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      Longitudinal association of carotid endothelial shear stress with renal function decline in aging adults with normal renal function: A population-based cohort study

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          Abstract

          The aim of this study was to investigate the associations between carotid wall shear stress (WSS) and renal function impairment (RFI) and albuminuria in aging adults. A total of 1,447 subjects aged 60 years and older with normal estimated glomerular filtration rate (eGFR ≥ 60 mL·min −1·1.72 m −2) and albumin/creatinine ratio (ACR < 30 mg·g −1) were enrolled between April 2007 and October 2009 in the Shandong area, China. Carotid WSS was assessed at baseline, and eGFR, which is based on serum creatinine and cystatin C, and ACR were assessed at baseline and at the annual follow-up visits. After an average of 62.9 months of follow-up, the reduction in eGFR and the increase in ACR were significantly higher in the Q 1+2+3 group than the Q 4 group, as classified by either the interquartile of the mean WSS or the interquartile of the peak WSS after adjustment for multi-variabilities, including the average blood pressures at every annual visit and baseline eGFR and ACR. For groups classified by mean WSS, the hazard ratios (95% confidence intervals) were 3.45 (1.36–8.75, p = 0.008) in the incident RFI and 3.24 3.22 (1.37–7.57, p = 0.009) in the incident albuminuria for the Q 1+2+3 group compared with the Q 4 group. Similar results were observed among groups classified by peak WSS. The Q 1+2+3 group was associated with endothelial dysfunction and inflammation with respect to the Q 4 group as classified by mean or peak WSS. The results indicate that carotid WSS plays an important role in RFI and albuminuria progression in aging adults. Lower WSS was associated with a higher risk of RFI and albuminuria compared with higher WSS.

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          Increased central venous pressure is associated with impaired renal function and mortality in a broad spectrum of patients with cardiovascular disease.

          We sought to investigate the relationship between increased central venous pressure (CVP), renal function, and mortality in a broad spectrum of cardiovascular patients. The pathophysiology of impaired renal function in cardiovascular disease is multifactorial. The relative importance of increased CVP has not been addressed previously. A total of 2,557 patients who underwent right heart catheterization in the University Medical Center Groningen, the Netherlands, between January 1, 1989, and December 31, 2006, were identified, and their data were extracted from electronic databases. Estimated glomerular filtration rate (eGFR) was assessed with the simplified modification of diet in renal disease formula. Mean age was 59 +/- 15 years, and 57% were men. Mean eGFR was 65 +/- 24 ml/min/1.73 m(2), with a cardiac index of 2.9 +/- 0.8 l/min/m(2) and CVP of 5.9 +/- 4.3 mm Hg. We found that CVP was associated with cardiac index (r = -0.259, p < 0.0001) and eGFR (r = -0.147, p < 0.0001). Also, cardiac index was associated with eGFR (r = 0.123, p < 0.0001). In multivariate analysis CVP remained associated with eGFR (r = -0.108, p < 0.0001). In a median follow-up time of 10.7 years, 741 (29%) patients died. We found that CVP was an independent predictor of reduced survival (hazard ratio: 1.03 per mm Hg increase, 95% confidence interval: 1.01 to 1.05, p = 0.0032). Increased CVP is associated with impaired renal function and independently related to all-cause mortality in a broad spectrum of patients with cardiovascular disease.
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            Endothelial dysfunction: a comprehensive appraisal

            The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the vasodilatation produced by drugs that are NO donors, such as nitroglycerine, called "endothelium independent". The vasodilatation is quantified by measuring the arterial diameter with high resolution ultrasonography. Laser-Doppler techniques are now starting to be used that also consider tissue perfusion. There is so much proof about endothelial dysfunction that it is reasonable to believe that there is diagnostic and prognostic value in its evaluation for the late outcome. There is no doubt that endothelial dysfunction contributes to the initiation and progression of atherosclerotic disease and could be considered an independent vascular risk factor. Although prolonged randomized clinical trials are needed for unequivocal evidence, the data already obtained allows the methods of evaluation of endothelial dysfunction to be considered useful in clinical practice and have overcome the experimental step, being non-invasive increases its value making it use full for follow-up of the progression of the disease and the effects of different treatments.
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              Mechanism of endothelial dysfunction in chronic kidney disease.

              Endothelium is the largest organ in the body strategically located between the wall of blood vessels and the blood stream. The human body contains approximately 10(13) endothelial cells weighing approximately 1kg, and covering a surface area of 4000 to 7000m(2) equivalent to the soccer playground. Hypertension and shear stress, inflammation, diabetes-associated factors such as advanced glycated end products, and uremic toxins are some of the prevalent risk factors of endothelial dysfunction in chronic kidney disease. In renal failure endothelial dysfunction and atherosclerosis are almost universal, as well as cardiovascular complications. Endothelial cell damage or injury is invariably associated with such clinical conditions as thrombosis, hypertension, renal failure and atherosclerosis and may be also responsible for accelerated atherosclerosis in patients with chronic renal failure. Traditional risk factor cannot explain the high prevalence and incidence of cardiovascular disease in chronic kidney disease, therefore other non-traditional risk factors such as endothelial dysfunction, oxidative stress or insulin resistance have increasingly been studied. In this review paper mechanism of endothelial dysfunction, including the role of nitric oxide pathway, adipocytokines and hemodialysis-induced endothelial dysfunction is discussed. Copyright 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                zhendongliu876@126.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                14 February 2019
                14 February 2019
                2019
                : 9
                : 2051
                Affiliations
                [1 ]GRID grid.410587.f, Cardio-Cerebrovascular Control and Research Center, Institute of Basic Medicine, Shandong Academy of Medical Sciences, ; Jinan, Shandong 250062 China
                [2 ]Department of Community, Lanshan District People Hospital, Linyi, Shandong 276002 China
                [3 ]GRID grid.452704.0, Department of Cardiology, , The Second Hospital of Shandong University, ; Jinan, Shandong 250000 China
                Article
                38470
                10.1038/s41598-018-38470-x
                6376032
                30765747
                f5ec718b-c62a-4114-820d-255b652fb073
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 5 September 2018
                : 27 December 2018
                Funding
                Funded by: the Project of Healthy and Family Planning Commission of Shandong Province (grant number: 2017WS076); the Project of Shandong Academy of Medical Sciences (grant number: 2017-32)
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81500232
                Award ID: 81470489
                Award ID: 81670432
                Award Recipient :
                Funded by: the Key Research and Development Project of Shandong Province (grant numbers: 2017GSF18169)
                Funded by: Natural Science Foundation of Shandong Province, China (grant numbers: ZR2014HL012)
                Funded by: Natural Science Foundation of Shandong Province, China (grant numbers: ZR2016HM82), the Key Research and Development Project of Shandong Province (grant numbers: 2017GSF218060)
                Funded by: FundRef https://doi.org/10.13039/501100007129, Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation);
                Award ID: ZR2014HM098
                Award Recipient :
                Funded by: Natural Science Foundation of Shandong Province, China (grant numbers: ZR2014HM098,), the Key Research and Development Project of Shandong Province (grant numbers: 2018GSF118044), and The Innovation Project of Shandong Academy of Medical Sciences.
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