-old patient. The first kidney achieved primary function and the second functioned well after delayed graft function. Recipient eGFR have stabilized at 88.5 and 55.3, respectively (ml/min/1.73 m2 ), at 2 months posttransplant.

Transplantation of kidneys after normothermic perfusion: A single center experience.

BACKGROUND: In order to expand the pool of usable donors from circulatory death (DCD) there is increasing interest in normothermic regional perfusion (NRP) to assess and improve liver viability.1,2 NRP may also improve outcomes in kidney transplantation.We present our single center experience of outcomes in imported kidneys following NRP. METHODS: Data was obtained from a prospectively maintained database between December 2012 and September 2018. Primary endpoints were incidence of delayed graft function (DGF) and estimated glomerular filtration rate (eGFR). RESULTS: Six-hundred and thirty-two decease donor kidneys were transplanted, 229 from DCD donors, 29 of which had NRP. The DGF rate was lower for NRP versus DCD (six of 29, 20.7% vs. 70 of 200, 35.0%) with reduced duration of DGF. Multivariate analysis demonstrated transplant type to be a statistically significant independent predictor of eGFR at 7 and 14 days. Early transplant function in NRP kidneys was comparable to DBD. There were no graft losses within 30 days in the NRP group. One-year graft loss rate was 3.4% for NRP and 6.0% for standard DCD. CONCLUSION: This data suggests NRP is safe, and reduces rates of DGF and improves early renal transplant function.

Long-Term Functional Patency and Cost-Effectiveness of Arteriovenous Fistula Creation under Regional Anesthesia: a Randomized Controlled Trial.

BACKGROUND: Regional anesthesia improves short-term blood flow through arteriovenous fistulas (AVFs). We previously demonstrated that, compared with local anesthesia, regional anesthesia improves primary AVF patency at 3 months. METHODS: To study the effects of regional versus local anesthesia on longer-term AVF patency, we performed an observer-blinded randomized controlled trial at three university hospitals in Glasgow, United Kingdom. We randomly assigned 126 patients undergoing primary radiocephalic or brachiocephalic AVF creation to receive regional anesthesia (brachial plexus block; 0.5% L-bupivacaine and 1.5% lidocaine with epinephrine) or local anesthesia (0.5% L-bupivacaine and 1% lidocaine). This report includes findings on primary, functional, and secondary patency at 12 months; reinterventions; and additional access procedures (primary outcome measures were previously reported). We analyzed data by intention to treat, and also performed cost-effectiveness analyses. RESULTS: At 12 months, we found higher primary patency among patients receiving regional versus local anesthesia (50 of 63 [79%] versus 37 of 63 [59%] patients; odds ratio [OR], 2.7; 95% confidence interval [95% CI], 1.6 to 3.8; P=0.02) as well as higher functional patency (43 of 63 [68%] versus 31 of 63 [49%] patients; OR, 2.1; 95% CI, 1.5 to 2.7; P=0.008). In 12 months, 21 revisional procedures, 53 new AVFs, and 50 temporary dialysis catheters were required. Regional anesthesia resulted in net savings of £195.10 (US$237.36) per patient at 1 year, and an incremental cost-effectiveness ratio of approximately £12,900 (US$15,694.20) per quality-adjusted life years over a 5-year time horizon. Results were robust after extensive sensitivity and scenario analyses. CONCLUSIONS: Compared with local anesthesia, regional anesthesia significantly improved both primary and functional AVF patency at 1 year and is cost-effective. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Local Anaesthesia versus Regional Block for Arteriovenous Fistulae, NCT01706354.

The impact of age on patient tolerance of mycophenolate following kidney transplantation.

