Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor β1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat

Erman, Arie; Veksler, Semyon; Gafter, Uzi; Boner, G; Wittenberg, C; Dijk, David Jonathan van

doi:10.3317/jraas.2004.032

Cited by 25 publications

(16 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The small number of SS patients as well as the use of other medications in SR group such as ACEi and prednisone could interfere with the results. As previously reported, the treatment with ACEi reduced plasma TGF-␤ levels in experimental models of proteinuria and diabetic nephropathy (30,31). In addition, steroid administration also decreased renal expression of TGF-␤ in patients with severe proteinuria (15).…”

Section: Discussionsupporting

confidence: 56%

Immune Mediators in Idiopathic Nephrotic Syndrome: Evidence for a Relation Between Interleukin 8 and Proteinuria

et al. 2008

View full text Add to dashboard Cite

ABSTRACT:The pathogenesis of idiopathic nephrotic syndrome (INS) remains unknown. Several findings suggest a role for the immune system. This study aimed to evaluate immune mediators in INS by measuring plasma and urinary levels of transforming growth factor ␤ 1 (TGF-␤ 1 ), monocyte chemoattractant protein-1 (MCP-1/ CCL2), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and IL-8 (IL-8/CXCL8) in pediatric patients with INS and in age-matched healthy controls. Patients were divided according to their response to corticosteroids: steroid-sensitive (SS, n ϭ 8), or steroid-resistant (SR, n ϭ 24). Immune mediators were also compared in regard with disease activity (relapse and remission). Immune mediators were measured by ELISA. Plasma TGF-␤ 1 levels in SR patients were approximately 2.8-fold higher than control values (p Ͻ 0.05). Urinary IL-8/CXCL8 was 2.9-fold higher in INS patients in relapse (proteinuria Ͼ100 mg/m 2 /24 h) when compared with patients in remission (p Ͻ 0.05), and levels had a positive correlation with individual proteinuria values (p Ͻ 0.05). Urinary IL-8/CXCL8 was significantly higher in relapsed SR than in SS patients in remission. No changes in MCP-1/CCL2 and RANTES/CCL5 levels were detected. Our findings suggest that IL-8/CXCL8 and TGF-␤ 1 are involved in the pathogenesis of INS: IL-8/CXCL8 associated with local changes in glomerular permeability and TGF-␤ 1 could be related to worse response to corticosteroids. (Pediatr Res 64: 637-642, 2008)

show abstract

Section: Discussionsupporting

confidence: 56%

Immune Mediators in Idiopathic Nephrotic Syndrome: Evidence for a Relation Between Interleukin 8 and Proteinuria

et al. 2008

View full text Add to dashboard Cite

show abstract

“…In support of this, Ang II has been shown to induce marked glomerular sclerosis 27 with cell proliferation of the glomerular mesangium, 28 vascular endothelium, 29 tubular epithelium 30 and the vascular smooth muscle. 31 Ang II causes podocyte injury by increasing glomerular capillary pressure through a selective constriction of efferent arterioles.…”

Section: Discussionmentioning

confidence: 99%

Renoprotective effects of an angiotensin II receptor blocker in experimental model rats with hypertension and metabolic disorders

et al. 2009

View full text Add to dashboard Cite

Metabolic syndrome (MS) is an independent risk factor for chronic kidney diseases. As the renin-angiotensin system (RAS) is known to have a key role in renal damage, blockade of RAS may show renoprotective effects in MS. In this study, we investigated the renoprotective effects and mechanisms of action of an angiotensin receptor blocker (ARB) in spontaneously hypertensive (SHR/NDmcr-cp) rats as a model of MS. Male SHR/NDmcr-cp rats at 9 weeks of age were divided into three groups, each of which was treated for 12 weeks with vehicle, hydralazine (7.5 mg kg À1 per day, p.o.) or ARB (olmesartan, 5 mg kg À1 per day, p.o.). Blood pressure and urinary protein (UP) excretion were monitored. Kidney tissues were subjected to histological, immunohistochemical and molecular analyses. UP excretion increased with age in vehicle-treated SHR/NDmcr-cp rats compared with that in age-matched WKY/Izm rats. In addition, there was significant glomerular damage (increased glomerular sclerosis index, desmin staining and proliferating cell nuclear antigen (PCNA)-positive cells, electron microscopic findings of podocyte injury) and tubulointerstitial damage (increased tubulointerstitial fibrosis index, type IV collagen staining, PCNA-positive cells and expression of TGF-b mRNA) in vehicle-treated SHR/NDmcr-cp rats compared with that in control rats. All the findings that related to glomerular and tubulointerstitial damage were significantly improved by ARB. Hydralazine mitigated the observed renal damage but was much less effective than ARB, despite similar decreases in blood pressure. There were no significant differences in glucose and lipid metabolism among vehicle-treated, hydralazine-treated and ARB-treated SHR/NDmcr-cp animals. These data suggest that RAS is deeply involved in the pathogenesis of renal damage in MS, and ARBs could provide a powerful renoprotective regimen for patients with MS.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor β1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat

Cited by 25 publications

References 37 publications

Immune Mediators in Idiopathic Nephrotic Syndrome: Evidence for a Relation Between Interleukin 8 and Proteinuria

Immune Mediators in Idiopathic Nephrotic Syndrome: Evidence for a Relation Between Interleukin 8 and Proteinuria

Renoprotective effects of an angiotensin II receptor blocker in experimental model rats with hypertension and metabolic disorders

Stop chronic kidney disease progression: Time is approaching

Contact Info

Product

Resources

About