Early atherosclerosis aggravates the effect of renal artery stenosis on the swine kidney

Urbieta-Caceres, Victor H.; Lavi, Ron; Zhu, Xiang Yang; Crane, John A.; Textor, Stephen C.; Lerman, Amir; Lerman, Lilach O.

doi:10.1152/ajprenal.00159.2010

Cited by 31 publications

(33 citation statements)

References 24 publications

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“…The MDCT study was performed 2 days after MRI to evaluate renal structure and function. MDCT allows accurate and noninvasive evaluation of single-kidney volume, vascular volume fraction, regional perfusion, renal blood flow (RBF), GFR, and tubular function, as we have shown previously (14,38). Briefly, catheters were placed under fluoroscopic guidance in the aorta and right atrium, and flow studies were initiated under baseline conditions.…”

Section: In Vivo Studiesmentioning

confidence: 99%

“…Staining was performed in 5 m of either frozen or paraffin-preserved midhilar renal cross sections following standard protocols, then semiautomatically quantified by a computer-aided image-analysis program (MetaMorph, Meta Imaging, Molecular Devices, Sunnyvale, CA) (38). DHE staining was quantified in 10 random fields, expressed as the fraction of surface area, and the results from all fields were averaged.…”

Section: In Vitro Studiesmentioning

confidence: 99%

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Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation

Woollard

Wang

et al. 2011

American Journal of Physiology-Renal Physiology

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Metabolic syndrome (MetS) is associated with glomerular hyperfiltration and is a risk factor for chronic kidney disease, but the underlying mechanisms are poorly defined. This study tested the hypothesis that increased glomerular filtration rate (GFR) in early MetS is associated with renal adiposity and microvascular proliferation. Twelve MetS-prone Ossabaw pigs were randomized to 10 wk of a standard (lean, n = 6) or atherogenic (MetS, n = 6) diet. Kidney hemodynamics and function, perirenal fat volume, and tubular dynamics were assessed in vivo by multidetector computed tomography (CT) and blood oxygen level-dependent (BOLD)-MRI. Microvascular architecture was assessed ex vivo with micro-CT. Candidate injury mechanisms were evaluated in kidney tissue by Western blotting and histology. Basal GFR, renal blood flow, and renal cortical perfusion and volume were elevated in the MetS group. Perirenal and kidney tissue fat, proximal-nephron intratubular fluid concentration, and endothelial nitric oxide synthase expression were increased in MetS. GFR levels correlated with tissue triglyceride levels. Elevated spatial density of 20- to 40-μm cortical microvessels was accompanied by mild oxidative stress, inflammation, and with proximal tubular vacuolization. Medullary size and perfusion were relatively preserved, and BOLD-MRI showed intact medullary tubular response to furosemide. Increased GFR in early MetS is associated with renal adiposity and microvascular proliferation, which involve mainly the renal cortex and precede significant activation of oxidative stress and inflammation. Renal adiposity and proliferative microvessels may represent novel therapeutic targets for preserving renal function in early MetS.

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Section: In Vivo Studiesmentioning

confidence: 99%

Section: In Vitro Studiesmentioning

confidence: 99%

Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation

Woollard

Wang

et al. 2011

American Journal of Physiology-Renal Physiology

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“…Therefore this experiment stresses the importance of the atherosclerotic environment in inducing renal changes, besides renal artery stenosis. Moreover, additional experimental and clinical data [31][32][33][34] supports the hypothesis that there is no correlation between the patency of the lumen of renal arteries and the degree of renal failure in subjects with ARAS. Also the percentage of patients with improved renal function after revascularization varies significantly when the patients with ostial stenosis are compared with the patients with pure renal stenosis.…”

Section: Mismatch Between Goldblatt Experiments and Clinical Practicementioning

confidence: 54%

When stenting in renal artery stenosis? Update on pathophysiology of ischemic nephropathy and management strategies