BACKGROUND: In Scotland, standard maintenance immunosuppression following kidney transplantation consists of mycophenolate (MPA), tacrolimus and prednisolone irrespective of recipient age. We analyzed the tolerability of this immunosuppression regimen and the association with transplant outcomes. METHODS: A national, multicentre retrospective analysis of patients transplanted in 2015 and 2016, comparing graft function, acute rejection, significant infection rates and immunosuppression dosing between patients aged 18 and 59 years (Group 1) and ≥60 years (Group 2). RESULTS: Of the 490 patients, 26% were aged ≥60 years. Acute rejection (AR) rates at 1 year were 15% and 11% in Groups 1 and 2, respectively. Full-dose MPA was poorly tolerated with 53% in Group 1 and 77% in Group 2 requiring dose reduction or cessation. Female gender and age ≥60 years were independent predictors for MPA dose changes. One year following MPA dose reduction, AR risk was low (5%) in Group 2, however, those remaining on full dose MPA had a 79% increased rate of serious infections. CONCLUSION: The majority of renal transplant recipients aged ≥60 fail to tolerate full-dose MPA. In this group, MPA dose reduction is associated with low rejection rates, but full-dose MPA is associated with high infection rates. We suggest that a tailored approach to immunosuppression in elderly recipients incorporating lower doses of MPA may be appropriate.

Interaction between socioeconomic deprivation and likelihood of pre-emptive transplantation: influence of competing risks and referral characteristics - a retrospective study.

Socioeconomic deprivation (SED) influences likelihood of pre-emptive kidney transplantation (PET), but the mechanisms behind this are unclear. We explored the relationships between SED and patient characteristics at referral, which might explain this discrepancy. A retrospective cohort study was performed. SED was measured by Scottish Index of Multiple Deprivation (SIMD). Logistic regression evaluated predictors of PET. A competing risks survival analysis evaluated the interaction between SED and progression to end-stage kidney disease (ESKD) and death. Of 7765 patients with follow-up of 5.69 ± 6.52 years, 1298 developed ESKD requiring RRT; 113 received PET, 64 of which were from live donors. Patients receiving PET were "less deprived" with higher SIMD (5 ± 7 vs. 4 ± 5; P = 0.003). This appeared independent of overall comorbidity burden. SED was associated with a higher risk of death but not ESKD. Higher SIMD decile was associated with a higher likelihood of PET (OR 1.14, 95% CI 1.06, 1.23); the presence of diabetes and malignancy also reduced PET. SED was associated with reduced likelihood of PET after adjustment for baseline comorbidity, and this was not explained by risk of death or faster progression to ESKD. Education and outreach into transplantation should be augmented in areas with higher deprivation.

Effect of regional versus local anaesthesia on outcome after arteriovenous fistula creation: a randomised controlled trial.

BACKGROUND: Arteriovenous fistulae are the optimum form of vascular access in end-stage renal failure. However, they have a high early failure rate. Regional compared with local anaesthesia results in greater vasodilatation and increases short-term blood flow. This study investigated whether regional compared with local anaesthesia improved medium-term arteriovenous fistula patency. METHODS: This observer-blinded, randomised controlled trial was done at three university hospitals in Glasgow, UK. Adults undergoing primary radiocephalic or brachiocephalic arteriovenous fistula creation were randomly assigned (1:1; in blocks of eight) using a computer-generated allocation system to receive either local anaesthesia (0·5% L-bupivacaine and 1% lidocaine injected subcutaneously) or regional (brachial plexus block [BPB]) anaesthesia (0·5% L-bupivacaine and 1·5% lidocaine with epinephrine). Patients were excluded if they were coagulopathic, had no suitable vessels, or had a previous failed ipsilateral fistula. The primary endpoint was arteriovenous fistula patency at 3 months. We analysed the data on an intention-to-treat basis. This study was registered with ClinicalTrials.gov (NCT01706354) and is complete. FINDINGS: Between Feb 6, 2013, and Dec 4, 2015, 163 patients were assessed for eligibility and 126 patients were randomly assigned to local anaesthesia (n=63) or BPB (n=63). All patients completed follow-up on an intention-to-treat basis. Primary patency at 3 months was higher in the BPB group than the local anaesthesia group (53 [84%] of 63 patients vs 39 [62%] of 63; odds ratio [OR] 3·3 [95% CI 1·4-7·6], p=0·005) and was greater in radiocephalic fistulae (20 [77%] of 26 patients vs 12 [48%] of 25; OR 3·6 [1·4-3·6], p=0·03). There were no significant adverse events related to the procedure. INTERPRETATION: Compared with local anaesthesia, BPB significantly improved 3 month primary patency rates for arteriovenous fistulae. FUNDING: Regional Anaesthesia UK, Darlinda's Charity for Renal Research.

