Failure of hemodialysis access is caused mostly by venous intimal hyperplasia, a fibro-muscular thickening of the vessel wall. The pathogenesis of venous neointimal hyperplasia in primary ...arteriovenous fistulae consists of processes that have been identified as upstream and downstream events. Upstream events are the initial events producing injury of the endothelial layer (surgical trauma, hemodynamic shear stress, vessel wall injury due to needle punctures, etc.). Downstream events are the responses of the vascular wall at the endothelial injury that consist of a cascade of processes including leukocyte adhesion, migration of smooth muscle cells from the media to the intimal layer, and proliferation. In arteriovenous fistulae, the stenoses occur in specific sites, consistently related to the local hemodynamics determined by the vessel geometry and blood flow pattern. Recent findings that the localization of these sites matches areas of disturbed flow may add new insights into the pathogenesis of neointimal hyperplasia in the venous side of vascular access after the creation of the anastomosis. The detailed study of fluid flow motion acting on the vascular wall in anastomosed vessels and in the arm vasculature at the patient-specific level may help to elucidate the role of hemodynamics in vascular remodeling and neointimal hyperplasia formation. These computational approaches may also help in surgical planning for the amelioration of clinical outcome. This review aims to discuss the role of the disturbed flow condition in acting as upstream event in the pathogenesis of venous intimal hyperplasia and in producing subsequent local vascular remodeling in autogenous arteriovenous fistulae used for hemodialysis access. The potential use of blood flow analysis in the management of vascular access is also discussed.
Arteriovenous fistula (AVF) is the first choice for providing vascular access for hemodialysis patients, but maintaining its patency is challenging. AVF failure is primarily due to development of ...neointimal hyperplasia (NH) and subsequent stenosis. Using idealized models of AVF we previously suggested that reciprocating hemodynamic wall shear is implicated in vessel stenosis. The aim of the present study was to investigate local hemodynamics in patient-specific
side
-
to
-
end
AVF. We reconstructed realistic geometrical models of four AVFs from magnetic resonance images acquired in a previous clinical study. High-resolution computational fluid dynamics simulations using patient-specific blood rheology and flow boundary conditions were performed. We then characterized the flow field and categorized disturbed flow areas by means of established hemodynamic wall parameters. In all AVF, either in upper or lower arm location, we consistently observed transitional laminar to turbulent-like flow developing in the juxta-anastomotic vein and damping towards the venous outflow, but not in the proximal artery. High-frequency fluctuations of the velocity vectors in these areas result in eddies that induce similar oscillations of wall shear stress vector. This condition may importantly impair the physiological response of endothelial cells to blood flow and be responsible for NH formation in newly created AVF.
Abstract Actual surgical creation of vascular access has unacceptable failure rates of which stenosis formation is a major cause. We have shown previously in idealized models of side-to-end ...arteriovenous fistula that disturbed flow, a near-wall hemodynamic condition characterized by low and oscillating fluid shear stress, develops in focal points that corresponds closely to the sites of future stenosis. Our present study was aimed at investigating whether disturbed flow occurs in patient-specific fistulae, too. We performed an image-based computational fluid dynamics study within a realistic model of wrist side-to-end anastomosis fistula at six weeks post-surgery, with subject-specific blood rheology and boundary conditions. We then categorized disturbed flow by means of established hemodynamic wall parameters. The numerical analysis revealed laminar flow within the arterial limbs and a complex flow field in the swing segment, featuring turbulent eddies leading to high frequency oscillation of the wall shear stress vectors. Multidirectional disturbed flow developed on the anastomosis floor and on the whole swing segment. Reciprocating disturbed flow zones were found on the distal artery near the floor and on the inner wall of the swing segment. We have found that both multidirectional and reciprocating disturbed flow develop on the inner side of the swing segment in a patient-specific side-to-end fistula used for vascular access after six weeks post-operatively. This has obvious implications for elucidating the hemodynamic forces involved in the initiation of venous wall thickening in vascular access.
