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Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease.

ABSTRACT: Background: Increased arterial stiffness and vascular endothelial dysfunction are important nontraditional cardiovascular risk factors evident in patients with CKD. Vascular oxidative stress and inflammation may contribute to vascular dysfunction in CKD, but direct evidence is lacking.

Methods: We assessed carotid-femoral pulse-wave velocity (arterial stiffness) and brachial artery flow-mediated dilation (vascular endothelial function) in participants with moderate-to-severe CKD (eGFR 15-59 ml/min per 1.73 m²) and in healthy controls. Change in brachial artery flow-mediated dilation after an acute infusion of ascorbic acid to inhibit vascular oxidative stress (versus saline) was also measured. Protein expression of vascular endothelial cells collected from a peripheral vein and ELISAs to assess circulating markers were also performed.

Results: A total of 64 participants with CKD (mean±SD, 65±8 years) and 17 healthy controls (60±5 years) were included. Carotid-femoral pulse-wave velocity was greater in participants with CKD compared with healthy controls (1071±336 versus 732±128 cm/s; P<0.001). Brachial artery flow-mediated dilation was lower in participants with CKD compared with healthy controls (3.5%±2.8% versus 5.5%±3.2%; P=0.02). Circulating inflammation markers (C-reactive protein and IL-6) were elevated in the CKD group (P?0.02). Endothelial cell protein expression of NADPH (intensity versus human umbilical vein endothelial cell control, 1.48±0.28 versus 1.25±0.31; P=0.05) was greater in participants with CKD. However, ascorbic acid significantly improved brachial artery flow-mediated dilation in control participants (saline, 5.5±3.2; ascorbic acid, 6.8±3.6); as compared with participants with CKD (saline, 3.5±2.8; ascorbic acid, 3.6±3.2) (group×condition interaction P=0.04), suggesting vascular oxidative stress could not be overcome with ascorbic acid in participants with CKD.

Conclusions: Vascular oxidative stress is present in CKD, which cannot be overcome with acute infusion of ascorbic acid.

SUBMITTER: Nowak KL

PROVIDER: S-EPMC7725223 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease.

Nowak Kristen L KL Jovanovich Anna A Farmer-Bailey Heather H Bispham Nina N Struemph Taylor T Malaczewski Mikaela M Wang Wei W Chonchol Michel M

Kidney360 20200625 6

<h4>Background</h4>Increased arterial stiffness and vascular endothelial dysfunction are important nontraditional cardiovascular risk factors evident in patients with CKD. Vascular oxidative stress and inflammation may contribute to vascular dysfunction in CKD, but direct evidence is lacking.<h4>Methods</h4>We assessed carotid-femoral pulse-wave velocity (arterial stiffness) and brachial artery flow-mediated dilation (vascular endothelial function) in participants with moderate-to-severe CKD (eG ...[more]

PMID: 33305290

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Project description:BACKGROUND AND OBJECTIVES:Both increased arterial stiffness and vascular endothelial dysfunction are evident in patients with autosomal dominant polycystic kidney disease, even early in the course of the disease when kidney function in preserved. Vascular dysfunction in autosomal dominant polycystic kidney disease is thought to be related to vascular oxidative stress and inflammation, but direct evidence is lacking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We assessed carotid-femoral pulse-wave velocity (arterial stiffness) and brachial artery flow-mediated dilation (vascular endothelial function) in participants with early-stage autosomal dominant polycystic kidney disease (eGFR?60 ml/min per 1.73 m2) and a history of controlled hypertension and in healthy controls. Brachial artery flow-mediated dilation was also assessed after infusion of ascorbic acid to inhibit vascular oxidative stress compared with saline. Vascular endothelial cells were collected from a peripheral vein to measure expression of proteins, and circulating markers were also assessed by ELISA or liquid chromatography-tandem mass spectrometry. RESULTS:In total, 61 participants with autosomal dominant polycystic kidney disease (34±9 years old [mean±SD]) and 19 healthy controls (30±5 years old) were studied. Carotid-femoral pulse-wave velocity was higher in participants with autosomal dominant polycystic kidney disease compared with healthy controls (650±131 versus 562±81 cm/s; P=0.007). Brachial artery flow-mediated dilation was 8.2%±5.8% in participants with autosomal dominant polycystic kidney disease and 10.8%±4.7% in controls (P=0.08). Among participants with autosomal dominant polycystic kidney disease, flow-mediated dilation increased from 7.7%±4.5% to 9.4%±5.2% with ascorbic acid, a difference of 1.72 (95% confidence interval, 0.80 to 2.63), whereas in control participants, flow-mediated dilation decreased nonsignificantly from 10.8%±4.7% to 10.6%±5.4%, a difference of -0.20 (95% confidence interval, -1.24 to 0.84; P interaction =0.02). Endothelial cell protein expression of NF-?B was greater in participants with autosomal dominant polycystic kidney disease (0.48±0.12 versus 0.41±0.10 [intensity versus human umbilical vein endothelial cell control]; P=0.03). However, circulating oxidative stress markers and bioactive lipid mediators did not significantly differ according to the autosomal dominant polycystic kidney disease diagnosis. CONCLUSIONS:These results provide support for the hypothesis that vascular oxidative stress and inflammation develop with autosomal dominant polycystic kidney disease. PODCAST:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_09_18_CJASNPodcast_18_10_.mp3.

Project description:This study sought to evaluate whether impaired vasodilator function, an early manifestation of coronary artery disease, which precedes angiographic stenosis, accounts for increased risk among patients with moderate to severe renal dysfunction.Patients with renal dysfunction are at increased risk of adverse cardiac outcomes, even in the absence of overt myocardial ischemia or infarction.We included 866 consecutive patients with moderate to severe renal dysfunction referred for rest and stress myocardial perfusion positron emission tomography and followed them for a median of 1.28 years (interquartile range: 0.64 to 2.34). Regional myocardial perfusion abnormalities were assessed by semiquantitative visual analysis of positron emission tomography images. Rest and stress myocardial blood flow were calculated using factor analysis and a 2-compartment kinetic model; they were also used to compute coronary flow reserve (stress/rest myocardial blood flow). The primary endpoint was cardiac death.Overall, 3-year cardiac mortality was 16.2%. After adjusting for clinical risk, left ventricular ejection fraction, as well as the magnitude of scar and/or ischemia, coronary flow reserve below the median (<1.5) was associated with a 2.1-fold increase in the risk of cardiac death (95% confidence interval [CI]: 1.3 to 3.5, p = 0.004). Incorporation of coronary flow reserve into cardiac death risk assessment models resulted in an increase in the C-index from 0.75 to 0.77 (p = 0.05) and in a net reclassification improvement of 0.142 (95% CI: 0.076 to 0.219). Among patients at intermediate risk based on all data other than coronary flow reserve, the net reclassification improvement was 0.489 (95% CI: 0.192 to 0.836). Corresponding improvements in risk assessment for mortality from any cause were also demonstrated.The presence of coronary vascular dysfunction in patients with moderate to severe renal dysfunction, as assessed by positron emission tomography, is a powerful, independent predictor of cardiac mortality and provides meaningful incremental risk stratification over conventional markers of clinical risk.

Dataset Information

Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease.

Publications

Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease.

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