Deleterious effects of phosphate on vascular and endothelial function via disruption to the nitric oxide pathway.

BACKGROUND: Hyperphosphataemia is an independent risk factor for accelerated cardiovascular disease in chronic kidney disease (CKD), although the mechanism for this is poorly understood. We investigated the effects of sustained exposure to a high-phosphate environment on endothelial function in cellular and preclinical models, as well as in human subjects. METHODS: Resistance vessels from rats and humans (± CKD) were incubated in a normal (1.18 mM) or high (2.5 mM) phosphate concentration solution and cells were cultured in normal- (0.5 mM) or high-phosphate (3 mM) concentration media. A single-blind crossover study was performed in healthy volunteers, receiving phosphate supplements or a phosphate binder (lanthanum), and endothelial function measured was by flow-mediated dilatation. RESULTS: Endothelium-dependent vasodilatation was impaired when resistance vessels were exposed to high phosphate; this could be reversed in the presence of a phosphodiesterase-5-inhibitor. Vessels from patients with CKD relaxed normally when incubated in normal-phosphate conditions, suggesting that the detrimental effects of phosphate may be reversible. Exposure to high-phosphate disrupted the whole nitric oxide pathway with reduced nitric oxide and cyclic guanosine monophosphate production and total and phospho endothelial nitric oxide synthase expression. In humans, endothelial function was reduced by chronic phosphate loading independent of serum phosphate, but was associated with higher urinary phosphate excretion and serum fibroblast growth factor 23. CONCLUSIONS: These directly detrimental effects of phosphate, independent of other factors in the uraemic environment, may explain the increased cardiovascular risk associated with phosphate in CKD.

Characterizing the early inflammatory contribution of the donor kidney following reperfusion.

BACKGROUND: Donor kidneys contain a large reservoir of passenger leucocytes that contribute to acute rejection via direct alloantigen presentation and pro-inflammatory cytokine secretion. However, the early contribution of these cells following revascularization has not previously been described. We performed a secondary, high-volume preservation flush following cold storage to characterize the inflammatory contribution of the donor kidney upon reperfusion. METHODS: Porcine kidneys were retrieved using a protocol analogous to current UK clinical practice. Following 2 h of cold static preservation, kidneys underwent a secondary flush with Ringer's solution. The venous effluent was collected and leucocytes phenotyped via flow cytometry. Inflammatory mediators, including cytokines and cell-free DNA, were then assessed to determine the inflammatory contribution of the donor kidney. RESULTS: Upon reperfusion, a significant population of donor-derived CD45 + leucocytes mobilized from the renal vasculature via the renal vein [mean 4.738 × 10 8 (SD 1.348 × 10 8 )]. Within this population, T cells were dominant, representing >60% of the leucocyte repertoire. Granulocytes, monocytes and natural killer cells were also identified, but in comparatively lower numbers. Significant concentrations of cytokines and cell-free DNA were also eluted upon reperfusion. CONCLUSIONS: The donor kidney contains a significant immune load that rapidly mobilizes following reperfusion. Performing a secondary preservation flush prior to implantation may reduce this inflammatory burden via diversion of donor leucocytes and inflammatory mediators from entry into the recipient circulation. This may modulate direct presentation and reduce the inflammatory contribution of the donor kidney following transplantation.

A comparison of the effects of oral vs. intravenous hydration on subclinical acute kidney injury in living kidney donors: a protocol of a randomised controlled trial.

