Relationship Between Urinary Angiotensinogen and Salt Sensitivity of Blood Pressure in Patients With IgA Nephropathy

Konishi, Yoshio; Nishiyama, Akira; Morikawa, Takashi; Kitabayashi, Chizuko; Shibata, Masa‐Aki; Hamada, Masahiro; Kishida, Masatsugu; Hitomi, Hirofumi; Kiyomoto, Hideyasu; Miyashita, Takenori; Mori, Nozomu; Urushihara, Maki; Kobori, Hiroyuki; Imanishi, Masahito

doi:10.1161/hypertensionaha.110.166843

Cited by 39 publications

(42 citation statements)

References 39 publications

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“…16,17 AGT excretion, which mirrors intrarenal AngII during oxidative stress, is increased by salt in patients with CKD. 27 Remarkably, almost all of the necessary substrates and enzymes for the local generation of AngII, exception for renin, and the receptors on which it acts, were upregulated in the kidneys of 5/6Nx rats fed a high-salt diet. The increased intrarenal AngII with salt in 5/6Nx rat kidneys likely originates in large part from increased proximal tubular AGT and ACE.…”

Section: Discussionmentioning

confidence: 98%

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A Salt-Induced Reno-Cerebral Reflex Activates Renin-Angiotensin Systems and Promotes CKD Progression

Cao

Wang

et al. 2015

Journal of the American Society of Nephrology

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Salt intake promotes progression of CKD by uncertain mechanisms. We hypothesized that a salt-induced reno-cerebral reflex activates a renin-angiotensin axis to promote CKD. Sham-operated and 5/6-nephrectomized rats received a normal-salt (0.4%), low-salt (0.02%), or high-salt (4%) diet for 2 weeks. High salt in 5/6-nephrectomized rats increased renal NADPH oxidase, inflammation, BP, and albuminuria. Furthermore, high salt activated the intrarenal and cerebral, but not the systemic, renin-angiotensin axes and increased the activity of renal sympathetic nerves and neurons in the forebrain of these rats. Renal fibrosis was increased 2.2-fold by high versus low salt, but intracerebroventricular tempol, losartan, or clonidine reduced this fibrosis by 65%, 69%, or 59%, respectively, and renal denervation or deafferentation reduced this fibrosis by 43% or 38%, respectively (all P,0.05). Salt-induced fibrosis persisted after normalization of BP with hydralazine. These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral reflex that is activated by salt and promotes oxidative stress, fibrosis, and progression of CKD independent of BP.

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Section: Discussionmentioning

confidence: 98%

“…27 Renal AGT may be rate limiting for angiotensin II (AngII) generation. 26 Most organs possess a local RAS that is regulated independently and is somewhat compartmentalized from the circulation.…”

mentioning

confidence: 99%

A Salt-Induced Reno-Cerebral Reflex Activates Renin-Angiotensin Systems and Promotes CKD Progression

Cao

Wang

et al. 2015

Journal of the American Society of Nephrology

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“…[13][14][15] The available evidence detailing the effects of sodium restriction in CKD patients is of poor quality, lacks randomization, [16][17][18] a control group, 17 or blinding, 10,11 or does not use gold-standard measurement techniques (e.g., using clinic instead of ambulatory BP). 10,11 Furthermore, several studies failed to either evaluate or adjust for the influence of key confounding factors, such as potassium intake or body weight, 10,11,[19][20][21][22] thereby making it difficult to assess whether the observed results can be solely attributed to dietary sodium.…”

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confidence: 99%

A Randomized Trial of Dietary Sodium Restriction in CKD

McMahon

Bauer

Hawley

et al. 2013

Journal of the American Society of Nephrology

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There is a paucity of quality evidence regarding the effects of sodium restriction in patients with CKD, particularly in patients with pre-end stage CKD, where controlling modifiable risk factors may be especially important for delaying CKD progression and cardiovascular events. We conducted a doubleblind placebo-controlled randomized crossover trial assessing the effects of high versus low sodium intake on ambulatory BP, 24-hour protein and albumin excretion, fluid status (body composition monitor), renin and aldosterone levels, and arterial stiffness (pulse wave velocity and augmentation index) in 20 adult patients with hypertensive stage 3-4 CKD as phase 1 of the LowSALT CKD study. Overall, salt restriction resulted in statistically significant and clinically important reductions in BP (mean reduction of systolic/diastolic BP, 10/4 mm Hg; 95% confidence interval, 5 to 15 /1 to 6 mm Hg), extracellular fluid volume, albuminuria, and proteinuria in patients with moderate-to-severe CKD. The magnitude of change was more pronounced than the magnitude reported in patients without CKD, suggesting that patients with CKD are particularly salt sensitive. Although studies with longer intervention times and larger sample sizes are needed to confirm these benefits, this study indicates that sodium restriction should be emphasized in the management of patients with CKD as a means to reduce cardiovascular risk and risk for CKD progression.

