Richard Corbett

The effect of in-plane arterial curvature on blood flow and oxygen transport in arterio-venous fistulae

Arterio-Venous Fistulae (AVF) are the preferred method of vascular access for patients with end stage renal disease who need hemodialysis. In this study, simulations of blood flow and oxygen transport were undertaken in various idealized AVF configurations. The objective of the study was to understand how arterial curvature affects blood flow and oxygen transport patterns within AVF, with a focus on how curvature alters metrics known to correlate with vascular pathology such as Intimal Hyperplasia (IH). If one subscribes to the hypothesis that unsteady flow causes IH within AVF, then the results suggest that in order to avoid IH, AVF should be formed via a vein graft onto the outer-curvature of a curved artery. However, if one subscribes to the hypothesis that low wall shear stress and/or low lumen-to-wall oxygen flux (leading to wall hypoxia) cause IH within AVF, then the results suggest that in order to avoid IH, AVF should be formed via a vein graft onto a straight artery, or the inner-curvature of a curved artery. We note that the recommendations are incompatible-highlighting the importance of ascertaining the exact mechanisms underlying development of IH in AVF. Nonetheless, the results clearly illustrate the important role played by arterial curvature in determining AVF hemodynamics, which to our knowledge has been overlooked in all previous studies.

MICROBUBBLE VOID IMAGING: A NON-INVASIVE TECHNIQUE FOR FLOW VISUALISATION AND QUANTIFICATION OF MIXING IN LARGE VESSELS USING PLANE WAVE ULTRASOUND AND CONTROLLED MICROBUBBLE CONTRAST AGENT DESTRUCTION

There is increasing recognition of the influence of the flow field on the physiology of blood vessels and their development of pathology. Preliminary work is reported on a novel non-invasive technique, microbubble void imaging, which is based on ultrasound and controlled destruction of microbubble contrast agents, permitting flow visualisation and quantification of flow-induced mixing in large vessels. The generation of microbubble voids can be controlled both spatially and temporally using ultrasound parameters within the safety limits. Three different model vessel geometries-straight, planar-curved and helical-with known effects on the flow field and mixing were chosen to evaluate the technique. A high-frame-rate ultrasound system with plane wave transmission was used to acquire the contrast-enhanced ultrasound images, and an entropy measure was calculated to quantify mixing. The experimental results were cross-compared between the different geometries and with computational fluid dynamics. The results indicated that the technique is able to quantify the degree of mixing within the different configurations, with a helical geometry generating the greatest mixing, and a straight geometry, the lowest. There is a high level of concordance between the computational fluid dynamics and experimental results. The technique could also serve as a flow visualisation tool.

The Effect of Arterial Curvature on Blood Flow in Arterio-Venous Fistulae: Realistic Geometries and Pulsatile Flow

Arterio-Venous Fistulae (AVF) are regarded as the “gold standard” method of vascular access for patients with End-Stage Renal Disease (ESRD) who require haemodialysis. However, up to 60% of AVF do not mature, and hence fail, as a result of Intimal Hyperplasia (IH). Unphysiological flow and oxygen transport patterns, associated with the unnatural and often complex geometries of AVF, are believed to be implicated in the development of IH. Previous studies have investigated the effect of arterial curvature on blood flow in AVF using idealized planar AVF configurations and non-pulsatile inflow conditions. The present study takes an important step forwards by extending this work to more realistic non-planar brachiocephalic AVF configurations with pulsatile inflow conditions. Results show that forming an AVF by connecting a vein onto the outer curvature of an arterial bend does not, necessarily, suppress unsteady flow in the artery. This finding is converse to results from a previous more idealized study. However, results also show that forming an AVF by connecting a vein onto the inner curvature of an arterial bend can suppress exposure to regions of low wall shear stress and hypoxia in the artery. This finding is in agreement with results from a previous more idealized study. Finally, results show that forming an AVF by connecting a vein onto the inner curvature of an arterial bend can significantly reduce exposure to high WSS in the vein. The results are important, as they demonstrate that in realistic scenarios arterial curvature can be leveraged to reduce exposure to excessively low/high levels of WSS and regions of hypoxia in AVF. This may in turn reduce rates of IH and hence AVF failure.