BACKGROUND: Optimal treatment for established renal failure is living donor kidney transplantation. However this pathway exposes healthy individuals to significant reduction in nephron mass via major surgical procedure. Laparoscopic donor nephrectomy is now the most common method for live donor transplantation, reducing both donor post-operative pain and recovery time. However this procedure exposes kidneys to additional haemodynamic stresses. It has been suggested that donor hydration-particularly the use of preoperative intravenous fluids-may counteract these stresses, reducing subclinical acute kidney injury and ultimately improving long-term renal function. This may be important in both preservation of donor renal function and recipient graft longevity. METHODS/DESIGN: A prospective single-centre single-blinded randomized controlled trial will be carried out to determine the effects of donor preoperative intravenous fluids. The primary outcome is donor subclinical acute kidney injury (defined as plasma NGAL, >153 ng/ml) on day 1 postoperatively. Secondary outcomes include intraoperative haemodynamics, recipient subclinical acute kidney injury, perioperative complications and donor sleep quality. Donors will be randomised into two groups: the intervention group will receive active pre-hydration consisting of three litres of intravenous Hartmann's solution between midnight and 8 am before morning kidney donation, while the control group will not receive this. Both groups will receive unlimited oral fluids until midnight, as is routine. Plasma NGAL will be measured at pre-specified perioperative time points, intraoperative haemodynamic data will be collected using non-invasive cardiac output monitoring and clinical notes will be used to obtain demographic and clinical data. The researcher will be blinded to the donor fluid hydration status. Blinded statistical analysis will be performed on an intention-to-treat basis. A prospective power calculation estimates a required sample size of 86 patients. DISCUSSION: This study will provide important data, as there is currently little evidence about the use of donor preoperative fluids in laparoscopic nephrectomy. It is hoped that the results obtained will guide future clinical practice. TRIAL REGISTRATION: This study has been approved by the West of Scotland Research Ethics Committee 3 (reference no. 14/WS/1160, 27 January 2015) and is registered with the International Standard Randomised Controlled Trial Number Register (reference no. ISRCTN10199225 , 20 April 2015).

Risk factors and outcome of stroke in renal transplant recipients.

Stroke incidence is high in end-stage renal disease, and risk factors differ between the dialysis and general populations. However, risk factors and outcomes following renal transplantation remain unclear. We analyzed all adult patients with a functioning renal transplant from 01/01/2007 to 12/31/2012. Data were extracted from the electronic patient record. Variables associated with stroke were identified by survival analyses; demographic, clinical, and imaging and laboratory variables were assessed and case fatality determined. Follow-up was until 05/12/2013. A total of 956 patients were identified (median age 40.1 years, 59.9% male). Atrial fibrillation (AF) prevalence was 9.2%, and 38.2% received a transplant during follow-up. A total of 26 (2.7%) experienced a stroke during 4409 patient-years of follow-up (84.6% ischemic). Stroke incidence was 5.96/1000 patient-years. Factors associated with stroke on regression analysis were prior stroke, diabetes, age, systolic hypertension, and hemoglobin. Atrial fibrillation was associated with time to stroke (P<0.001). Warfarin did not associate with ischemic stroke risk in those with AF. Fatality was 19.2% at 7, 23.1% at 28, and 42.3% at 365 days after stroke. Patients with a functioning renal transplant have a high stroke incidence and case fatality. Unlike those on hemodialysis, risk factors are similar to the general population. We did not demonstrate benefit from warfarin use in those with AF.

Expanded criteria donor and donation after circulatory death renal allografts in the West of Scotland: Their place in the kidney allocation process.

