scholarly journals The Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Advanced-Stage Diabetic Kidney Disease Taking Renin-Angiotensin System Blockers

2020 ◽  
Vol Volume 13 ◽  
pp. 215-225
Author(s):  
Keiji Hirai ◽  
Junki Morino ◽  
Saori Minato ◽  
Shohei Kaneko ◽  
Katsunori Yanai ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Advanced Stage ◽  
Efficacy And Safety ◽  
Angiotensin System ◽  
Diabetic Kidney ◽  
Renin Angiotensin ◽  
Sodium Glucose Cotransporter ◽  
Renin Angiotensin System Blockers

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.

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.

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.

scholarly journals Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade

2015 ◽  
Vol 4 (6) ◽  
pp. 1325-1347 ◽  
Author(s):  
Maria Perez-Gomez ◽  
Maria Sanchez-Niño ◽  
Ana Sanz ◽  
Catalina Martín-Cleary ◽  
Marta Ruiz-Ortega ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Diabetic Kidney ◽  
Renin Angiotensin ◽  
Horizon 2020
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