The management of dialysis access thrombosis during the COVID-19 pandemic.

BACKGROUND: Maintaining patent access is essential for haemodialysis dependent end stage renal failure patients. The COVID-19 pandemic has significantly affected surgical and interventional radiology services worldwide. We aimed to review the impact COVID-19 has caused to the management of acute dialysis access thrombosis. METHODS: We conducted a single centre retrospective review of outcomes of patients with arteriovenous fistula and arteriovenous graft thrombosis between March and May 2020, which coincided with the first peak of the COVID-19 pandemic in London, and a similar period in the previous year, March-May 2019. Outcomes in both cohorts of patients were compared, including attempts at salvage, salvage success, 1-month patency rates after salvage and subsequent surgery on the same access. We also analysed the use of tunnelled haemodialysis lines (THL), either due to failed salvage attempts or when salvage was not attempted. RESULTS: There was a similar incidence of access thrombosis in both periods (26 cases in 2019, 38 in 2020). There were 601 patients dialysing via an arteriovenous fistula or graft in 2019, and 568 patients in 2020. Access salvage, when attempted, had similar success rates and 1-month patency (salvage success 74% vs 80%, p = 0.39; 1-month patency 55% vs 62%, p = 0.69). The proportion of patients where access salvage was not attempted and a THL inserted was significantly higher in 2020 compared to 2019 (32% vs 4%, p = 0.007). There were more patients who subsequently had surgery to salvage or revise the same access in 2019 compared to 2020 (62% vs 13%, p < 0.001). CONCLUSIONS: During the peak of the COVID-19 pandemic, there were fewer attempts at access salvage. This was a conscious decision due to increased pressure on the healthcare system, access to emergency interventional radiology or operative theatres and the perceived risk/benefit ratio of access salvage. The long-term effects of this change in practice remain unknown.

"Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology."

Chronic kidney disease (CKD) related cardiovascular disease (CVD) is characterized by vascular remodelling with well-established structural and functional changes in the vascular wall such as arterial stiffness, matrix deposition, and calcification. These phenotypic changes resemble pathology seen in ageing, and are likely to be mediated by sustained alterations in gene expression, which may be caused by epigenetic changes such as tissue-specific DNA methylation. We aimed to investigate tissue specific changes in DNA methylation that occur in CKD-related CVD. Genome-wide DNA methylation changes were examined in bisulphite converted genomic DNA isolated from the vascular media of CKD and healthy arteries. Methylation-specific PCR was used to validate the array data, and the association between DNA methylation and gene and protein expression was examined. The DNA methylation age was compared to the chronological age in both cases and controls. Three hundred and nineteen differentially methylated regions (DMR) were identified spread across the genome. Pathway analysis revealed that DMRs associated with genes were involved in embryonic and vascular development, and signalling pathways such as TGFß and FGF. Expression of top differentially methylated gene HOXA5 showed a significant negative correlation with DNA methylation. Interestingly, DNA methylation age and chronological age were highly correlated, but there was no evidence of accelerated age-related DNA methylation in the arteries of CKD patients. In conclusion, we demonstrated that differential DNA methylation in the arterial tissue of CKD patients represents a potential mediator of arterial pathology and may be used to uncover novel pathways in the genesis of CKD-associated complications.

Outcomes of Renal Transplant Recipients With SARS-CoV-2 Infection in the Eye of the Storm: A Comparative Study With Waitlisted Patients.

BACKGROUND: Patients with chronic kidney disease stage 5 and those on immunosuppression are particularly vulnerable and are shielded as per public health strategy. We present our experience of coronavirus disease 2019 (COVID-19) transplant patients in one of the most affected parts of the UK with direct comparison to waitlisted patients. METHODS: A single-center prospective study of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive waitlisted and transplant patients was undertaken to compare these groups and assess clinical outcomes. RESULTS: A total of 60 consecutive symptomatic SARS-CoV-2 positive patients were identified with 32 active waitlisted patients and 28 functioning renal transplants. Demographics were similar. The incidence of symptomatic COVID-19 in the waitlisted group was 9.9% compared to 1.9% in renal transplant patients (P < 0.001). Immunosuppression did not influence initial symptomology. Fifteen percent of patients in the waitlisted and 32% in the transplant groups died (P = 0.726). Mortality as proportion of total waitlisted (321 patients) and transplant population (1434 patients) of our centre was 1.5% and 0.6% (P < 0.001), respectively. C-reactive protein (CRP) at 48 h and peak CRP were associated with mortality in both groups while quick sequential organ failure assessment score at 48 h (P = 0.036) was associated with mortality for transplant patients. CONCLUSIONS: Incidence of COVID-19 is higher in the waitlisted population but transplant patients have more severe disease, reflected by higher mortality. CRP at 48 h can be used as a predictive tool. In the absence of effective treatments, the current strategy of shielding is arguably the most important factor in protecting patients while resuming transplantation.

Spatiotemporal Transition in the Role of Synaptic Inhibition to the Tail Beat Rhythm of Developing Larval Zebrafish.

