Enhanced intrarenal oxidative stress and angiotensinogen in IgA nephropathy patients

Kobori, Hiroyuki; Katsurada, Akemi; Ozawa, Yuri; Satou, Ryousuke; Miyata, Kayoko; Hase, Naoki; Suzaki, Yuki; Tanaka, Shōji

doi:10.1016/j.bbrc.2007.04.105

Cited by 74 publications

(106 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23 In these nephrotic mice, renal AII was increased, although renal renin was suppressed, indicating that a fraction of the Agt that is leaked into Bowman's space is converted to AII and that renal AII content is determined by the intactness of glomerular sieving function to restrict filtration of circulating Agt. Our observations with podocyte disruption echo the earlier findings in patients with glomerular 30 although we found that the origin of Agt is the liver and not the kidney itself. Because renin is also reabsorbed by proximal tubule cells through megalin and ACE is expressed on proximal tubule cells, 23 it is likely that AII is generated within the vicinity where Agt protein is accumulated.…”

Section: Discussionsupporting

confidence: 90%

Liver Angiotensinogen Is the Primary Source of Renal Angiotensin II

Matsusaka

Niimura

Shimizu

et al. 2012

Journal of the American Society of Nephrology

Self Cite

237

296

View full text Add to dashboard Cite

Angiotensin II content in the kidney is much higher than in the plasma, and it increases more in kidney diseases through an uncertain mechanism. Because the kidney abundantly expresses angiotensinogen mRNA, transcriptional dysregulation of angiotensinogen within the kidney is one potential cause of increased renal angiotensin II in the setting of disease. Here, we observed that kidney-specific angiotensinogen knockout mice had levels of renal angiotensinogen protein and angiotensin II that were similar to those levels of control mice. In contrast, liver-specific knockout of angiotensinogen nearly abolished plasma and renal angiotensinogen protein and renal tissue angiotensin II. Immunohistochemical analysis in mosaic proximal tubules of megalin knockout mice revealed that angiotensinogen protein was incorporated selectively in megalin-intact cells of the proximal tubule, indicating that the proximal tubule reabsorbs filtered angiotensinogen through megalin. Disruption of the filtration barrier in a transgenic mouse model of podocyte-selective injury increased renal angiotensin II content and markedly increased both tubular and urinary angiotensinogen protein without an increase in renal renin activity, supporting the dependency of renal angiotensin II generation on filtered angiotensinogen. Taken together, these data suggest that liverderived angiotensinogen is the primary source of renal angiotensinogen protein and angiotensin II. Furthermore, an abnormal increase in the permeability of the glomerular capillary wall to angiotensinogen, which characterizes proteinuric kidney diseases, enhances the synthesis of renal angiotensin II. CKDs are often progressive and involve cardiovascular diseases. Pharmacological intervention of angiotensin II (AII) is the only currently available therapeutic clinical measure with proven effectiveness in protecting the kidney from progressive loss of renal function in CKD. However, in these conditions, circulating AII is typically not elevated. Of note, AII content in renal tissues is markedly higher than content in the circulation, and it is regulated in a manner distinct from circulating AII. 1-3 These findings have formed the currently prevailing notion that the kidney in and of itself is furnished with a full set of components necessary for de novo AII synthesis. In support of this notion, studies have shown that renal AII is elevated in hypertension and

show abstract

Section: Discussionsupporting

confidence: 90%

Liver Angiotensinogen Is the Primary Source of Renal Angiotensin II

Matsusaka

Niimura

Shimizu

et al. 2012

Journal of the American Society of Nephrology

Self Cite

237

296

View full text Add to dashboard Cite

show abstract

“…As described previously, we reported that intrarenal AGT immunoreactivity is significantly correlated positively with urinary occult blood, UPro/UCre, and serum creatinine, and correlated negatively with creatinine clearance in IgA nephropathy patients. 24 We do not have any data regarding urinary occult blood or intrarenal AGT immunoreactivity in this study; however, these similar correlation patterns may suggest that urinary AGT levels reflect intrarenal AGT protein levels. In general, the increases in UAlb/UCre, UPro/UCre, and serum creatinine, and the decrease in eGFR represent severity or aggravated renal function in CKD.…”

Section: Single Regression Analysesmentioning

confidence: 57%

“…19-23 We also recently reported that intrarenal AGT immunoreactivity is enhanced in IgA nephropathy patients. 24 Moreover, intrarenal AGT immunoreactivity is significantly correlated positively with urinary occult blood, urinary protein-creatinine ratio (UPro/UCre), and serum creatinine, and correlated negatively with creatinine clearance. 24 Recently, we provided evidence demonstrating that urinary AGT levels reflect intrarenal Ang II activity associated with increased risk for deterioration of renal function in CKD patients.…”

Section: Introductionmentioning

confidence: 98%

Urinary angiotensinogen as a potential biomarker of severity of chronic kidney diseases