Background In 2007, the International Society of Nephrology funded the Kidney Disease Data Center database to house data from sponsored programs aimed at preventing chronic kidney disease and its ...complications in developing nations. This study compares baseline characteristics and burden of illness among participants from centers in China, Mongolia, and Nepal. An important secondary objective is to show the feasibility of screening for chronic kidney disease and its major risk factors in a diverse group of lower income settings. Study Design Cross-sectional screening study. Setting & Participants Participants from Nepal (n = 8,398), China (n = 1,999), and Mongolia (n = 997). Screening was open to the public for participants in China and Nepal; referral from a general practitioner was required for participants in Mongolia. Outcomes Estimated glomerular filtration rate (eGFR), proteinuria, hypertension, diabetes, obesity, cardiovascular risk. Measurement Demographic and clinical data were collected prospectively using a standard format. Blood and urine specimens were provided according to local protocol. Results Of 11,394 participants, decreased eGFR (<60 mL/min/1.73 m2 ) was present in 7.3%-14% of participants across centers; proteinuria (≥1+) on dipstick (2.4%-10%), hypertension (26%-36%), diabetes (3%-8%), and obesity (body mass index ≥30 kg/m2 ; 2%-20%) were all common. Predicted 5-year cardiovascular risk ≥10% ranged from 20%-89%. Numbers needed to screen to detect a new case of eGFR <60 mL/min/1.73 m2 , hypertension, or diabetes were 2.6 (95% CI, 2.5-2.7), 3.4 (95% CI, 3.1-3.7), and 4.7 (95% CI, 3.3-8.0) for Nepal, China, and Mongolia, respectively. Limitations May not be representative of the general population. Conclusions The acceptable diagnostic yield of abnormalities across these 3 diverse settings suggests that trials of targeted screening and intervention are feasible and warranted in such countries.
Preventing Microalbuminuria in Type 2 Diabetes Ruggenenti, Piero; Fassi, Anna; Ilieva, Anelja Parvanova ...
The New England journal of medicine,
11/2004, Letnik:
351, Številka:
19
Journal Article
Recenzirano
Odprti dostop
In a multicenter, double-blind, placebo-controlled, randomized study, subjects with type 2 diabetes mellitus and hypertension but normal urinary albumin levels were treated with an ...angiotensin-converting–enzyme (ACE) inhibitor (trandolapril) and a non-dihydropyridine calcium-channel blocker (verapamil) alone or in combination to investigate whether treatment could forestall the development of microalbuminuria, which heralds diabetic nephropathy. The use of trandolapril alone or with verapamil appeared to be effective, whereas verapamil alone was no better than placebo.
ACE inhibition may prevent or retard the development of microalbuminuria in patients with type 2 diabetes mellitus.
Type 2 diabetes mellitus is a public health concern, and projections of its future effect are alarming. According to the World Health Organization, diabetes affects more than 170 million people worldwide, and this number will rise to 370 million by 2030.
1
About one third of those affected will eventually have progressive deterioration of renal function.
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The first clinical sign of renal dysfunction in patients with diabetes is generally microalbuminuria (a sign of endothelial dysfunction that is not necessarily confined to the kidney),
4
which develops in 2 to 5 percent of patients per year.
5
,
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In type 2 diabetes, unlike type . . .
Activation of mammalian target of rapamycin (mTOR) pathways may contribute to uncontrolled cell proliferation and secondary cyst growth in patients with autosomal dominant polycystic kidney disease ...(ADPKD). To assess the effects of mTOR inhibition on disease progression, we performed a randomized, crossover study (The SIRENA Study) comparing a 6-month treatment with sirolimus or conventional therapy alone on the growth of kidney volume and its compartments in 21 patients with ADPKD and GFR>or=40 ml/min per 1.73 m2. In 10 of the 15 patients who completed the study, aphthous stomatitis complicated sirolimus treatment but was effectively controlled by topical therapy. Compared with pretreatment, posttreatment mean total kidney volume increased less on sirolimus (46+/-81 ml; P=0.047) than on conventional therapy (70+/-72 ml; P=0.002), but we did not detect a difference between the two treatments (P=0.45). Cyst volume was stable on sirolimus and increased by 55+/-75 ml (P=0.013) on conventional therapy, whereas parenchymal volume increased by 26+/-30 ml (P=0.005) on sirolimus and was stable on conventional therapy. Percentage changes in cyst and parenchyma volumes were significantly different between the two treatment periods. Sirolimus had no appreciable effects on intermediate volume and GFR. Albuminuria and proteinuria marginally but significantly increased during sirolimus treatment. In summary, sirolimus halted cyst growth and increased parenchymal volume in patients with ADPKD. Whether these effects translate into improved long-term outcomes requires further investigation.
Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease.
The fluid filling renal cysts in human polycystic kidneys is secreted chiefly by the tubular ...epithelium lining the cysts via secondary chloride transport. Inhibiting this process by somatostatin therapy should induce shrinking of renal cysts.
In this randomized, cross-over, placebo-controlled trial we compared the risk/benefit profile of 6-month treatment with long-acting somatostatin (octreotide-LAR, 40mg intramuscularly every 28 days) or placebo in autosomal-dominant polycystic kidney disease (ADPKD) patients with mild-to-moderate renal insufficiency and no evidence of other kidney disease. Volumes of kidney structures were evaluated by a two-slice computed tomography (CT) scanner; while glomerular filtration rate (GFR) was estimated by iohexol plasma clearance.