INTRODUCTION: Due to the rising disparity between demand and availability, organs from expanded criteria donors (ECD) and donors after determination of circulatory death (DCD) are increasingly used. The purpose of this study was to report outcomes in recipients of ECD and DCD renal allografts from a single centre. METHODS: A retrospective analysis from a single centre for all renal transplants performed between 2001 and 2010 inclusive was undertaken. SCD (standard criteria donor) and ECD organs were compared, as were DCD and DBD (donation after determination of brain stem death) organs. Baseline data and predefined standard transplant outcomes were collected and compared using appropriate statistical tests. P < 0.05 was defined as significant. RESULTS: 729 renal transplants were performed. Comparing ECD to SCD organs, there was a significant difference in graft survival between groups (logrank for trend, p = 0.032) with ECD organs doing worse than SCD organs. Short-term outcomes showed a similar disparity with a higher 1-year post-transplant creatinine and delayed graft function (DGF) rate in ECD grafts. Nevertheless, outcomes were still clinically acceptable. When comparing DCD to DBD organs, no such differences were apparent, with DCD organs appearing to perform at least as well as DBD organs. In our cohort, unlike some previous studies, DGF rates were similar in both DCD and DBD groups. CONCLUSIONS: Although ECD organs perform less well than SCD organs, outcomes are still acceptable and our results support their continuing use. When considering DCD organs, our data support the view that they should no longer be necessarily regarded as marginal grafts. Our low DGF rates are perhaps explained by local factors contributing to a short CIT.

A novel rodent model of severe renal ischemia reperfusion injury.

Renal ischemia reperfusion injury (IRI) is a major problem, currently without treatments in clinical use. This reflects the failure of animal models to mimic the severity of IRI observed in clinical practice. Most described models lack both the ability to inflict a permanent reduction in renal function and the sensitivity to demonstrate the protective efficacy of different therapies in vivo. To test novel cell-based therapies, we have developed a model of renal IRI in Fisher 344 rats. Animals were subjected to 120 min of unilateral warm ischemia, during which they underwent an intra-renal artery infusion of therapeutic agents or vehicle. At either 2 or 6 weeks post-surgery, animals underwent terminal glomerular filtration rate (GFR) studies by inulin clearance to most accurately quantify renal function. Harvested kidneys underwent histological analysis. Compared to sham operations, saline treated animals suffered a long-term reduction in GFR of ≈50%. Histology revealed short- and long-term disruption of renal architecture. Despite the injury severity, post-operative animal losses are <5%. This model produces a severe, consistent renal injury that closely replicates the pathological processes encountered in clinical medicine. Renal artery infusion mimics the route likely employed in clinical transplantation, where the renal artery is accessible. Inulin clearance characterizes GFR, allowing full assessment of therapeutic intervention. This model is useful for screening therapeutic agents prior to testing in a transplant model. This reduces animal numbers needed to test drugs for clinical transplantation and allows for refinement of dosing schedules.

Predictors of sustained arteriovenous access use for haemodialysis.

BACKGROUND: Guidelines encourage early arteriovenous (AV) fistula (AVF) planning for haemodialysis (HD). The aim of this study was to estimate the likelihood of sustained AV access use taking into account age, sex, comorbidity, anatomical site of first AVF and, for pre-dialysis patients, eGFR and proteinuria. METHODS: 1,092 patients attending our centre who had AVF as their first AV access procedure between January 1, 2000 and August 23, 2012 were identified from the electronic patient record. The primary end-point was time to first sustained AV access use, defined as use of any AV access for a minimum of 30 consecutive HD sessions. RESULTS: 52.9% (n = 578) of the patients ultimately achieved sustained AV access use. The main reasons for AV access non-use were AVF failure to mature and death. The 3-year Kaplan-Meier probability of sustained AV access use was 68.8% for those not on renal replacement therapy (RRT) (n = 688) and 74.2% for those already on RRT (n = 404) at the time of first AVF. By multivariate analysis in patients not on RRT, male sex (HR 2.22; p < 0.001), uPCR (HR 1.03; p = 0.03) and eGFR (hazard ratio, HR 0.85; p < 0.001) were independent predictors of AV access use. In patients already on RRT, age (HR 0.98; p < 0.001) and peripheral vascular disease (HR 0.48; p = 0.02) were independent predictors of AV access use. CONCLUSION: Our data suggest that refinement of the current guideline for timing of AV access creation in planning RRT is justified to take into account individual factors that contribute to the likelihood of technical success and clinical need.

Developing an Injury-Free 15 Hour Preservation Protocol of Donor Porcine Kidneys Using Normothermic Machine Perfusion.