Suppressing unsteady flow in arterio-venous fistulae

Arterio-Venous Fistulae (AVF) are regarded as the “gold standard” method of vascular access for patients with end-stage renal disease who require haemodialysis. However, a large proportion of AVF do not mature, and hence fail, as a result of various pathologies such as Intimal Hyperplasia (IH). Unphysiological flow patterns, including high-frequency flow unsteadiness, associated with the unnatural and often complex geometries of AVF are believed to be implicated in the development of IH. In the present study, we employ a Mesh Adaptive Direct Search optimisation framework, computational fluid dynamics simulations, and a new cost function to design a novel non-planar AVF configuration that can suppress high-frequency unsteady flow. A prototype device for holding an AVF in the optimal configuration is then fabricated, and proof-of-concept is demonstrated in a porcine model. Results constitute the first use of numerical optimisation to design a device for suppressing potentially pathological high-frequency fl...

Optical Measurement of Anastomotic Oxygenation Dynamics

Oxygen supply is an important predictor of the integrity and viability of luminal structures after surgery. Multispectral imaging is used to study haemodynamics during small bowel anastomosis and arterio-venous fistula formation surgery.

Fibrillary inclusions in light chain proximal tubulopathy associated with myeloma

A 66-year-old retired librarian was referred to the nephrology clinic for evaluation of a recent onset of asymptomatic proteinuria identified at a routine hypertension check-up. She had a 15-year history of hypertension and was treated with ramipril and bendrofluomethazide with no history of diabetes. The urinary protein–creatinine ratio was elevated at 819 mg/mmol, with no evidence of glycosuria, hypoalbuminaemia, acidaemia or impaired renal function (serum creatinine 78 μmol/L). Serum electrophoresis identified a monoclonal IgG kappa band quantified at 20 g/L with associated immunoparesis. Urinary immunofixation demonstrated kappa free light chains. On renal biopsy (Figure 1), there was marked vacuolation of tubular epithelial cells and electron microscopy demonstrated filaments 6 nm in diameter in these cells (Figures 2 and ​and3).3). Congo red staining for amyloid was negative. Immunoflorescence for light chains was negative on frozen sections but protease-digested paraffin sections showed kappa but not lambda light chain deposition in tubular epithelial cells. These findings are consistent with a proximal tubulopathy with fibrillary inclusions related to a kappa light chain plasma cell dyscrasia. Fig. 1. Light microscopy demonstrating vacuolation of tubular epithelial cells. Fig. 2. Electron micrograph of a tubular epithelial cell showing numerous vacuoles in the cytoplasm. Fig. 3. Higher power view of cytoplasmic vacuole showing numerous closely packed filaments 6 nm in diameter. Subsequent bone marrow was hypercellular with 61% plasma cells, which were kappa light chain restricted; she was started on a CTD (cyclophosphamide, thalidomide and dexamethasone) chemotherapeutic regime and has preserved her renal function but has continuing proteinuria. Light chain proximal tubulopathy is an increasingly recognized though still uncommon renal complication of myeloma almost exclusively related to light chain kappa [1]. Some individuals may manifest an associated Fanconi syndrome that was not seen in this woman. Diagnosis can be difficult with frequently non-specific light microscopy findings; on ultrastructural examination, crystalloid inclusions are frequently seen but occasionally may be fibrillary in nature [2]. Crystalloid deposition is thought to occur due to a resistance of the light chain-variable region to lysosymal proteolysis in the proximal tubule [3]. The unusual fibrillary appearances seen here may relate to the physicochemical properties determined by the amino acid sequence in the variable region.

