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.

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.

scholarly journals Sodium-glucose cotransporter 2 inhibition: towards an indication to treat diabetic kidney disease

2020 ◽  
Vol 35 (Supplement_1) ◽  
pp. i13-i23 ◽  
Author(s):  
Jose Luis Górriz ◽  
Juan F Navarro-González ◽  
Alberto Ortiz ◽  
Ander Vergara ◽  
Julio Nuñez ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Safety Management ◽  
Blood Glucose Control ◽  
European Medicines Agency ◽  
Diabetic Patients ◽  
Diabetic Kidney ◽  
Renin Angiotensin ◽  
Sodium Glucose Cotransporter

Abstract Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have clearly demonstrated their beneficial effect in diabetic kidney disease (DKD) on top of the standard of care [blood glucose control, renin–angiotensin system blockade, smoking cessation and blood pressure (BP) control], even in patients with overt DKD. However, the indication of this drug class is still blood glucose lowering in type 2 diabetic patients with estimated glomerular filtration rate &gt;45 mL/min/1.73 m2. Based on the new evidence, several scientific societies have emphasized the preferential prescription of SGLT2i for patients at risk of heart failure or kidney disease, but still within the limits set by health authorities. A rapid positioning of both the European Medicines Agency and the US Food and Drug Administration will allow patients with overt DKD to benefit from SGLT2i. Clinical experience suggests that SGLT2i safety management may in part mirror renin–angiotensin blockade safety management in patients with overt DKD. This review focuses on the rationale for an indication of SGTL2i in DKD. We further propose clinical steps for maximizing the safety of SGLT2i in DKD patients on other antidiabetic, BP or diuretic medication.

Potential of Renin-Angiotensin-Aldosterone System Modulations in Diabetic Kidney Disease: Old Players to New Hope!

2020 ◽  
Author(s):  
Vajir Malek ◽  
Sachin V. Suryavanshi ◽  
Nisha Sharma ◽  
Yogesh A. Kulkarni ◽  
Shrikant R. Mulay ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin Aldosterone System ◽  
Diabetic Kidney ◽  
Renin Angiotensin

scholarly journals Antihypertensive Treatment in Diabetic Kidney Disease: The Need for a Patient-Centered Approach

Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 382
Author(s):  
Bonino ◽  
Leoncini ◽  
De Cosmo ◽  
Greco ◽  
Russo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Blood Pressure Reduction ◽  
Pressure Control ◽  
Renal Outcome ◽  
Diabetic Patients ◽  
Pressure Reduction ◽  
Diabetic Kidney ◽  
Renin Angiotensin

Diabetic kidney disease affects up to forty percent of patients with diabetes during their lifespan. Prevention and treatment of diabetic kidney disease is currently based on optimal glucose and blood pressure control. Renin–angiotensin aldosterone inhibitors are considered the mainstay treatment for hypertension in diabetic patients, especially in the presence of albuminuria. Whether strict blood pressure reduction entails a favorable renal outcome also in non-albuminuric patients is at present unclear. Results of several clinical trials suggest that an overly aggressive blood pressure reduction, especially in the context of profound pharmacologic inhibition of the renin–angiotensin–aldosterone system may result in a paradoxical worsening of renal function. On the basis of this evidence, it is proposed that blood pressure reduction should be tailored in each individual patient according to renal phenotype.

scholarly journals Progression of diabetic kidney disease in T2DN rats

2019 ◽  
Vol 317 (6) ◽  
pp. F1450-F1461 ◽  
Author(s):  
Oleg Palygin ◽  
Denisha Spires ◽  
Vladislav Levchenko ◽  
Ruslan Bohovyk ◽  
Mykhailo Fedoriuk ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Disease Progression ◽  
Renal Damage ◽  
Diabetic Kidney Disease ◽  
Weight Ratio ◽  
Renin Angiotensin Aldosterone System ◽  
Diabetic Kidney ◽  
Renin Angiotensin ◽  
Glomerular Damage

Diabetic kidney disease (DKD) is one of the leading pathological causes of decreased renal function and progression to end-stage kidney failure. To explore and characterize age-related changes in DKD and associated glomerular damage, we used a rat model of type 2 diabetic nephropathy (T2DN) at 12 wk and older than 48 wk. We compared their disease progression with control nondiabetic Wistar and diabetic Goto-Kakizaki (GK) rats. During the early stages of DKD, T2DN and GK animals revealed significant increases in blood glucose and kidney-to-body weight ratio. Both diabetic groups had significantly altered renin-angiotensin-aldosterone system function. Thereafter, during the later stages of disease progression, T2DN rats demonstrated a remarkable increase in renal damage compared with GK and Wistar rats, as indicated by renal hypertrophy, polyuria accompanied by a decrease in urine osmolarity, high cholesterol, a significant prevalence of medullary protein casts, and severe forms of glomerular injury. Urinary nephrin shedding indicated loss of the glomerular slit diaphragm, which also correlates with the dramatic elevation in albuminuria and loss of podocin staining in aged T2DN rats. Furthermore, we used scanning ion microscopy topographical analyses to detect and quantify the pathological remodeling in podocyte foot projections of isolated glomeruli from T2DN animals. In summary, T2DN rats developed renal and physiological abnormalities similar to clinical observations in human patients with DKD, including progressive glomerular damage and a significant decrease in renin-angiotensin-aldosterone system plasma levels, indicating these rats are an excellent model for studying the progression of renal damage in type 2 DKD.

Sign in / Sign up

Export Citation Format

Share Document