Kobori

Ohashi

Katsurada

et al. 2008

Journal of the American Society of Hypertension

Self Cite

134

132

View full text Add to dashboard Cite

We previously reported that urinary excretion rates of angiotensinogen (AGT) provide a specific index of the activity of the intrarenal renin-angiotensin system in angiotensin II-dependent hypertensive rats. Meanwhile, we have recently developed direct enzyme-linked immunosorbent assays (ELISAs) to measure plasma and urinary AGT in humans. This study was performed to test a hypothesis that urinary AGT levels are enhanced in chronic kidney disease (CKD) patients and correlated with some clinical parameters. Eighty patients with CKD (37 women and 43 men, from 18 to 94 years old) and seven healthy volunteers (two women and five men, from 27 to 43 years old) were included. Plasma AGT levels showed a normal distribution; however, urinary AGT-creatinine ratios (UAGT/UCre) deviated from the normal distribution. When a logarithmic transformation was executed, Log(UAGT/UCre) levels showed a normal distribution. Therefore, Log(UAGT/UCre) levels were used for further analyses. Log(UAGT/UCre) levels were not correlated with age, gender, height, body weight, body mass index, systolic blood pressure, diastolic blood pressure, serum sodium levels, serum potassium levels, urinary sodium-creatinine ratios, plasma renin activity, or plasma AGT levels. However, Log(UAGT/UCre) levels were significantly correlated positively with urinary albumin-creatinine ratios, fractional excretion of sodium, urinary protein-creatinine ratios, and serum creatinine, and correlated negatively with estimated glomerular filtration rate. Log(UAGT/ UCre) levels were significantly increased in CKD patients compared with control subjects (1.8801 ± 0.0885 vs. 0.9417 ± 0.1048; P = .0024). These data confirmed our earlier report and showed that a new ELISA assay is a valid approach for measuring urinary AGT.

show abstract

“…[20][21][22][23] Many experimental and clinical studies in chronic kidney disease models described possible mechanisms for development of proteinuria via the local RAS in kidney. 9,10,20 Previous studies evaluating the pathogenesis of proteinuria in preeclampsia have demonstrated pathogenic mechanisms including down-regulation of podocyte expression of nephrin, increased endothelin and decreased vascular endothelial growth factor (VEGF), indicating a mechanism where the endothelium loses its fenestrations, an alteration which contributes to protein loss in the urine. [29][30][31][32] Likewise, experimental models demonstrated that locally produced ANG II in the kidney may induce proteinuria via reduction of nephrin expression and podocyte injury and stimulated expression of some cytokines such as VEGF.…”

Section: Discussionmentioning

confidence: 99%

“…8 Similarly, urinary AGT was significantly correlated with intrarenal AGT gene expression and ANG II immunoreactivity in patients with normotensive IgA nephropathy. 9 Recent evidence has also revealed that inappropriate activation of intrarenal RAS is an important contributor to the pathogenesis of hypertension and renal injury. [10][11][12] We hypothesized that local RAS activation in the kidneys may have a role in the pathophysiological mechanisms for development of preeclampsia.…”

Section: Introductionmentioning

confidence: 99%

Association between urinary angiotensinogen, hypertension and proteinuria in pregnant women with preeclampsia

Yılmaz

Yıldırım

Yılmaz

et al. 2014

J Renin Angiotensin Aldosterone Syst

View full text Add to dashboard Cite

Introduction: Preeclampsia is a life-threatening disorder of pregnancy. The pathogenic mechanisms of preeclampsia remain uncertain. The aim of this study is to investigate the relation between urinary angiotensinogen (UAGT) levels, an indicator of local renin-angiotensin system (RAS) activity in the kidney, and blood pressure and urinary protein excretion in preeclampsia. Materials and methods: For this study, 90 women aged between 20-39 years were recruited. Spot urine samples were collected to measure urinary angiotensinogen/creatinine ratio (UAGT/UCre). Log(UAGT/UCre) was compared in pregnancies with and without preeclampsia and non-pregnant controls. Factors affecting log(UAGT/UCre) in pregnancies were also investigated. Results: In all pregnancies log(UAGT/UCre) levels were significantly higher than in non-pregnant controls (0.58±0.19 vs. 0.33±0.14, respectively, p=0.002). However, log(UAGT/UCre) levels in pregnancies with preeclampsia were slightly lower than in normal pregnancies (0.52±0.18 vs. 0.64±0.19, respectively, p=0.012). Log(UAGT/UCre) levels were correlated positively with blood pressure and proteinuria in pregnancies with preeclampsia. However, log(UAGT/UCre) levels were not correlated with age, height, body weight, gestational age, body mass index, and serum creatinine. Conclusion: This study showed that elevated local RAS activity in kidney was correlated with high blood pressure and proteinuria in preeclampsia. Local RAS activation in the kidneys may be one of the contributing factors in the development of preeclampsia.

show abstract

Enhanced intrarenal oxidative stress and angiotensinogen in IgA nephropathy patients

Cited by 74 publications

References 54 publications

Liver Angiotensinogen Is the Primary Source of Renal Angiotensin II

Liver Angiotensinogen Is the Primary Source of Renal Angiotensin II

Urinary angiotensinogen as a potential biomarker of severity of chronic kidney diseases

Association between urinary angiotensinogen, hypertension and proteinuria in pregnant women with preeclampsia

Contact Info

Product

Resources

About