Abstract-We reported previously that urinary angiotensinogen (UAGT) levels provide a specific index of the intrarenal renin-angiotensin system (RAS) status in angiotensin II-dependent hypertensive rats. To study this system in humans, we recently developed a human angiotensinogen ELISA. To test the hypothesis that UAGT is increased in hypertensive patients, we recruited 110 adults. Four subjects with estimated glomerular filtration levels Ͻ30 mL/min per 1.73 m 2 were excluded because previous studies have already shown that UAGT is highly correlated with estimated glomerular filtration in this stage of chronic kidney disease. Consequently, 106 paired samples of urine and plasma were analyzed from 70 hypertensive patients (39 treated with RAS blockers [angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers; systolic blood pressure: 139Ϯ3 mm Hg] and 31 not treated with RAS blockers [systolic blood pressure: 151Ϯ4 mm Hg]) and 36 normotensive subjects (systolic blood pressure: 122Ϯ2 mm Hg). UAGT, normalized by urinary concentrations of creatinine, were not correlated with race, gender, age, height, body weight, body mass index, fractional excretion of sodium, plasma angiotensinogen levels, or estimated glomerular filtration. However, UAGT/urinary concentration of creatinine was significantly positively correlated with systolic blood pressure, diastolic blood pressure, urinary albumin:creatinine ratio (rϭ0.5994), and urinary protein:creatinine ratio (rϭ0.4597). UAGT/urinary concentration of creatinine was significantly greater in hypertensive patients not treated with RAS blockers (25.00Ϯ4.96 g/g) compared with normotensive subjects (13.70Ϯ2.33 g/g). Importantly, patients treated with RAS blockers exhibited a marked attenuation of this augmentation (13.26Ϯ2.60 g/g). These data indicate that UAGT is increased in hypertensive patients, and treatment with RAS blockers suppresses UAGT, suggesting that the efficacy of RAS blockade to reduce the intrarenal RAS activity can be assessed by measurements of UAGT.

Abstract-Uric acid has been proposed as an important risk factor in the development of primary hypertension in humans.However, limited information is available linking childhood uric acid levels and blood pressure levels in adulthood. This study examined 334 whites and 243 blacks enrolled in the Bogalusa Heart Study as children aged 5 to 17 years and as adults aged 18 to 35 years. The average follow-up period was 12 years. Childhood uric acid was significantly correlated with childhood and adult blood pressure, both systolic and diastolic. In a multivariate regression analysis, adjusting for age, sex, race, childhood body mass index, childhood uric acid levels, and change in levels of uric acid were significant predictors of adult diastolic blood pressure, whereas change in uric acid was a significant predictor of adult systolic blood pressures. In conclusion, elevated childhood serum uric acid levels are associated with increased blood pressure beginning in childhood and higher blood pressure levels that persist into adulthood, in males and females, whites and blacks, suggesting that early elevations in serum uric acid levels may play a key role in the development of human hypertension. (Hypertension. 2005;45:34-38.)Key Words: uric acid Ⅲ blood pressure Ⅲ children E ssential hypertension affects up to 25% of adults and significantly increases the risk of myocardial infarction, stroke, congestive heart failure, and renal failure. 1,2 There are significant race and gender differences in the incidence of hypertension, and the disease process has been clearly shown to begin in childhood. 3 During the past several years, several clinical and laboratory studies have suggested that uric acid might be an important factor in the development of primary hypertension in humans. Hyperuricemia has been demonstrated to predict and be an independent risk factor for hypertension in adults. 4,5 Also, 25% to 40% of adult patients with untreated hypertension have hyperuricemia (Ͼ386.6 mol/L [6.5 mg/dL]). 6,7 Earlier studies in children and young adults showed uric acid levels were higher in white subjects and were associated with higher diastolic blood pressure (DBP) and lean body mass. 8,9 Recently, Feig and Johnson 10 demonstrated a significant correlation between elevated uric acid levels (Ͼ327 mol/L [5.5 mg/dL]) and blood pressure (BP) in children and adolescents. However, to date, there is a paucity of information on the relationship between childhood uric acid levels and adult BP. Using the longitudinal data from the Bogalusa Heart Study, a community-based study of the cardiovascular risk factors beginning in childhood, we examined the predictability of BP in adults from childhood uric acid levels. 11Understanding the early stages of this relationship will help in the early identification and prevention of hypertension. Materials and Methods Study PopulationThe Bogalusa Heart Study consists of multiple cross-sectional surveys of all children, aged 5 to 17 years, and multiple surveys of young adults, aged Ն18 years, in a bira...

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Background and objectives Masked hypertension and elevated nighttime BP are associated with increased risk of hypertensive target organ damage and adverse cardiovascular and renal outcomes in patients with normal kidney function. The significance of masked hypertension for these risks in patients with CKD is less well defined. The objective of this study was to evaluate the association between masked hypertension and kidney function and markers of cardiovascular target organ damage, and to determine whether this relationship was consistent among those with and without elevated nighttime BP.Design, setting, participants, & measurements This was a cross-sectional study. We performed 24-hour ambulatory BP in 1492 men and women with CKD enrolled in the Chronic Renal Insufficiency Cohort Study. We categorized participants into controlled BP, white-coat, masked, and sustained hypertension on the basis of clinic and 24-hour ambulatory BP. We obtained echocardiograms and measured pulse wave velocity in 1278 and 1394 participants, respectively. ResultsThe percentages of participants with controlled BP, white-coat, masked, and sustained hypertension were 49.3%, 4.1%, 27.8%, and 18.8%, respectively. Compared with controlled BP, masked hypertension independently associated with low eGFR (23.2 ml/min per 1.73 m 2 ; 95% confidence interval, 25.5 to 20.9), higher proteinuria (+0.9 unit higher in log 2 urine protein; 95% confidence interval, 0.7 to 1.1), and higher left ventricular mass index (+2.52 g/m 2.7 ; 95% confidence interval, 0.9 to 4.1), and pulse wave velocity (+0.92 m/s; 95% confidence interval, 0.5 to 1.3). Participants with masked hypertension had lower eGFR only in the presence of elevated nighttime BP (23.6 ml/min per 1.73 m 2 ; 95% confidence interval, 26.1 to 21.1; versus 21.4 ml/min per 1.73 m 2 ; 95% confidence interval, 26.9 to 4.0, among those with nighttime BP ,120/70 mmHg; P value for interaction with nighttime systolic BP 0.002).Conclusions Masked hypertension is common in patients with CKD and associated with lower eGFR, proteinuria, and cardiovascular target organ damage. In patients with CKD, ambulatory BP characterizes the relationship between BP and target organ damage better than BP measured in the clinic alone.

Studies of hemodialysis patients have shown a U-shaped association between systolic blood pressure (SBP) and mortality. These studies have largely relied on dialysis-unit SBP measures and have not evaluated whether this U-shape also exists in advanced chronic kidney disease (CKD), prior to starting hemodialysis. We determined the association between SBP and mortality at advanced CKD and again after initiation of hemodialysis. This was a prospective study of Chronic Renal Insufficiency Cohort (CRIC) participants with advanced CKD followed through initiation of hemodialysis. We studied the association between SBP and mortality when participants: 1) had an estimated glomerular filtration rate <30 ml/min/1.73m2 (N=1,705); 2) initiated hemodialysis and had dialysis-unit SBP measures (N=403) and; 3) initiated hemodialysis and had out-of-dialysis-unit SBP measured at a CRIC study visit (N=326). Cox models adjusted for demographics, cardiovascular risk factors and dialysis parameters. A quadratic term for SBP was included to test for a U-shaped association. At advanced CKD, there was no association between SBP and mortality (HR 1.02 [95% CI: 0.98–1.07] per every 10 mm Hg increase). Among participants who started hemodialysis, a U-shaped association between dialysis-unit SBP and mortality was observed. In contrast, there was a linear association between out-of-dialysis-unit SBP and mortality (HR 1.26 [95% CI: 1.14–1.40] per every 10 mm Hg increase). In conclusion, more efforts should be made to obtain out-of-dialysis-unit SBP which may merit more consideration as a target for clinical management and in interventional trials.