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      Ambulatory Blood Pressure in Chronic Kidney Disease: Ready for Prime Time?

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          Abstract

          Hypertension is common in patients with chronic kidney disease (CKD) and is the most important modifiable risk factor for CKD progression and adverse cardiovascular events in these patients. Diagnosis and successful management of hypertension are critically dependent on accurate blood pressure (BP) measurement. This is most relevant to CKD patients, in whom BP control is difficult to achieve and in whom early antihypertensive treatment is imperative to prevent kidney and cardiovascular complications. Accumulated data indicate that ambulatory blood pressure monitoring (ABPM) is better in detecting hypertension than office BP measurement. ABPM is also a superior prognostic marker compared with office BP and has successfully identified hypertensive CKD patients at increased risk. Additionally, ABPM provides information on circadian BP variation and short-term BP variability, which is associated with cardiovascular and renal outcomes. This paper reviews the evidence for the usefulness of ABPM in detection and management of hypertension in CKD patients and discusses our current understanding of the pathophysiology of altered circadian BP rhythm and variability in CKD and the role of abnormal BP patterns detected by ABPM in relation to outcomes in CKD. In addition, this Review examines the emerging role of antihypertensive chronotherapy to tailor BP management to the circadian BP pattern abnormality detected by 24-hour ABPM.

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          Sympathetic-nerve activity during sleep in normal subjects.

          The early hours of the morning after awakening are associated with an increased frequency of events such as myocardial infarction and ischemic stroke. The triggering mechanisms for these events are not clear. We investigated whether autonomic changes occurring during sleep, particularly rapid-eye-movement (REM) sleep, contribute to the initiation of such events. We measured blood pressure, heart rate, and sympathetic-nerve activity (using microneurography, which provides direct measurements of efferent sympathetic-nerve activity related to muscle blood vessels) in eight normal subjects while they were awake and while in the five stages of sleep. The mean (+/- SE) amplitude of bursts of sympathetic-nerve activity and levels of blood pressure and heart rate declined significantly (P < 0.001), from 100 +/- 9 percent, 90 +/- 4 mm Hg, and 64 +/- 2 beats per minute, respectively, during wakefulness to 41 +/- 9 percent, 80 +/- 4 mm Hg, and 59 +/- 2 beats per minute, respectively, during stage 4 of non-REM sleep. Arousal stimuli during stage 2 sleep elicited high-amplitude deflections on the electroencephalogram (called K complexes), which were frequently associated with bursts of sympathetic-nerve activity and transient increases in blood pressure. During REM sleep, sympathetic-nerve activity increased significantly (to 215 +/- 11 percent; P < 0.001) and the blood pressure and heart rate returned to levels similar to those during wakefulness. Momentary restorations of muscle tone during REM sleep (REM twitches) were associated with cessation of sympathetic-nerve discharge and surges in blood pressure. REM sleep is associated with profound sympathetic activation in normal subjects, possibly linked to changes in muscle tone. The hemodynamic and sympathetic changes during REM sleep could play a part in triggering ischemic events in patients with vascular disease.
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            Sympathetic overactivity in patients with chronic renal failure.

            Hypertension is a frequent complication of chronic renal failure, but its causes are not fully understood. There is indirect evidence that increased activity of the sympathetic nervous system might contribute to hypertension in patients with end-stage renal disease, but sympathetic-nerve discharge has not been measured directly in patients or animals with chronic renal failure. We recorded the rate of postganglionic sympathetic-nerve discharge to the blood vessels in skeletal muscle by means of microelectrodes inserted into the peroneal nerve in 18 patients with native kidneys who were undergoing long-term treatment with hemodialysis (of whom 14 had hypertension), 5 patients receiving hemodialysis who had undergone bilateral nephrectomy (of whom 1 had hypertension), and 11 normal subjects. RESULTS. The mean (+/- SE) rate of sympathetic-nerve discharge was 2.5 times higher in the patients receiving hemodialysis who had not undergone nephrectomy than in the normal subjects (58 +/- 3 vs. 23 +/- 3 bursts per minute, P < 0.01). In contrast, the rate of sympathetic-nerve discharge was similar in the patients receiving hemodialysis who had undergone bilateral nephrectomy (21 +/- 6 bursts per minute) and the normal subjects. The rate of sympathetic-nerve discharge in the patients receiving hemodialysis who had not undergone nephrectomy was also significantly higher (P < 0.01) than that in the patients with bilateral nephrectomy, and it was accompanied in the former group by higher values for vascular resistance in the calf (45 +/- 4 vs. 22 +/- 4 units, P < 0.05) and mean arterial pressure (106 +/- 4 vs. 76 +/- 14 mm Hg, P < 0.05). The rate of sympathetic-nerve discharge was not correlated with either plasma norepinephrine concentrations or plasma renin activity. Chronic renal failure may be accompanied by reversible sympathetic activation, which appears to be mediated by an afferent signal arising in the failing kidneys.
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              Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture).

              Endothelial cells synthesize and release various factors that regulate angiogenesis, inflammatory responses, hemostasis, as well as vascular tone and permeability. Endothelial dysfunction has been associated with a number of pathophysiological processes. Oxidative stress appears to be a common denominator underlying endothelial dysfunction in cardiovascular diseases. However, depending on the pathology, the vascular bed studied, the stimulant, and additional factors such as age, sex, salt intake, cholesterolemia, glycemia, and hyperhomocysteinemia, the mechanisms underlying the endothelial dysfunction can be markedly different. A reduced bioavailability of nitric oxide (NO), an alteration in the production of prostanoids, including prostacyclin, thromboxane A2, and/or isoprostanes, an impairment of endothelium-dependent hyperpolarization, as well as an increased release of endothelin-1, can individually or in association contribute to endothelial dysfunction. Therapeutic interventions do not necessarily restore a proper endothelial function and, when they do, may improve only part of these variables.
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                Author and article information

                Journal
                101684752
                45366
                Kidney Int Rep
                Kidney Int Rep
                Kidney international reports
                2468-0249
                23 January 2017
                4 June 2016
                July 2016
                01 July 2017
                : 1
                : 2
                : 94-104
                Affiliations
                [1 ]Division of Renal Diseases and Hypertension, The George Washington University, Washington, DC, USA
                [2 ]University of Utah School of Medicine, Kidney and Liver Clinic, Salt Lake City, Utah, USA
                [3 ]University Hospitals Case Medical Center, Department of Medicine-Hypertension, Cleveland, Ohio, USA
                Author notes
                Correspondence: Dominic S. Raj, Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA. draj@ 123456mfa.gwu.edu
                Article
                NIHMS843890
                10.1016/j.ekir.2016.05.001
                5283800
                28164170
                a48c7106-170e-4e4e-b65e-75c60f01eae0

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Article

                ambulatory blood pressure monitoring,cardiovascular disease,chronic kidney disease,circadian rhythm,hypertension

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