Zuccalà¹,

Rapanà²,

Mandreoli³

2013

Ital J Med

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In recent years, decisions taken on the optimal management of patients with renal artery stenosis have triggered off controversy and debate among clinicians dealing with renovascular disease. The main reason underlying this ongoing controversy may be the heterogeneity of the clinical entities that are normally associated with the umbrella definition of renal artery stenosis. Indeed a causal link between the stenosis and its clinical consequences (i.e. hypertension, renal failure) can often demonstrated in some entities, such as fibromuscular dysplasia, truncal stenosis or arterial stenosis in the transplanted kidney, which can be defined as pure renal artery stenosis. On the contrary, the entity generally called ostial stenosis is a disease of the abdominal aorta where it encroaches the ostium of the renal artery at the end of a long process involving the entire vascular tree. Patients affected by ostial stenosis also suffer from generalized atherosclerosis, and kidney damage is often caused by the atherosclerotic environment with the stenosis acting as an innocent bystander. This may account for the low rate of renal function recovery in subjects with ostial stenosis. In our view, keeping the different entities separate along with a careful understanding of the mechanisms underpinning renal damage, particularly the intrarenal activation of the renin angiotensin system which in turn induces renal inflammation and oxidative stress, may enable clinicians to make the right decisions in regard to revascularization.

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“…Neovascularisation appears to be a compensatory response, which acts to maintain cortical perfusion in the face of altered vascular function [ 62 ]. On the other hand, hypercholesterolemia exacerbates the effects of renal artery stenosis on oxidative stress, infl ammation, fi brosis, and tubular and vascular dysfunction (see details discussed next) [ 63 ]. The observations of a relatively poor correlation between stenosis severity and renal dysfunction in RVD [ 64 ] and that revascularization in RVD is not always effective in restoring renal dysfunction and fails to reverse vascular remodeling [ 40 , 65 ], provide additional evidence that factors beyond the stenosis itself are critical in progression of renal dysfunction.…”

Section: Pathophysiology Of the Chronically Post-stenotic Kidney Expementioning

confidence: 99%

Blood Flow, Oxygenation, and Oxidative Stress in the Post-stenotic Kidney

Evans

O’Connor

2014

Renal Vascular Disease

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Renal ischemia, hypoxia and oxidative stress progress together over the course of renovascular disease, and thus appear to operate in a vicious pathological triangle. Renal ischemia is initially driven by the mechanical effect of the stenosis, and maintained in the medium term chiefl y by activation of the systemic and intrarenal renin-angiotensin systems. In the longer term, ischemia is exacerbated by infl ammation, fi brosis and microvascular rarefaction, at least partly driven by signaling cascades initiated by oxidative stress and tissue hypoxia. Oxidative stress in renovascular disease is initially driven by activation of the renin-angiotensin system, but other factors, such as the pro-oxidant effects of uremic toxins, likely also contribute in the longer term. Oxidative stress drives ischemia by the direct vasoconstrictor effects of reactive oxygen species such as superoxide, and through reduced bioavailability of the vasodilator nitric oxide. This microvascular dysfunction appears to be a major driver of microvascular remodeling and rarefaction. Ischemia drives tissue hypoxia by reducing oxygen delivery to tissue. Oxidative stress and the resultant reduction in nitric oxide bioavailability also promote hypoxia by reducing the efficiency of oxygen utilization in mitochondria. Reduced glomerular fi ltration leads to reduced renal oxygen consumption, so provides some protection against the development of tissue hypoxia, at least in mild or early stage renovascular disease. But, eventually, homeostasis of tissue oxygenation cannot be maintained, and tissue hypoxia ensues.

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Early atherosclerosis aggravates the effect of renal artery stenosis on the swine kidney

Cited by 31 publications

References 24 publications

Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation

Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation

When stenting in renal artery stenosis? Update on pathophysiology of ischemic nephropathy and management strategies

Blood Flow, Oxygenation, and Oxidative Stress in the Post-stenotic Kidney

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