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      Angiotensin Receptor Blockade and Arterial Compliance in Chronic Kidney Disease: A Pilot Study

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          Background: Almost 20 million people in the US have chronic kidney disease (CKD). Cardiovascular disease and arterial wall abnormalities are common in this population. Because angiotensin II may have adverse effects on the arterial wall, we hypothesized that an angiotensin receptor blocker (ARB) would improve arterial compliance as compared with placebo in subjects with CKD. Methods: We performed a double-blinded, placebo-controlled pilot study in which 25 subjects with stages 2 or 3 CKD and proteinuria <1 g were randomized to either the ARB, eprosartan, or placebo and titrated to achieve a goal blood pressure (BP) <130/85 mm Hg. Arterial compliance was measured at baseline and at 8 weeks. Results: Baseline characteristics were similar between the groups and included mean estimated glomerular filtration rate 63 ± 14 ml/min/1.73 m<sup>2</sup>, heart rate 76 ± 10 beats/min, BP 142 ± 12/81 ± 8 mm Hg, 64% diabetic, 44% male, and 40% white, though subjects in the eprosartan group were younger (60 ± 12 vs. 70 ± 6 years, p = 0.01). There were no significant differences between the groups in large or small artery compliance measurements either at baseline or at 8 weeks, but there was a statistically significant improvement from baseline in small artery compliance in the eprosartan group (from median 2.5 ml/mm Hg × 100 [90% CI (1.1, 4.7)] to 4.0 ml/mm Hg × 100 [90% CI (1.9, 6.7)] (p = 0.01)) not seen in the placebo group. Conclusion: Use of an ARB to achieve recommended BP is associated with improved small artery compliance in people with CKD, though larger studies are needed to confirm these findings.

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          Most cited references 11

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          Aortic pulse wave velocity index and mortality in end-stage renal disease.

          Aortic pulse wave velocity (PWV) is a strong independent predictor of overall and cardiovascular mortality in patients with end-stage renal disease (ESRD). Nevertheless, because age, blood pressure, heart rate, and gender are strong determinants of both arterial stiffness and mortality, the individual relevance of PWV measurements remains controversial. A cohort of 242 patients with ESRD undergoing hemodialysis was studied for a mean (+/- SD) duration of 78 +/- 46 months. At entry, together with standard clinical and biochemical analyses, PWV was measured using Doppler ultrasonography. On the basis of a nomogram established on 469 nonuremic subjects, a theoretical value of PWV was determined in ESRD patients according to their age, blood pressure, gender, and heart period. The PWV index (measured PWV - theoretical PWV) was then calculated for each individual ESRD patient. Based on Cox analysis, the PWV index, but neither pulse pressure nor cardiac mass, was a strong and independent predictor of both cardiovascular and overall mortality, together with age and time on dialysis before inclusion. Patients with positive (versus negative) PWV index had a twofold adjusted risk of mortality during the follow-up. Per each 1 meter/second PWV index increment, we observed a 34% (crude) and a 14% (adjusted) increase in both cardiovascular and overall mortality (P < 0.02 for all). In ESRD patients, the calculation of a PWV index provides information about cardiovascular and overall mortality risk with high predictive power, showing that PWV measurements provide discriminatory prognostic power over and above conventional cardiovascular risk factors.
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            Endothelial function and oxidative stress in renovascular hypertension.

            It has been reported that renovascular hypertension activates the renin-angiotensin system, leading to an increase in oxidative stress. We sought to determine whether renal-artery angioplasty improves endothelial dysfunction in patients with renovascular hypertension through a reduction in oxidative stress. We evaluated the response of forearm blood flow to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate, an endothelium-independent vasodilator, before and after renal-artery angioplasty in 15 subjects with renovascular hypertension and 15 controls without hypertension who were matched for age and sex. Forearm blood flow was measured with the use of a mercury-filled Silastic strain-gauge plethysmograph. The forearm blood flow in response to acetylcholine was less in subjects with renovascular hypertension than in controls, although the forearm blood flow in response to isosorbide dinitrate was similar in the two groups. Angioplasty decreased systolic and diastolic blood pressures, forearm vascular resistance, and urinary excretion of 8-hydroxy-2'-deoxyguanosine and serum malondialdehyde-modified low-density lipoprotein (LDL), indexes of oxidative stress. After angioplasty, the mean (+/-SD) forearm blood flow in response to acetylcholine was increased in the patients with renovascular hypertension (19.3+/-6.8 vs. 29.6+/-7.1 ml per minute per 100 ml, P=0.002). The increase in the maximal forearm blood flow in response to acetylcholine correlated significantly with the decrease in urinary excretion of 8-hydroxy-2'-deoxyguanosine (r=-0.51, P=0.004) and serum malondialdehyde-modified LDL (r=-0.39, P=0.02). Coinfusion of ascorbic acid (vitamin C) augmented the response of forearm blood flow to acetylcholine before angioplasty (P<0.001) but not after angioplasty. These findings suggest that excessive oxidative stress is involved, at least in part, in impaired endothelium-dependent vasodilatation in patients with renovascular hypertension.
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              Creatinine clearance, pulse wave velocity, carotid compliance and essential hypertension.

              The vascular hallmark of subjects with end-stage renal disease is increased arterial stiffness independent of blood pressure, wall stress, and cardiovascular risk factors such as hypertension, plasma glucose and cholesterol, obesity, and tobacco consumption. Whether arterial stiffness and kidney function are statistically associated in subjects with plasma creatinine < or =130 micromol/L has not yet been determined. Material. In 1290 subjects with normal or elevated blood pressure values and plasma creatinine < or =130 micromol/L, subjects were divided into three tertiles according to the calculated creatinine clearance. Blood pressure, aortic pulse wave velocity (PWV), and standard cardiovascular risk factors were determined in parallel. In 112 of the hypertensive subjects, common carotid and radial artery structure and function (high-resolution echo-Doppler techniques) also were measured. From the 1290 subjects, only the low-tertile group presented a significant negative association between PWV and creatinine clearance independently of blood pressure and standard risk factors. This association was stronger in subjects < or =55 years of age. In the 112 hypertensive subjects, carotid compliance was positively correlated to creatinine clearance even after an adjustment for age, gender, and blood pressure. At less than 55 years of age, creatinine clearance represented 20% of the variance of carotid compliance. Such findings were not observed for radial artery compliance. Increased stiffness of central arteries is statistically associated with reduced creatinine clearance in subjects with mild-to-moderate renal insufficiency, indicating that kidney alterations may interact not only with small but also large arteries, and this is independent of age, blood pressure, and standard risk factors.

                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                August 2005
                18 August 2005
                : 25
                : 4
                : 393-399
                aDivision of Nephrology, Department of Medicine, University of California-San Francisco, San Francisco, Calif., and bDepartment of Preventive Medicine, RUSH University Hypertension Center, RUSH, University Medical Center, Chicago, Ill., USA
                87211 Am J Nephrol 2005;25:393–399
                © 2005 S. Karger AG, Basel

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                Page count
                Figures: 3, Tables: 2, References: 29, Pages: 7
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                Original Report: Patient-Oriented, Translational Research


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