scholarly journals Present and Future in the Treatment of Diabetic Kidney Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Borja Quiroga ◽  
David Arroyo ◽  
Gabriel de Arriba
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Diabetic Kidney ◽  
Renin Angiotensin ◽  
Renin Inhibitors

Diabetic kidney disease is the leading cause of end-stage renal disease. Albuminuria is recognized as the most important prognostic factor for chronic kidney disease progression. For this reason, blockade of renin-angiotensin system remains the main recommended strategy, with either angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. However, other antiproteinuric treatments have begun to be studied, such as direct renin inhibitors or aldosterone blockers. Beyond antiproteinuric treatments, other drugs such as pentoxifylline or bardoxolone have yielded conflicting results. Finally, alternative pathogenic pathways are being explored, and emerging therapies including antifibrotic agents, endothelin receptor antagonists, or transcription factors show promising results. The aim of this review is to explain the advances in newer agents to treat diabetic kidney disease, along with the background of the renin-angiotensin system blockade.

scholarly journals MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
José María Mora-Gutiérrez ◽  
José Antonio Rodríguez ◽  
María A. Fernández-Seara ◽  
Josune Orbe ◽  
Francisco Javier Escalada ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Early Stage ◽  
Renin Angiotensin System ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Angiotensin System ◽  
Diabetic Kidney ◽  
Renin Angiotensin

AbstractMatrix metalloproteinases have been implicated in diabetic microvascular complications. However, little is known about the pathophysiological links between MMP-10 and the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). We tested the hypothesis that MMP-10 may be up-regulated in early stage DKD, and could be down-regulated by angiotensin II receptor blockade (telmisartan). Serum MMP-10 and TIMP-1 levels were measured in 268 type 2 diabetic subjects and 111 controls. Furthermore, histological and molecular analyses were performed to evaluate the renal expression of Mmp10 and Timp1 in a murine model of early type 2 DKD (db/db) after telmisartan treatment. MMP-10 (473 ± 274 pg/ml vs. 332 ± 151; p = 0.02) and TIMP-1 (573 ± 296 ng/ml vs. 375 ± 317; p < 0.001) levels were significantly increased in diabetic patients as compared to controls. An early increase in MMP-10 and TIMP-1 was observed and a further progressive elevation was found as DKD progressed to end-stage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and significant albuminuria compared to wild-type, which was prevented by telmisartan. MMP-10 and TIMP-1 are increased from the early stages of type 2 diabetes. Prevention of MMP-10 upregulation observed in diabetic mice could be another protective mechanism of RAS blockade in DKD.

The Potential Therapeutic Value of Renin-Angiotensin System Inhibitors in the Treatment of Colorectal Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Ehsan Tabatabai ◽  
Majid Khazaei ◽  
Mohammad Reza Parizadeh ◽  
Mohammad Nouri ◽  
Seyed Mahdi Hassanian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Promote Cell Proliferation

: Colorectal cancer is the third most common cancer globally. Despite extensive preclinical and clinical studies, it is still among the leading causes of cancer-related death, and a need for new therapeutic options is required. The renin-angiotensin system plays an important role in regulating blood pressure and cell growth. In addition to their hemodynamic effects, some of the renin-angiotensin system components, such as angiotensin, are also growth factors that promote cell proliferation and angiogenesis, and its dysregulation is reported to be associated with poor prognosis in colorectal cancer. Here we describe the critical role of the renin-angiotensin system pathway in colorectal cancer as well as the preclinical and clinical investigations renin-angiotensin system inhibitors: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers as a potential therapeutic target in the treatment of colorectal cancer. Several studies have been shown that the inhibition of these pathways can reduce tumor growth and metastasis; however, some of the data remain inconsistent. There is accumulating evidence of the therapeutic potential of some inhibitors, such as Losartan which are now in clinical phases in the treatment of several malignancies using Nivolumab in combination with FOLFIRINOX in pancreatic cancer. Further investigations are warranted to improve the efficacy and selectivity of current and future anticancer strategies targeting renin-angiotensin systems.

Diabetic Kidney Disease: A Renin-Angiotensin-Aldosterone System Focused Review

2009 ◽  
Vol 22 (6) ◽  
pp. 560-570 ◽  
Author(s):  
Pamela F. Hite ◽  
Heather F. DeBellis
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Angiotensin Receptor Blockers ◽  
The United States ◽  
Diabetic Patients ◽  
Converting Enzyme Inhibitors ◽  
Renin Angiotensin Aldosterone System ◽  
Diabetic Kidney ◽  
Renin Angiotensin ◽  
Renin Inhibitors

Diabetic nephropathy, also referred to as diabetic kidney disease, is a multifaceted complication of one of the largest epidemics in the United States. Diabetic patients currently represent approximately 8% of the US population. Aggressive screening and control of diabetes, hypertension, and dyslipidemia as well as dietary protein restriction are vital to the prevention and management of diabetic kidney disease. Because there are no direct pharmacologic options for diabetic kidney disease, treatment is focused on controlling comorbidities that exacerbate the development and progression of diabetic kidney disease. This article will provide an overview of structural renal alterations during the progression of diabetic kidney disease as well as a concise review of current diabetic kidney disease management guidelines with a focus on agents that affect the renin-angiotensin-aldosterone system. At this point in time, the mainstays of therapy are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. More research is currently needed to determine if renin inhibitors will have an active role in the management of diabetic kidney disease.

Renin-angiotensin system within the diabetic podocyte

2015 ◽  
Vol 308 (1) ◽  
pp. F1-F10 ◽  
Author(s):  
Eva Márquez ◽  
Marta Riera ◽  
Julio Pascual ◽  
María José Soler
Keyword(s):  
Angiotensin Ii ◽  
Kidney Disease ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Diabetic Kidney ◽  
Renin Angiotensin ◽  
Filtration Barrier

Diabetic kidney disease is the leading cause of end-stage renal disease. Podocytes are differentiated cells necessary for the development and maintenance of the glomerular basement membrane and the capillary tufts, as well as the function of the glomerular filtration barrier. The epithelial glomerular cells express a local renin-angiotensin system (RAS) that varies in different pathological situations such as hyperglycemia or mechanical stress. RAS components have been shown to be altered in diabetic podocytopathy, and their modulation may modify diabetic nephropathy progression. Podocytes are a direct target for angiotensin II-mediated injury by altered expression and distribution of podocyte proteins. Furthermore, angiotensin II promotes podocyte injury indirectly by inducing cellular hypertrophy, increased apoptosis, and changes in the anionic charge of the glomerular basement membrane, among other effects. RAS blockade has been shown to decrease the level of proteinuria and delay the progression of chronic kidney disease. This review summarizes the local intraglomerular RAS and its imbalance in diabetic podocytopathy. A better understanding of the intrapodocyte RAS might provide a new approach for diabetic kidney disease treatment.

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