Significant maturation of swimming in zebrafish (Danio rerio) occurs within the first few days of life when fish transition from coiling movements to burst swimming and then to beat-and-glide swimming. This maturation occurs against a backdrop of numerous developmental changes - neurogenesis, a transition from predominantly electrical to chemical-based neurotransmission, and refinement of intrinsic properties. There is evidence that spinal locomotor circuits undergo fundamental changes as the zebrafish transitions from burst to beat-and-glide swimming. Our electrophysiological recordings confirm that the operation of spinal locomotor circuits becomes increasingly reliant on glycinergic neurotransmission for rhythmogenesis governing the rhythm of tail beats. This transition occurred at the same time that we observed a change in rhythmicity of synaptic inhibition to spinal motoneurons (MNs). When we examined whether the transition from weakly to strongly glycinergic dependent rhythmogenesis occurred at a uniform pace across the length of the spinal cord, we found that this transition occurred earlier at caudal segments than at rostral segments of the spinal cord. Furthermore, while this rhythmogenic transition occurred when fish transition from burst swimming to beat-and-glide swimming, these two transitions were not interdependent. These results suggest that there is a developmental transition in the operation of spinal locomotor circuits that is gradually set in place in the spinal cord in a caudo-rostral temporal sequence.

Successful Repair of a Vasculopathic Aneurysmal Brachial Artery in a Patient with Type 1 Neurofibromatosis.

Vasculopathy is a well-recognized abnormality associated with neurofibromatosis type 1(NF1) and may cause stenoses, aneurysms, and arteriovenous malformations. We report a challenging case of a woman with NF1, who presented with spontaneous rupture of a brachial aneurysm around her right elbow, on a background of previous debulking and soft tissue reconstructive surgery in the same arm. She underwent successful delayed reconstruction of the brachial artery using an autologous great saphenous vein graft.

Post-operative arterio-venous fistula blood flow influences primary and secondary patency following access surgery.

PURPOSE: Primary arteriovenous fistula arterio venous fistula (AVF) formation has proven to be the best and optimal vascular access for the majority of haemodialysis patients. At present there are limited data to suggest which haemodynamic parameters most correlate with the likelihood of early failure. The aim of this study is to identify the haemodynamic predictors of early failure, hence identify which fistulae may benefit from timely pre-emptive intervention. MATERIAL AND METHODS: Retrospective analysis of data was performed of 201 patients undergoing native AVF creation over a one year period. Demographic details, co-morbidity, preoperative vessel calibre were collected. Flow was measured by duplex ultrasound post operatively. RESULTS: Preoperative vein calibre (p = 0.01) and fistula flow (p < 0.001) positively affected primary patency. Age, gender, ethnicity, type of fistula, hypertension and preoperative arterial calibre did not influence outcome. Regression analysis showed that the strength of correlation between early postoperative fistula flow and patency decreased progressively with time. Six week flow predicts early, but not late, failure. ROC analysis identified 300 ml/min flow as the best predictor of patency. Fistulae with flow above 300 ml/min were more likely to remain patent over the next 12 months (p < 0.001, HR = 7.4). CONCLUSION: Postoperative fistula flow of less than 300 ml/min identifies AVFs at high risk of early failure. These may be candidates for early intervention with balloon assisted maturation. The findings of this retrospective cohort study strongly support the need for a more robust prospectively designed trial identifying haemodynamic factors that can predict mid and long-term AVF patency.

Do we need a different organ allocation system for kidney transplants using donors after circulatory death?

BACKGROUND: There is no national policy for allocation of kidneys from Donation after circulatory death (DCD) donors in the UK. Allocation is geographical and based on individual/regional centre policies. We have evaluated the short term outcomes of paired kidneys from DCD donors subject to this allocation policy. METHODS: Retrospective analysis of paired renal transplants from DCD's from 2002 to 2010 in London. Cold ischemia time (CIT), recipient risk factors, delayed graft function (DGF), 3 and 12 month creatinine) were compared. RESULTS: Complete data was available on 129 paired kidneys.115 pairs were transplanted in the same centre and 14 pairs transplanted in different centres. There was a significant increase in CIT in kidneys transplanted second when both kidneys were accepted by the same centre (15.5 ± 4.1 vs 20.5 ± 5.8 hrs p<0.0001 and at different centres (15.8 ± 5.3 vs. 25.2 ± 5.5 hrs p=0.0008). DGF rates were increased in the second implant following sequential transplantation (p=0.05). CONCLUSIONS: Paired study sequential transplantation of kidneys from DCD donors results in a significant increase in CIT for the second kidney, with an increased risk of DGF. Sequential transplantation from a DCD donor should be avoided either by the availability of resources to undertake simultaneous procedures or the allocation of kidneys to 2 separate centres.

Acute facial oedema post live-donor renal transplantation.

Facial oedema leading to airway compromise immediately after surgery is a rare event. We report a case of acute facial swelling sufficient to cause a significant obstruction of the patient's airway in recovery. We believe it was caused by partial obstruction of the venous drainage from the head associated with a sudden and large fluid load. A 35-year-old man underwent a live ABO-incompatible renal transplantation during which a central line was inserted into the right subclavian vein and a large volume of fluid was given intraoperatively. He also had a longstanding permacatheter on the left side used for haemodialysis. In the recovery room he developed acute facial swelling which did not resolve with steroids or antihistamines. He was managed by intubation of his airway and ventilation in the intensive care unit overnight before he made a complete recovery with no further intervention. We hypothesise that this event was related to an impaired venous return from his head secondary to the central venous line and the permacatheter partially obstructing the venous drainage from his head and neck combined with an acute large venous fluid load.