The Porcine Remnant Kidney Model of Chronic Renal Insufficiency

Misra, Sanjay; Gordon, Jeffery D.; Fu, Alex A.; Glockner, James F.; Chade, Alejandro; Mandrekar, Jayawant; Lerman, Lilach O.; Mukhopadhyay, Debabrata

doi:10.1016/j.jss.2006.04.001

Cited by 33 publications

(52 citation statements)

References 17 publications

(26 reference statements)

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“…For instance, renal insufficiency is associated with increased oxidative stress, which has been associated with increased levels of VEGF-A and other proteins (45,46,60), raising the possibility that WSS may increase VEGF-A levels to even a greater degree in uremic patients. In the present study, we created renal insufficiency with subtotal renal infarction causing chronic kidney disease prior to the placement of the grafts (37,39). In these animals, there were significantly increased BUN and creatinine prior to graft placement compared with baseline values, and the characteristics of their arteriovenous grafts are consistent with those observed in clinical specimens.…”

Section: Discussionmentioning

confidence: 58%

“…Experiments were performed in 21 castrated juvenile male domestic pigs (40 -50 kg, Larson Products, Sargent, MN) with chronic renal insufficiency induced by subtotal renal infarction (37,39). Twenty-eight days after renal infarction, arteriovenous PTFE grafts were placed from the carotid artery to the ipsilateral jugular vein (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Renal insufficiency was induced by subjecting the pigs to total embolization of the left kidney and partial embolization of the right kidney, as previously described (37,39). Briefly, 6-Fr sheaths were placed in the right femoral artery, and the left renal artery was selected using a 5-Fr tapered angled glide catheter (Boston Scientific, Natick, MA).…”

Section: Methodsmentioning

confidence: 99%

“…The aim of this study was to determine temporal changes in WSS, blood flow, and luminal vessel area (using PC MRA/MRI) and the expression of matrix regulatory proteins [VEGF-A and its receptors, MMP-2, and MMP-9, and their inhibitors (TIMP-1 and TIMP-2)] after PTFE graft placement in a porcine model of early venous stenosis formation. Because hemodialysis grafts are used in patients with advanced renal failure and the regulation of the targeted cytokines may be markedly different in the uremic milieu, we performed these experiments using a porcine model of renal insufficiency (37,39).…”

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confidence: 99%

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Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts

Misra¹,

Fu²,

Puggioni³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Venous injury and subsequent venous stenosis formation are responsible for hemodialysis graft failure. Our hypothesis is that these pathological changes are in part related to changes in wall shear stress (WSS) that results in the activation of matrix regulatory proteins causing subsequent venous stenosis formation. In the present study, we examined the serial changes in WSS, blood flow, and luminal vessel area that occur subsequent to the placement of a hemodialysis graft in a porcine model of chronic renal insufficiency. We then determined the corresponding histological, morphometric, and kinetic changes of several matrix regulatory proteins including VEGF-A, its receptors, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and TIMP-2. WSS was estimated by obtaining blood flow and luminal vessel area by performing phase-contrast MRI with magnetic resonance angiography in 21 animals at 1 day after graft placement and prior to death on day 3 ( n = 7), day 7 ( n = 7), and day 14 ( n = 7). At all time points, the mean WSS at the vein-to-graft anastomosis was significantly higher than that at the control vein ( P < 0.05). WSS had a bimodal distribution with peaks on days 1 and 7 followed by a significant reduction in WSS by day 14 ( P < 0.05 compared with day 7) and a decrease in luminal vessel area compared with control vessels. By day 3, there was a significant increase in VEGF-A and pro-MMP-9 followed by, on day 7, increased pro-MMP-2, active MMP-2, and VEGF receptor (VEGFR)-2 ( P < 0.05) and, by day 14, increased VEGFR-1 and TIMP-1 ( P < 0.05) at the vein-to-graft anastomosis compared with control vessels. Over time, the neointima thickened and was composed primarily of α-smooth muscle actin-positive cells with increased cellular proliferation. Our data suggest that hemodialysis graft placement leads to early increases in WSS, VEGF-A, and pro-MMP-9 followed by subsequent increases in pro-MMP-2, active MMP-2, VEGFR-1, VEGFR-2, and TIMP-1, which may contribute to the development of venous stenosis.

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Section: Discussionmentioning

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts

Misra¹,

Fu²,

Puggioni³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…As in humans, neointimal hyperplasia in the pig develops predominantly at the vein-graft anastomosis; however, the process is more rapid, typically evident within 4-6 weeks (18-23). Misra et al (24)(25)(26) have developed a porcine model of renal insufficiency that provides a more relevant background for evaluating treatment effects and the pathophysiology of AVG and AVF, but use of this model is costly and technically challenging.…”

Section: Animal Models Of Av Accessmentioning

confidence: 99%

Novel Therapies for Hemodialysis Vascular Access Dysfunction

Terry

Dember

2013

Clinical Journal of the American Society of Nephrology

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SummaryHemodialysis vascular access dysfunction is a major source of morbidity for patients with ESRD. Development of effective approaches to prevent and treat vascular access failure requires an understanding of the underlying mechanisms, suitable models for preclinical testing, systems for targeted delivery of interventions to maximize efficacy and minimize toxicity, and rigorous clinical trials that use appropriate outcome measures. This article reviews the substantial progress and ongoing challenges in developing novel treatments for arteriovenous vascular access failure and focuses on localized rather than systemic interventions.

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Alleviating chronic kidney disease progression through modulating the critical genus of gut microbiota in a cisplatin-induced Lanyu pig model

Lee

Wang

et al. 2020

Journal of Food and Drug Analysis

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The Porcine Remnant Kidney Model of Chronic Renal Insufficiency

Cited by 33 publications

References 17 publications

Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts

Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts

Novel Therapies for Hemodialysis Vascular Access Dysfunction

Alleviating chronic kidney disease progression through modulating the critical genus of gut microbiota in a cisplatin-induced Lanyu pig model

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