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“…Although the mechanism of renal dysfunction in IUGR offspring has not been completely clarified, substantial evidence indicates that the renin-angiotensin system (RAS) may be a possible pathway (15). In many other diseases including obstructive nephropathy (9), diabetic nephropathy (15), membranous nephropathy, chronic glomerulonephritis, and IgA nephritis (11,12), the activation of the intrarenal RAS plays important role in kidney dysfunction. In IUGR, there exists an immature function of RAS (14), which may result in inappropriate activation of RAS.…”

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confidence: 99%

“…Although the first generation of infants from the "surfactant era" who may have chronic kidney disease pathogenesis are now reaching young adulthood, no reliable screening methods or followup procedures to monitor these dominant diseases have been established to date (8). Recently, urinary angiotensinogen (AGT) was proposed as a novel biomarker to detect kidney dysfunction caused by renal diseases, such as obstructive nephropathy (9), diabetic nephropathy (10,11), membranous nephropathy, chronic glomerulonephritis, and immunoglobulin A nephritis (12,13). However, few studies have focused on urinary AGT in patients born as low-birth-weight infants, and a literature search retrieved no related studies using animal models.…”

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confidence: 99%

Evaluation of kidney dysfunction and angiotensinogen as an early novel biomarker of intrauterine growth restricted offspring rats

et al. 2015

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Background: Few studies have addressed the growing concerns of chronic kidney diseases in children with intrauterine growth restriction (IUGR). Therefore, the purpose of this study was to evaluate long-term kidney dysfunction and determine if urinary angiotensinogen (AGT) was suitable as a novel early biomarker for kidney dysfunction in IUGR offspring. Methods: Pregnant rats underwent bilateral uterine artery ligation, and as a control group, sham surgeries were performed. results: The birth weight was reduced, the urinary AGT to creatinine ratio was significantly higher at week 20, and urinary protein levels were significantly higher at week 32 in IUGR rats than in control rats. On the other hand, the histological findings at week 32 revealed long-term kidney dysfunction, more severe glomerulosclerosis, and greater glomerular diameters in IUGR rats. Moreover, AGT mRNA expression and immunohistological staining were significantly increased in IUGR rats; this suggests that the intrarenal renin-angiotensin system (RAS) contributes to renal dysfunction of IUGR offspring. conclusion: Urinary AGT elevation prior to urinary protein levels suggests that AGT is an early biomarker. At week 32, kidney dysfunction was severe in IUGR rats and intrarenal RAS appeared to be one of the causes. (1) first proposed that many adult diseases may have origins in fetal life, subsequent studies have clarified the associations between intrauterine growth restriction (IUGR) and obesity, hypertension, insulin resistance, and coronary artery disease. Luyckx and Brenner (2) applied these findings to the development of chronic kidney disease and following studies were conducted in animal models as well as human subjects. In these animal studies, IUGR was typically found to be induced by maternal food restriction (3-5); however, no applications to current IUGR rates in developed countries were made; malnutrition during pregnancy due to food restriction during pregnancy is no longer the main cause of IUGR in developed countries.Most cases of IUGR reportedly result from decreased placenta blood flow (6). A decrease in placenta blood flow by maternal bilateral uterine artery ligation was shown in an animal model; however, relatively few studies have been conducted to evaluate subsequent kidney dysfunction. To the best of our knowledge, no previous study has assessed the long-term effects of IUGR on kidney function. Therefore, in this study, we examined kidney dysfunction in a rat model of IUGR induced by bilateral uterine artery ligation for 32 wk after birth.On conducting this study, we also decided to identify clues to detect dormant chronic kidney disease in adults who were born with a low birth weight. Owing to developments in the field of neonatology, the survival rate of infants with a low birth weight has continued to increase (7). Although the first generation of infants from the "surfactant era" who may have chronic kidney disease pathogenesis are now reaching young adulthood, no reliable screening methods or followup procedures to mon...

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Relationship Between Urinary Angiotensinogen and Salt Sensitivity of Blood Pressure in Patients With IgA Nephropathy

Cited by 39 publications

References 39 publications

A Salt-Induced Reno-Cerebral Reflex Activates Renin-Angiotensin Systems and Promotes CKD Progression

A Salt-Induced Reno-Cerebral Reflex Activates Renin-Angiotensin Systems and Promotes CKD Progression

A Randomized Trial of Dietary Sodium Restriction in CKD

Evaluation of kidney dysfunction and angiotensinogen as an early novel biomarker of intrauterine growth restricted offspring rats

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