Intensity modulated radiation therapy allows prostate and dose-escalated pelvic radical radiation therapy after renal transplantation

Collateral dose to neighboring tissues limits the deliverable dose of radiation therapy (RT) to the target. Native kidneys receive a minimal dose during standard pelvic lymph node (PLN) RT, because the superior field border is at the L4/5 vertebra for inclusion of internal/external iliac nodes and at the aortic bifurcation for common iliac nodes, both of which are infrarenal. However, a pelvic transplanted kidney may be considered a relative contraindication to radical (curative) pelvic RT. The incidence of radiation-associated renal injury is likely to be underreported because of its long latency, the nonspecific symptoms of renal impairment, and the multifactorial confounding risks. Current dose constraints are based on data from the 1980s to 1990s.1-3 For a native kidney, the risk of late radiation toxicity increases with volume of treated kidney and radiation dose. Recommendations are that one-third or less of the kidney should receive ≥ 50 Gy, whereas two-thirds or less should receive 30 Gy and the whole kidney no more than 23 Gy. A median dose b 17.5Gy is recommended to reduce the risk of

Use of an Uncensored Primary Outcome in a Catheter Design Trial

To the Editor: We read with great interest the article by Van Der Meersch et al. The authors compared Palindrome (Covidien) and HemoStar (Bard) hemodialysis catheters, observing no differences in mean primary assisted patency and catheter-related infections. Removal rates for infection or thrombosis were similar, but thrombolytic use was significantly lower for Palindrome catheters because a significantly higher number of patients using these catheters never required thrombolysis. In our Renal Program, we evaluated outcomes following placement of 61 Palindrome and 58 HemoStar catheters in incident and prevalent dialysis patients. Palindrome catheters are more expensive than HemoStar catheters, and tissue plasminogen activator (tPA), our thrombolytic agent, is a major driver of drug cost in our unit. As part of a quality assurance initiative, we aimed to determine whether exclusive use of Palindrome catheters would reduce cost by limiting tPA use. Baseline characteristics of the 2 groups were similar because there were no criteria used to select which catheter was placed. The incidence rates of tPA use were 4.5 and 4.1 mg/cathetermonth for the Palindrome and HemoStar groups, respectively (incidence rate ratio, 1.07; 95% confidence interval, 0.98-1.18; P5 0.1). Median primary catheter patency was 96 days in the Palindrome group and 132 days in the HemoStar group, with similar time to first tPA use (P5 0.5). Twenty percent of Palindrome and 12% of HemoStar catheters were removed for thrombosis, whereas 11% and 19%, respectively, were removed for infections. In regard to catheter survival and removal for thrombosis or infection, our results agree with those of Van Der Meersch et al. However, our study showed no difference in thrombolytic use. Based on these results, we are still primarily using the HemoStar catheter in our center.

Alternatives to arteriovenous fistulas

In their review, Siddiky and colleagues suggest that arteriovenous fistulas for haemodialysis “offer the best short, intermediate and long term options for renal replacement therapy.”1 Although they have many advantages, one of the few rigorous systematic reviews in vascular access emphasises the often overlooked complication of primary non-function (the fistula never works).2 This occurs …

Conventional dialysis in the elderly: How lenient should our guidelines be?

There has been a dramatic, worldwide expansion in life expectancy across the last century. This has resulted in a progressively more elderly and comorbid population. It is increasingly recognized that healthcare in this group needs to move to the concept of “adding life to years”. Recognition and assessment of frailty is vital in changing our approach in elderly patients. Current guidelines in dialysis have a limited evidence base across all age groups, but particularly the elderly and serve them poorly. Moreover, the burden of guidelines for each comorbidity of the multimorbid patient is increasing and can be conflicting. Finally, there is increasing evidence relating to the harm associated with the delivery of conventional dialysis. In dialysis patients, frailty is the overwhelming determinant in relation to patient‐specific outcomes rather than modality of treatment; therefore, the focus should be on promoting quality of life. We need to focus on new priorities of care when we design guidelines “for people not diseases”. Patient‐centered goal‐directed therapy, arising from shared decision making between physician and patient, should allow adaption of the dialysis regime to maximize opportunities while minimizing treatment‐related morbidity and concentrating on alleviating symptoms.