Normothermic machine perfusion (NMP) offers a superior alternative to hypothermic preservation but is currently time limited. Extending this time could electivise transplantation and enable physiologic assessments of functionality. Porcine kidneys were retrieved, stored on ice for 3.5 hours before being placed onto a NMP circuit for 12 hours. Hemodynamics, biochemistry, and urine output were assessed. After 12 hours, kidneys were scored using the clinical assessment score. Biopsies were collected for histological assessment. Kidneys demonstrated continual improvements in hemodynamics. Perfusate sodium concentrations remained within physiologic parameters. Sodium bicarbonate increased over-time with corresponding decreases in lactate, demonstrating active renal gluconeogenesis and Cori cycle processes. Urine production began immediately and was sustained, indicating renal functionality. Under the clinical perfusion assessment score, all kidneys received a score of 1 and would be considered suitable for transplantation. Histological assessment revealed kidneys were injury free. Our NMP protocol safely preserves kidneys for over 15 hours. Successful perfusion was achieved with stable hemodynamics and biochemistry, with maintained urination. Importantly, kidneys remained in optimal health, with no evidence of injury. This may enable electivisation of transplantation, while reducing hypothermic injury.

Pain resulting from arteriovenous fistulae: prevalence and impact.

INTRODUCTION: The burden of pain from cannulation of arteriovenous fistulae (AVF) and the impact it has on quality of life is poorly described in the literature. METHODOLOGY: A pain score questionnaire was employed for all patients in the West of Scotland dialyzing via AVF (n = 461). Pain was assessed using visual analogue score (VAS) and McGill pain score. Patients with severe pain (VAS > 5) were compared to those with minimal pain. RESULTS: The questionnaire as completed by 97.5% of the patients. Median VAS on cannulation was 3 (IQR 0.5 - 4.5). Of those who had completed the questionnaire, 24.4% had severe pain on cannulation and 3.2% experienced severe chronic pain. 53 patients (11.3%) cut a dialysis session short due to pain. Of the patients with severe chronic pain, 46.7% had a physical complication affecting their AVF (e.g., venous stenosis, pseudoaneurysm). Following treatment of the problem, pain improved in 71.4% and resolved completely in 14.3%. Brachiobasilic AVF was associated with a higher incidence of severe pain than either brachiocephalic or radiocephalic AVF (50%, 23.3% and 24.4% respectively; p = 0.03). There was a trend towards more severe pain with rope-ladder cannulation (27.7%) compared to button-hole cannulation (18.2%); however, this difference did not reach statistical significance (p = 0.09). CONCLUSIONS: Pain from AVF is poorly recognized and an under-reported problem. While severe pain resulting in the avoidance of dialysis is rare, it can lead to significant difficulties and ultimate abandonment of AVF. Pain is often suggestive of an underlying anatomical problem.

Health economics aspects of kidney transplantation in Sicily: a benchmark analysis on activity and estimated savings.

Background: International and national registries consistently report substantial differences in kidney transplant (KT) activity despite demonstrable clinical and financial benefits. The study aims to estimate the financial resources gained by KT and produce a benchmark analysis that would inform adequate strategies for the growth of the service. Methods: We analyzed the KT activity in our region between 2017 and 2019. The benchmark analysis was conducted with programs identified from national and international registries. The estimate of financial resources was obtained by applying the kidney transplant coefficient of value; subsequently, we compared the different activity levels and savings generated by the three KT programs. Findings: The KT activity in the region progressively declined in the study years, producing a parallel reduction of the estimated savings. Such savings were substantially inferior when compared to those generated by benchmark programs (range €18-22 million less). Interpretation: The factors influencing the reduced KT activity in the study period with the related "foregone savings" are multiple, as well as interdependent. Organ donation, access to the transplant waiting list, and KT from living donors appear to be the most prominent determinants of the observed different levels of activities. International experience suggests that a comprehensive strategy in the form of a "task force" may successfully address the critical areas of the service reversing the observed trend. The financial impact of a progressively reduced KT activity may be as critical as its clinical implications, jeopardizing the actual sustainability of services for patients with end-stage kidney disease.

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.