S-EPMC7347430 - Peristenotic Collateral Circulation in Atherosclerotic Renovascular Disease: Association With Kidney Function and Response to Treatment. - OmicsDI

Unknown

Dataset Information

Peristenotic Collateral Circulation in Atherosclerotic Renovascular Disease: Association With Kidney Function and Response to Treatment.

ABSTRACT: The significance of peristenotic collateral circulation (PCC) development around a stenotic renal artery is unknown. We tested the hypothesis that PCC is linked to loss of kidney function and recovery potential in patients with atherosclerotic renovascular disease (ARVD). Thirty-four patients with ARVD were assigned to medical-therapy with or without revascularization based on clinical indications. The PCC was visualized using multidetector computed tomography and defined relative to segmental arteries in patients with essential hypertension. PCC number before and 3 months after treatment was correlated with various renal parameters. Thirty-four stenotic kidneys from 30 patients were analyzed. PCC number correlated inversely with kidney volume. ARVD-stenotic kidneys with baseline PCC (collateral ARVD [C-ARVD], n=13) associated with elevated 24-hour urine protein and stenotic kidney vein level of tumor necrosis factor-α, lower single-kidney volume and blood flow, and greater hypoxia than in stenotic kidneys with no PCC (no collateral ARVD [NC-ARVD], n=17). Revascularization (but not medical-therapy alone) improved stenotic kidney function and reduced inflammation in both NC-ARVD and C-ARVD. In C-ARVD, revascularization also increased stenotic kidney volume, blood flow, and oxygenation to levels comparable to NC-ARVD, and induced PCC regression. However, revascularization improved systolic blood pressure, plasma renin activity, and filtration fraction only in NC-ARVD. Therefore, patients with C-ARVD have greater kidney dysfunction, atrophy, hypoxia, and inflammation compared with patients with NC-ARVD, suggesting that PCC does not effectively protect the stenotic kidney in ARVD. Renal artery revascularization improved in C-ARVD stenotic kidney function, but not hypertension or renin-angiotensin system activation. These observations may help direct management of patients with ARVD.

SUBMITTER: Afarideh M

PROVIDER: S-EPMC7347430 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

Project description:Atherosclerotic renovascular disease is a combination of renal artery stenosis and renal ischemia. Blood pressure does not rise until the stenosis is 60% or greater. Disease of both large and small blood vessels is often accompanied by the loss of glomerular filtration rate. Activation of the renin-angiotensin-aldosterone system leads to vasoconstriction and salt retention. Risk factors for atherosclerotic renovascular disease include long-standing hypertension, diabetes, smoking and dyslipidemia. The prevalence of the condition in patients with hypertension resistant to two medications is 20%. As yet, there is no single ideal screening test or evidence-based recommended screening algorithm. Magnetic resonance angiography and computed tomography angiography are noninvasive and have high sensitivity and specificity, but also have high costs associated with them. The captopril renal scan has low sensitivity and specificity in people with renal disease (the population most likely to require the test). Doppler ultrasonography has high sensitivity and specificity in experienced hands, and the renal resistance index, which can easily be added to this test, can identify those with microvascular disease who may not benefit from revascularization. The best determinant of patient outcome is not the degree of renal artery stenosis but the degree of renal parenchymal disease. To date, renal revascularization has not been associated with improved renal survival compared with medical treatment alone. Today, the approach to atherosclerotic renovascular disease is determined by the patient's blood pressure and renal function; possibly, in the future, it will be determined by the result of the renal resistance index as part of a screening algorithm. If the blood pressure is uncontrollable or the renal function is deteriorating, the patient should be considered for renal revascularization initially, with a percutaneous endovascular stent. The management of hypertension involves the use of combinations of antihypertensive agents at doses sufficient to control blood pressure. Medical management also includes aggressive lipid-lowering therapy.

