Systemic and local effects of angiotensin II blockade in experimental diabetic nephropathy

Yıldırım

J Renin Angiotensin Aldosterone Syst

et al. 2014

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.

Section: Discussionmentioning

confidence: 99%

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

Yıldırım

J Renin Angiotensin Aldosterone Syst

et al. 2014

“…The inhibition of PKC (a downstream mediator of Ang II which enhances the dose of both VEGF and TGF-β) by ruboxistaurin reduced both VEGF and TGF-β expression, ameliorating albuminuria and glomerulosclerosis [36]. Ang II not only upregulates VEGF and TGF-β expression, it also upregulates platelet-derived growth factor and tumour necrosis factor, growth factors also associated with diabetic nephropathy and proteinuria [37]. Irbesartan, an Ang II antagonist, blocked the increase in expression of all of these growth factors in glomeruli of uninephrectomised, streptozotocin-induced diabetic rats [37].…”

Section: Vegf Regulation In Glomerulopathologiesmentioning

confidence: 99%

The Importance of Cellular VEGF Bioactivity in the Development of Glomerular Disease

Foster

2009

Nephron Exp Nephrol

The bioactivity of glomerular VEGF (or activity of available VEGF) is critical to the physiological maintenance of the glomerular filtration barrier. Disturbances in glomerular VEGF expression have been linked to numerous glomerulopathies, highlighting its importance in disease progression within the kidney. However, the changes in expression are not consistent between conditions; enhanced expression sometimes appears to have a renoprotective effect, yet at other times it appears destructive. Also, the level of expression can change with the progression of disease. This review focuses on how other cellular factors, such as TGF-β and nitric oxide, work in concert to affect the bioactivity, which is not necessarily the same as the expression of VEGF, in different glomerulopathies and attempts to explain some of the paradoxes between glomerulopathies. In conclusion, the bioactivity of glomerular VEGF is regulated by many factors that are themselves moderated by changes in the local glomerular environment, such as mechanical strain and hyperglycaemia. Thus, to understand VEGF signalling in glomerular disease progression, we must examine it in the context of other appropriate cellular factors.

“…RAS blockers have a significant impact on the rate of decline of GFR in CKD patients with proteinuria [70][71][72] . They exert their action through many mechanisms including their hemodynamic effect on glomerular tuft pressure [73,74] , inhibition of cytokine overproduction [75][76][77][78][79] , increased serum and tissue angiotensin 1-7 [80][81][82] and stimulation of Klotho gene expression in CKD patients. The RAS-mediated renal damage might be through Klotho gene manipulation [54] .…”

Section: Pathogenesismentioning

confidence: 99%

Stop chronic kidney disease progression: Time is approaching

Din¹,

Salem²,

Abdulazim³

2016

WJN

Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the antisenescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression.