These findings suggest that the metabolic syndrome might be an important factor in the cause of chronic kidney disease.

Background and objectives: The Chronic Renal Insufficiency Cohort (CRIC) Study was established to examine risk factorsfor the progression of chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with CKD. We examined baseline demographic and clinical characteristics.Design, setting, participants, & measurements: Seven clinical centers recruited adults who were aged 21 to 74 yr and had CKD using age-based estimated GFR (eGFR) inclusion criteria. At baseline, blood and urine specimens were collected and information regarding health behaviors, diet, quality of life, and functional status was obtained. GFR was measured using radiolabeled iothalamate in one third of participants.Results: A total of 3612 participants were enrolled with mean age ؎ SD of 58.2 ؎ 11.0 yr; 46% were women, and 47% had diabetes. Overall, 45% were non-Hispanic white, 46% were non-Hispanic black, and 5% were Hispanic. Eighty-six percent reported hypertension, 22% coronary disease, and 10% heart failure. Mean body mass index was 32.1 ؎ 7.9 kg/m 2 , and 47% had a BP >130/80 mmHg. Mean eGFR was 43.4 ؎ 13.5 ml/min per 1.73 m 2 , and median (interquartile range) protein excretion was 0.17 g/24 h (0.07 to 0.81 g/24 h). Lower eGFR was associated with older age, lower socioeconomic and educational level, cigarette smoking, self-reported CVD, peripheral arterial disease, and elevated BP.Conclusions: Lower level of eGFR was associated with a greater burden of CVD as well as lower socioeconomic and educational status. Long-term follow-up of participants will provide critical insights into the epidemiology of CKD and its relationship to adverse outcomes.

Abstract-Distal nephron renin may provide a possible pathway for angiotensin (Ang) I generation from proximally delivered angiotensinogen. To examine the effects of Ang II on distal nephron renin, we compared renin protein and mRNA expression in control and Ang II-infused rats. Kidneys from sham (nϭ9) and Ang II-infused (80 ng/kg per minute, 13 days, nϭ10) Sprague-Dawley rats were processed by immunohistochemistry, Western blot, reverse transcriptase-polymerase chain reaction (RT-PCR), and quantitative real-time RT-PCR. Ang II infusion increased systolic blood pressure (181Ϯ4 versus 115Ϯ5 mm Hg) and suppressed plasma and kidney cortex renin activity. Renin immunoreactivity was suppressed in juxtaglomerular apparatus (JGA) cells in Ang II-infused rats compared with sham (0.1Ϯ0.1 versus 1.0Ϯ0.1 relative ratio) but increased in distal nephron segments (6.4Ϯ1.4 versus 1.0Ϯ0.1 cortex; 2.5Ϯ0.3 versus 1.0Ϯ0.2 medulla). Tubular renin immunostaining was apically distributed in principal cells colocalizing with aquaporin-2 in connecting tubules and cortical and medullary collecting ducts. Renin protein levels were decreased in the kidney cortex of Ang II-infused rats compared with that of sham (0.4Ϯ0.2 versus 1.0Ϯ0.4) rats but higher in the kidney medulla (1.2Ϯ0.4 versus 1.0Ϯ0.1). In kidney medulla, RT-PCR and quantitative real-time PCR showed similar levels of renin transcript in both groups. In summary, the detection of renin mRNA in the renal medulla, which is devoid of JGA, indicates local synthesis rather than an uptake of JGA renin. In contrast to the inhibitory effect of Ang II on JGA renin, Ang II infusion stimulates renin protein expression in collecting ducts and maintains renin transcriptional levels in the medulla, which may contribute to the increased intrarenal Ang II levels in Ang II-dependent hypertension. Key Words: renin Ⅲ angiotensin II Ⅲ angiotensinogen Ⅲ immunohistochemistry Ⅲ Western blot R enin is synthesized primarily by the juxtaglomerular apparatus (JGA). 1 However, renin mRNA and protein have been detected in proximal, connecting tubule and collecting duct cells of human and mouse kidneys as well as in extrarenal tissues. [2][3][4][5][6][7] Although regulation of renin synthesis and secretion from JGA cells has been extensively studied, 1,8 -13 very little is known about the regulation of tubular renin. 7,14 -16 Renin formation in tubular segments may have greater importance than previously thought in view of evidence of high concentrations of angiotensinogen (AGT), as well as angiotensin (Ang) I and Ang II in proximal tubule fluid, 17,18 and in view of the enhancement of renal AGT mRNA and protein levels in Ang II-dependent hypertension. 19,20 Recent studies in Ang II-infused hypertensive rats have shown that there is an increased urinary excretion of AGT, 21 which is closely correlated with intrarenal Ang II content. 21 Enhancement of urinary AGT excretion suggests increased distal nephron AGT delivery and subsequent Ang I and Ang II formation as long as there is availability of an adequate...

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.

Levels of apolipoprotein A1 are decreased and levels of homocysteine, lipoprotein(a), fibrinogen, and C-reactive protein are increased among patients with chronic kidney disease.

Background The purpose of this study is to evaluate serum bicarbonate as a risk factor for renal outcomes, cardiovascular events and mortality in patients with chronic kidney disease (CKD). Study Design Observational cohort study. Setting & Participants 3939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 - December 2008. Predictor Serum bicarbonate. Outcomes Renal outcomes, defined as end-stage renal disease (either initiation of dialysis or kidney transplantation) or 50% reduction in eGFR; atherosclerotic events (myocardial infarction, stroke, peripheral arterial disease); congestive heart failure events; and death. Measurements Time to event. Results The mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m2, and the median serum bicarbonate was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, and 332 experienced an atherosclerotic event and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal endpoint was 3% lower per mEq/L increase in serum bicarbonate (HR, 0.97; 95% CI, 0.94-0.99; p=0.01). The association was stronger for participants with eGFR> 45ml/min/1.73m2 (HR, 0.91; 95%CI, 0.85-0.97; p=0.004). The risk of heart failure increased by 14% (HR, 1.14; 95%CI, 1.03-1.26; p=0.02) per mEq/L increase in serum bicarbonate over 24 mEq/L. Serum bicarbonate was not independently associated with atherosclerotic events (HR, 0.99; 95%CI, 0.95-1.03; p=0.6) and all-cause mortality (HR, 0.98; 95%CI, 0.95-1.02; p=0.3). Limitations Single measurement of sodium bicarbonate. Conclusions In a cohort of participants with CKD, low serum bicarbonate was an independent risk factor for kidney disease progression, particularly for participants with preserved kidney function. The risk of heart failure was higher at the upper extreme of serum bicarbonate. There was no association between serum bicarbonate and all-cause mortality or atherosclerotic events.

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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