One patient on somatostatin and one on placebo were prematurely withdrawn because of nonsymptomatic, reversible colelithiasis and asthenia, respectively. In the remaining 12 patients somatostatin was well tolerated. Kidney volume increased by 71 ± 107mL (P < 0.05) on somatostatin and by 162 ± 114mL (P < 0.01) on placebo. The percent increase was significantly lower on somatostatin (2.2 ± 3.7% vs. 5.9 ± 5.4%) (P < 0.05). Cystic volume tended to increase less on somatostatin than on placebo (3.0 ± 6.5% vs. 5.6 ± 5.8%). The “parenchymal” volume nonsignificantly increased by 2.5 ± 8.4% on placebo and slightly decreased by 4.4 ± 8.9% on somatostatin. The GFR did not change significantly during both treatment periods.
In ADPKD patients, 6-month somatostatin therapy is safe and may slow renal volume expansion. This may reflect an inhibited growth in particular of smallest cysts beyond the detection threshold of CT scan evaluation. Whether this effect may prove renoprotective in the long term should be tested in additional trials of longer duration.
Endothelial cells are constantly exposed to blood flow and the resulting frictional force, the wall shear stress, varies in magnitude and direction with time, depending on vasculature geometry. ...Previous studies have shown that the structure and function of endothelial cells, and ultimately of the vessel wall, are deeply affected by the nature of wall shear stress waveforms. To investigate the in vitro effects of these stimuli, we developed a compact, programmable, real-time operated system based on cone-and-plate geometry, that can be used within a standard cell incubator. To verify the capability to replicate realistic shear stress waveforms, we calculated both analytically and numerically to what extent the system is able to correctly deliver the stimuli defined by the user at plate level. Our results indicate that for radii greater than 25 mm, the shear stress is almost uniform and directly proportional to cone rotation velocity. We further established that using a threshold of 10 Hz of wall shear stress waveform frequency components, oscillating flow conditions can be reproduced on cell monolayer surface. Finally, we verified the capability of the system to perform long-term flow exposure experiments ensuring sterility and cell culture viability on human umbilical vein endothelial cells exposed to unidirectional and oscillating shear stress. In conclusion, the system we developed is a highly dynamic, easy to handle, and able to generate pulsatile and unsteady oscillating wall shear stress waveforms. This system can be used to investigate the effects of realistic stimulations on endothelial cells, similar to those exerted in vivo by blood flow.
Vascular access dysfunction is one of the main causes of morbidity and hospitalization in hemodialysis patients. This major clinical problem points out the need for prediction of hemodynamic changes ...induced by vascular access surgery. Here we reviewed the potential of a patient-specific computational vascular network model that includes vessel wall remodeling to predict blood flow change within 6 weeks after surgery for different arteriovenous fistula configurations. For model validation, we performed a multicenter, prospective clinical study to collect longitudinal data on arm vasculature before and after surgery. Sixty-three patients with newly created arteriovenous fistula were included in the validation data set and divided into four groups based on fistula configuration. Predicted brachial artery blood flow volumes 40 days after surgery had a significantly high correlation with measured values. Deviation of predicted from measured brachial artery blood flow averaged 3% with a root mean squared error of 19.5%, showing that the computational tool reliably predicted patient-specific blood flow increase resulting from vascular access surgery and subsequent vascular adaptation. This innovative approach may help the surgeon to plan the most appropriate fistula configuration to optimize access blood flow for hemodialysis, potentially reducing the incidence of vascular access dysfunctions and the need of patient hospitalization.
Despite recent clinical and technological advancements, the vascular access (VA) for haemodialysis still has significant early failure rates after arteriovenous fistula (AVF) creation. VA failure is ...mainly related to the haemodynamic conditions that trigger the phenomena of vascular wall disease such as intimal hyperplasia (IH) or atherosclerosis.
We performed transient computational fluid dynamics simulations within idealized three-dimensional models of 'end-to-side' and 'end-to-end' radio-cephalic anastomosis, using non-Newtonian blood and previously measured flows and division ratio in subjects requiring primary access procedure as boundary conditions.
The numerical simulations allowed full characterization of blood flow inside the AVF and of patterns of haemodynamic shear stress, known to be the major determinant of vascular remodelling and disease. Wall shear stress was low and oscillating in zones where flow stagnation occurs on the artery floor and on the inner wall of the juxta-anastomotic vein.
Zones of low and oscillatory shear stress were located in the same sites where luminal reduction was documented in previous experimental studies on sites stenosis distribution in AVF. We conclude that even when exposed to high flow rates, there are spot regions along the AVF exposed to athero-prone shear stress that favour vessel stenosis by triggering IH.
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