Project description:AimsThe mechanisms responsible for renal injury in atherosclerotic renovascular disease (ARVD) are incompletely understood, and few therapeutic options are available to reverse it. We hypothesized that chronic renal damage involves mitochondrial injury, and that mitochondrial protection would reduce renal fibrosis and dysfunction in ARVD pigs.Methods and resultsDomestic pigs were studied after 10 weeks of ARVD or sham, treated for the last 4 weeks with daily subcutaneous injections (5 days/week) of vehicle or Bendavia (0.1 mg/kg), a tetrapeptide that preserves cardiolipin content in the mitochondrial inner membrane. Single-kidney haemodynamics and function were studied using fast-computer tomography, oxygenation using blood oxygen level-dependent magnetic resonance imaging, microvascular architecture, oxidative stress, and fibrosis ex vivo. Cardiolipin content was assessed using mass spectrometry and staining. Renal endothelial function was studied in vivo and ex vivo. In addition, swine renal artery endothelial cells incubated with tert-butyl hydroperoxide were also treated with Bendavia. Stenotic-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) decreased in ARVD + Vehicle compared with normal (318.8 ± 61.0 vs. 553.8 ± 82.8 mL/min and 48.0 ± 4.0 vs. 84.0 ± 3.8 mL/min, respectively) associated with loss of cardiolipin, intra-renal microvascular rarefaction, and hypoxia. Bendavia restored cardiolipin content in ARVD and improved vascular density, oxygenation, RBF (535.1 ± 24.9 mL/min), and GFR (86.6 ± 11.2 mL/min). Oxidative stress and fibrosis were ameliorated, and renovascular endothelial function normalized both in vivo and in vitro.ConclusionPreservation of mitochondrial cardiolipin attenuated swine stenotic-kidney microvascular loss and injury, and improved renal oxygenation, haemodynamics, and function. These observations implicate mitochondrial damage in renal deterioration in chronic experimental ARVD, and position the mitochondria as a central therapeutic target.

Project description:PurposeThis report describes the change in atherosclerotic renovascular disease (AS-RVD) among hypertensive adults referred for renal duplex sonography (RDS) scan.MethodsFrom Oct 1993 through July 2008, 20,994 patients had RDS at our center. A total of 434 hypertensive patients with two or more RDS exams without intervention comprised the study cohort. Patient demographics (blood pressures, medications, serum creatinine levels, and data from RDS) were collected. Analyses of longitudinal changes in Doppler scan parameters, blood pressures, and renal function were performed by fitting linear growth-curve models. After confirming the linearity of change in Doppler scan parameters among patients with variable number of studies, estimates of mean slopes were calculated using maximum likelihood techniques. For changes in renal function, quadratic growth curves were required to describe longitudinal change.ResultsA total of 434 subjects (212 men [49%] and 222 women [51%]; mean age, 64.6 +/- 12.2 years) provided 1351 studies (mean, 3.2 +/- 2.4; range, 2 to 18) for 863 kidneys over a mean follow-up of 34.4 +/- 25.1 months. At baseline, 20.6% of kidneys demonstrated hemodynamically significant stenosis. On follow-up, 72 kidneys (9.1%) demonstrated anatomic progression of disease. A total of 54 kidneys (6.9%) progressed to significant stenosis and 18 (2.3%) progressed to occlusion. Controlling for progression of disease, baseline renal artery status demonstrated a strong association with baseline kidney length (P = .0006). Significant annualized change in renal length was observed (cm change/year +/- standard error of the mean [SEM]: 0.042 +/- 0.011; P = .0002) among both kidneys with and without critical disease at baseline, however, decline in length was significantly greater among kidneys exhibiting progression of renovascular disease (-0.152 +/- 0.028 cm/year; comparison of slopes between groups P = .0005). In the absence of progression, the presence or absence of critical renal artery stenosis at baseline did not affect the rate of decline in renal length. Fitted models for the natural log transform of serum creatinine demonstrated a significant increase during follow-up (P < .0001). No association was observed between change in serum creatinine and baseline renovascular disease status, or its progression.ConclusionA total of 32% of hypertensive adults referred for RDS demonstrated hemodynamically significant renal artery stenosis. Regardless of the presence or absence of baseline disease, a small percentage of patients demonstrated anatomic progression of AS-RVD. A total of 9.1% demonstrated anatomic progression and 2.3% progressed to occlusion. Although anatomic progression of AS-RVD was associated with an increased rate of decline in renal length, progression did not predict a decline in excretory renal function. Intervention for AS-RVD should be selective and reserved for strict indications.

