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.

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.

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

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.

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