Urinary Angiotensinogen as a Novel Early Biomarker of Intrarenal Renin^|^ndash;Angiotensin System Activation in Experimental Type 1 Diabetes

Kamiyama, Masumi; Zsombok, Andrea; Kobori, Hiroyuki

doi:10.1254/jphs.12076fp

Cited by 44 publications

(56 citation statements)

References 72 publications

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“…A recent individual patient meta-analysis has challenged early changes in proteinuria as a surrogate end point for kidney disease progression (Inker et al, 2014) is precedent to increased urinary albumin in patients with type 1 diabetes (Saito et al, 2009, Kamiyama et al, 2012. In a study with patients with type 2 diabetes,…”

Section: Discussionmentioning

confidence: 99%

Sex‐dependent differences in renal angiotensinogen as an early marker of diabetic nephropathy

et al. 2015

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Accepted ArticleThis article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an 'Accepted Article', doi: 10.1111/apha.12441 This article is protected by copyright. All rights reserved. Accepted ArticleThis article is protected by copyright. All rights reserved. Running Title:Renal angiotensinogen in diabetic nephropathy Abstract AIM. The renal renin-angiotensin system (RAS) has been implicated in the pathogenesis of diabetic nephropathy. The aim of this study was to investigate sex differences in renal renin-angiotensin system (RAS) and the roles of androgens in diabetes-associated renal injury. METHODS.Renal injury and fibrosis was studied in streptozotocin-induced diabetic Accepted ArticleThis article is protected by copyright. All rights reserved.CONCLUSIONS. These data indicate that renal but not hepatic AOGEN or renin is positively associated with diabetic albuminuria and contribute to the sex-dependent differences in renal injury. Androgens may contribute to albuminuria in male independently of the RAS.

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Section: Discussionmentioning

confidence: 99%

Sex‐dependent differences in renal angiotensinogen as an early marker of diabetic nephropathy

et al. 2015

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“…A key factor in the activation of the intrarenal RAS is stimulation of renal proximal tubular angiotensinogen (AGT), which is the precursor of angiotensin peptides [3]. Elevated intrarenal AGT levels have been observed in animal models of both type-1 and type-2 DM [5][6][7]. Immunohistological analyses demonstrated augmentation of AGT mainly in proximal tubules in the kidneys of DM models.…”

Section: Introductionmentioning

confidence: 99%

Canagliflozin Prevents Intrarenal Angiotensinogen Augmentation and Mitigates Kidney Injury and Hypertension in Mouse Model of Type 2 Diabetes Mellitus

et al. 2019

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Background: Hypertension and renal injury are common complications of type 2 diabetes mellitus (T2DM). Hyperglycemia stimulates renal proximal tubular angiotensinogen (AGT) expression via elevated oxidative stress contributing to the development of high blood pressure and diabetic nephropathy. The sodium glucose cotransporter 2 (SGLT2) in proximal tubules is responsible for the majority of glucose reabsorption by renal tubules. We tested the hypothesis that SGLT2 inhibition with canagliflozin (CANA) prevents intrarenal AGT augmentation and ameliorates kidney injury and hypertension in T2DM. Methods: We induced T2DM in New Zealand obese mice with a high fat diet (DM, 30% fat) with control mice receiving regular fat diet (ND, 4% fat). When DM mice exhibited > 350 mg/dL blood glucose levels, both DM- and ND-fed mice were treated with 10 mg/kg/day CANA or vehicle by oral gavage for 6 weeks. We evaluated intrarenal AGT, blood pressure, and the development of kidney injury. Results: Systolic blood pressure in DM mice (133.9 ± 2.0 mm Hg) was normalized by CANA (113.9 ± 4.0 mm Hg). CANA treatment ameliorated hyperglycemia-associated augmentation of renal AGT mRNA (148 ± 21 copies/ng RNA in DM, and 90 ± 16 copies/ng RNA in DM + CANA) and protein levels as well as elevation of urinary 8-isoprostane levels. Tubular fibrosis in DM mice (3.4 ± 0.9-fold, fibrotic score, ratio to ND) was suppressed by CANA (0.9 ± 0.3-fold). Furthermore, CANA attenuated DM associated increased macrophage infiltration and cell proliferation in kidneys of DM mice. Conclusions: CANA prevents intrarenal AGT upregulation and oxidative stress and which may mitigate high blood pressure, renal tubular fibrosis, and renal inflammation in T2DM.

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“…20 The UAGT level was used to asses local RAS activity in the kidneys in research on such primary diseases as HT, diabetic nephropathy, chronic kidney disease and IgA nephropathy. [21][22][23][24][25] In a study on kidney transplantation, the UAGT/Ucre ratio in patients with HT was higher than in normotensive patients, and the difference was associated with proteinuria. 26 In patients with IgA nephropathy, the UAGT level was shown to be correlated with AGT gene expression in renal tissues and angiotensin-II immunoreactivity.…”

Section: Discussionmentioning

confidence: 99%

Relationship between blood pressure variability and renal activity of the renin–angiotensin system

et al. 2015

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Local renin-angiotensin system (RAS) activity in the kidneys is a pathogenetic factor in patients with primary hypertension. This study aimed to determine the relationship between local kidney RAS activity and blood pressure variability, as the literature currently lacks any such study. The study included 73 consecutive primary hypertensive patients. All patients underwent 24-h ambulatory blood pressure monitoring to determine the average real variability (ARV) index, as an indicator of blood pressure variability. Local RAS activity was determined using the urine angiotensinogen/creatinine (UAGT/UCre) ratio. The high UAGT/UCre ratio group had significantly higher mean 24-h systolic ARV than the low UAGT/UCre ratio group (13.2±3.4 vs 11.0±2.6, P=0.003). Similarly, the high UAGT/UCre ratio group had significantly higher mean 24-h diastolic ARV than the low UAGT/UCre ratio group (10.8±3.2 vs 8.7±2.2, P=0.001). Multivariate regression analysis showed that Log(UAGT/UCre) was an independent predictor of both 24-h diastolic ARV and 24-h systolic ARV. Local RAS activity in the kidneys might have a role in blood pressure variability. On the basis of these findings, we think that additional prospective studies are needed to more fully discern the effect of local RAS activity on blood pressure variability.

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Urinary Angiotensinogen as a Novel Early Biomarker of Intrarenal Renin^|^ndash;Angiotensin System Activation in Experimental Type 1 Diabetes

Cited by 44 publications

References 72 publications

Sex‐dependent differences in renal angiotensinogen as an early marker of diabetic nephropathy

Sex‐dependent differences in renal angiotensinogen as an early marker of diabetic nephropathy

Canagliflozin Prevents Intrarenal Angiotensinogen Augmentation and Mitigates Kidney Injury and Hypertension in Mouse Model of Type 2 Diabetes Mellitus

Relationship between blood pressure variability and renal activity of the renin–angiotensin system

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