Project description:Atherosclerotic renovascular disease (ARVD) is associated with high rates of coronary events and predicts mortality among patients with coronary artery disease (CAD). However, the impact of coronary atherosclerosis on renal outcomes after revascularization of ARVD is unclear. We hypothesized that CAD negatively impacts renal functional outcomes among patients with ARVD undergoing renal artery revascularization.Patients with ARVD who underwent echocardiography at Mayo Clinic, Rochester, Minnesota, USA between 2004 and 2012 were identified retrospectively and included if they had ejection fraction more than 50%. Renal and overall outcomes were compared among atherosclerotic renovascular disease patients with coronary artery disease (ARVD-C, n?=?75) and without coronary artery disease (ARVD, n?=?56), within 1 year from initial revascularization and included blood pressure control, renal function, and incident cardiovascular/cerebrovascular events.Degree of renal artery stenosis was similar in both groups. ARVD-C had higher prevalence of diabetes, peripheral artery disease (PAD), and cerebrovascular disease, and lower baseline renal function. Risk of developing end-stage renal disease was higher in ARVD-C (11 vs. 2%, P?=?0.05). Despite better control of blood pressure and cholesterol levels, renal function postrevascularization worsened in 15% of ARVD-C compared with 2% of ARVD (P?=?0.01). Differences in clinical outcomes remained statistically significant after adjustment for covariables, including sex, baseline blood pressure, renal function, underlying diabetes, cholesterol levels, and medications. Similar differences in clinical outcomes were also associated with PAD and cerebrovascular disease.CAD in patients with ARVD is a predictor of worse outcomes after renal revascularization, likely reflecting diffuse atherosclerotic disease. Further studies are needed to develop strategies to manage patients with vascular comorbidities and improve their outcomes.

Project description:Following an arterial occlusion outward remodeling of pre-existent inter-connecting arterioles occurs by proliferation of vascular smooth muscle and endothelial cells. This is initiated by deformation of the endothelial cells through increased pulsatile fluid shear stress (FSS) caused by the steep pressure gradient between the high pre-occlusive and the very low post-occlusive pressure regions that are interconnected by collateral vessels. Shear stress leads to the activation and expression of all NOS isoforms and NO production, followed by endothelial VEGF secretion, which induces MCP-1 synthesis in endothelium and in the smooth muscle of the media. This leads to attraction and activation of monocytes and T-cells into the adventitial space (peripheral collateral vessels) or attachment of these cells to the endothelium (coronary collaterals). Mononuclear cells produce proteases and growth factors to digest the extra-cellular scaffold and allow motility and provide space for the new cells. They also produce NO from iNOS, which is essential for arteriogenesis. The bulk of new tissue production is carried by the smooth muscles of the media, which transform their phenotype from a contractile into a synthetic and proliferative one. Important roles are played by actin binding proteins like ABRA, cofilin, and thymosin beta 4 which determine actin polymerization and maturation. Integrins and connexins are markedly up-regulated. A key role in this concerted action which leads to a 2-to-20 fold increase in vascular diameter, depending on species size (mouse versus human) are the transcription factors AP-1, egr-1, carp, ets, by the Rho pathway and by the Mitogen Activated Kinases ERK-1 and -2. In spite of the enormous increase in tissue mass (up to 50-fold) the degree of functional restoration of blood flow capacity is incomplete and ends at 30% of maximal conductance (coronary) and 40% in the vascular periphery. The process of arteriogenesis can be drastically stimulated by increases in FSS (arterio-venous fistulas) and can be completely blocked by inhibition of NO production, by pharmacological blockade of VEGF-A and by the inhibition of the Rho-pathway. Pharmacological stimulation of arteriogenesis, important for the treatment of arterial occlusive diseases, seems feasible with NO donors.