Renal function, uraemia and early arteriovenous fistula failure

Background Guidance varies regarding the optimal timing of arteriovenous fistula (AVF) creation. The aim of this study was to evaluate the association between uraemia, haemodialysis and early AVF failure. Methods Immunoblotting and cell proliferation assays were performed on vascular smooth muscle cells (VSM) cells isolated from long saphenous vein samples to evaluate the cells’ ability to proliferate when stimulated with uraemic (post-dialysis) and hyperuraemic (pre-dialysis) serum. Clinical data was collected prospectively for 569 consecutive radiocephalic (RCF) and brachiocephalic (BCF) fistulae. The primary outcome was AVF failure at 6 weeks. Dialysis status (haemodialysis (HD); pre-dialysis (Pre-D)), eGFR and serum urea were evaluated to determine if they affected early AVF failure. Results Human VSM cells demonstrated increased capacity to proliferate when stimulated with hyperuraemic serum. There was no significant difference in early failure rate of either RCF or BCF depending on dialysis status (pre-D RCF 31.4% (n = 188); pre-D BCF 22.4% (n = 165); HD RCF 29.3% (n = 99); HD BCF 25.9% (n = 116); p = 0.34). There was no difference in mean eGFR between those patients with early AVF failure and those without (11.2+/-0.2 ml/min/1.73 m2 vs. 11.6+/-0.4 ml/min/1.73 m2; p = 0.47). Uraemia was associated with early AVF failure (serum urea: 35.0+/-0.7 mg/dl vs. 26.6+/-0.3 mg/dl (p &lt; 0.001)). Conclusions We present the first in vivo evidence of an association between adverse early AVF outcomes and uraemia. This is supported mechanistically by in vitro work demonstrating a pro-mitogenic effect of hyperuraemic serum. We hypothesise that uraemia-driven upregulation of VSM cell proliferation at the site of surgical insult in contributes to higher early AVF failure rates.</p

Immediate access arteriovenous grafts versus tunnelled central venous catheters: study protocol for a randomised controlled trial

Background Autologous arteriovenous fistulae (AVF) are the optimal form of vascular access for haemodialysis. AVFs typically require 6 to 8 weeks to “mature” from the time of surgery before they can be cannulated. Patients with end-stage renal disease needing urgent vascular access therefore traditionally require insertion of a tunnelled central venous catheter (TCVC). TCVCs are associated with high infection rates and central venous stenosis. Early cannulation synthetic arteriovenous grafts (ecAVG) provide a novel alternative to TCVCs, permitting rapid access to the bloodstream and immediate needling for haemodialysis. Published rates of infection in small series are low. The aim of this study is to compare whether TCVC ± AVF or ecAVG ± AVF provide a better strategy for managing patients requiring immediate vascular access for haemodialysis. Methods/design This is a prospective randomised controlled trial comparing the strategy of TCVC ± AVF to ecAVG ± AVF. Patients requiring urgent vascular access will receive a study information sheet and written consent will be obtained. Patients will be randomised to receive either: (i) TCVC (and native AVF if this is anatomically possible) or (ii) ecAVG (± AVF). 118 patients will be recruited. The primary outcome is systemic bacteraemia at 6 months. Secondary outcomes include culture-proven bacteraemia rates at 1 year and 2 years; primary and secondary patency rates at 3, 6, 12 and 24 months; stenoses; re-intervention rates; re-admission rate; mortality and quality of life. Additionally, treatment delays, impact on service provision and cost-effectiveness will be evaluated. Discussion This is the first randomised controlled trial comparing TCVC to ecAVG for patients requiring urgent vascular access for haemodialysis. The complications of TCVC are considered an unfortunate necessity in patients requiring urgent haemodialysis who do not have autologous vascular access. If this study demonstrates that ecAVGs provide a safe and practical alternative to TCVC, this could instigate a paradigm shift in nephrology thinking and access planning.</p

Ferumoxytol-enhanced magnetic resonance angiography for the assessment of potential kidney transplant recipients

Objectives: Traditional contrast-enhanced methods for scanning blood vessels using magnetic resonance imaging (MRI) or CT carry potential risks for patients with advanced kidney disease. Ferumoxytol is a superparamagnetic iron oxide nanoparticle preparation that has potential as an MRI contrast agent in assessing the vasculature. Methods: Twenty patients with advanced kidney disease requiring aorto-iliac vascular imaging as part of pre-operative kidney transplant candidacy assessment underwent ferumoxytol-enhanced magnetic resonance angiography (FeMRA) between December 2015 and August 2016. All scans were performed for clinical indications where standard imaging techniques were deemed potentially harmful or inconclusive. Image quality was evaluated for both arterial and venous compartments. Results: First-pass and steady-state FeMRA using incremental doses of up to 4 mg/kg body weight of ferumoxytol as intravenous contrast agent for vascular enhancement was performed. Good arterial and venous enhancements were achieved, and FeMRA was not limited by calcification in assessing the arterial lumen. The scans were diagnostic and all patients completed their studies without adverse events. Conclusions: Our preliminary experience supports the feasibility and utility of FeMRA for vascular imaging in patients with advanced kidney disease due for transplant listing, which has the advantages of obtaining both arteriography and venography using a single test without nephrotoxicity

The case for early use of rapid whole-genome sequencing in management of critically ill infants: late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease, and recurrent infections.

Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease, and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy-number variants, and single gene mutations. CDH is the most expensive noncardiac congenital defect. Management frequently requires implementation of extracorporeal membrane oxygenation (ECMO), which increases management expenditures 2.4-3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in-hospital survival of 80%-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including postcardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections, and developmental delay. Rapid whole-genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_ 3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day

Cephalic arch stenosis: An analysis of outcome by type of first intervention

Background Cephalic arch stenoses (CAS) occur in near 70% of elbow arteriovenous fistulas. Percutaneous transluminal angioplasty (PTA) remains first-line treatment despite documented stent-grafts (SG) efficacy. The study aim is to report long-term outcomes based on initial treatment of CAS. Methods Retrospective review of 12-year data in single tertiary centre. Outcomes included technical success, rupture rate, primary patency (PP), dialysis performance; categorical variables assessed via χ2 or Fisher’s; nonparametric tests used for skewed data. Kaplan–Meier analysis used for PP and cumulative patency. Cox proportional hazard regression model to assess explanatory variables in PP. Results One hundred one brachio- and radiocephalic fistulas with CAS were included. SG as first intervention had higher success than PTA (85% vs 61%, p = 0.003). Rupture occurred in 9/85 (10.6%) PTA vs 0% in SG (p = 0.046). In a subgroup with poor urea reduction rate (URR), both PTA and SG improved dialysis performance post-intervention (p = 0.002). SG demonstrated better PP than PTA (79,73,60% patency at 3, 6, 9 months; versus 71,51,47%; p = 0.195) and cumulative patency (73,61,61% at 1, 2, 3 years; versus 60,34,26%; p &lt; 0.001). Of the variables analyzed, technical success of PTA was the only discriminating factor (coeff.-1.01; RR 35%, p = 0.035). Accesses that underwent secondary stenting performed better than primarily stented CAS (p = 0.01). Conclusions SG superiority is confirmed in CAS, particularly when angioplasty is unsuccessful. While PTA has short-lived benefits, it can improve dialysis performance. Other than higher success rate, primary CAS stenting did not have advantages compared to post-PTA stenting in our study. Other factors related to inflow, outflow, conduit characteristics are presumed to be involved in access longevity

Advanced Kidney Disease Patient Portal:Implementation and Evaluation with Haemodialysis Patients

Patients on haemodialysis face complex care pathways, a high treatment burden and lower quality-of-life. Working with multidisciplinary domain experts, we have conducted several iterative development cycles to design, develop and evaluate a portal for patients on haemodialysis that can help them better understand and navigate their care pathways. A key functionality of the portal is to improve data and information sharing with clinicians, including on key aspects of quality-of-life through Patients Reported Outcome Measures. A case study was conducted with multidisciplinary experts and patients in the NHS Greater Glasgow and Clyde health board (Scotland), using interviews combined with the System Usability Scale (n=26). Patients' feedback and system use observations were used to further refine the system design requirements and functionalities. Key lessons include: a wide preference for tablet-based input vs paper, identification of case-specific accessibility issues and situational impairment, benefits of self-completed digital data collection in overcoming such issues and promoting patient independence and privacy, with considerations for maintaining perceived value and engagement with such systems and when to offer alternatives

Improving arteriovenous fistula patency : transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation

Creation of an autologous arteriovenous fistula (AVF) for vascular access in haemodialysis is the modality of choice. However neointimal hyperplasia and loss of the luminal compartment result in AVF patency rates of ~60% at 12months. The exact cause of neointimal hyperplasia in the AVF is poorly understood. Vascular trauma has long been associated with hyperplasia. With this in mind in our rabbit model of AVF we simulated cannulation autologous to that undertaken in vascular access procedures and observed significant neointimal hyperplasia as a direct consequence of cannulation. The neointimal hyperplasia was completely inhibited by topical transdermal delivery of the non-steroidal anti-inflammatory (NSAID) diclofenac. In addition to the well documented anti-inflammatory properties we have identified novel anti-proliferative mechanisms demonstrating diclofenac increases AMPK-dependent signalling and reduced expression of the cell cycle protein cyclin D1. In summary prophylactic transdermal delivery of diclofenac to the sight of AVF cannulation prevents adverse neointimal hyperplasic remodelling and potentially offers a novel treatment option that may help prolong AVF patency and flow rates

Improving arteriovenous fistula patency : transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation

Creation of an autologous arteriovenous fistula (AVF) for vascular access in haemodialysis is the modality of choice. However neointimal hyperplasia and loss of the luminal compartment result in AVF patency rates of ~60% at 12months. The exact cause of neointimal hyperplasia in the AVF is poorly understood. Vascular trauma has long been associated with hyperplasia. With this in mind in our rabbit model of AVF we simulated cannulation autologous to that undertaken in vascular access procedures and observed significant neointimal hyperplasia as a direct consequence of cannulation. The neointimal hyperplasia was completely inhibited by topical transdermal delivery of the non-steroidal anti-inflammatory (NSAID) diclofenac. In addition to the well documented anti-inflammatory properties we have identified novel anti-proliferative mechanisms demonstrating diclofenac increases AMPK-dependent signalling and reduced expression of the cell cycle protein cyclin D1. In summary prophylactic transdermal delivery of diclofenac to the sight of AVF cannulation prevents adverse neointimal hyperplasic remodelling and potentially offers a novel treatment option that may help prolong AVF patency and flow rates