S-EPMC4016960 - Extrarenal atherosclerotic disease blunts renal recovery in patients with renovascular hypertension. - OmicsDI

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Extrarenal atherosclerotic disease blunts renal recovery in patients with renovascular hypertension.

ABSTRACT: 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.

SUBMITTER: Khangura KK

PROVIDER: S-EPMC4016960 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Extrarenal atherosclerotic disease blunts renal recovery in patients with renovascular hypertension.

Khangura Kirandeep K KK Eirin Alfonso A Kane Garvan C GC Misra Sanjay S Textor Stephen C SC Lerman Amir A Lerman Lilach O LO

Journal of hypertension 20140601 6

<h4>Background</h4>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.<h4>Methods</h4>Patients with ARVD who underwent echocardiography a ...[more]

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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.

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