scholarly journals Dual Blockade of the Renin-angiotensin-aldosterone System in Type 2 Diabetic Kidney Disease

2016 ◽  
Vol 129 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Yan-Huan Feng ◽  
Ping Fu
2019 ◽  
Vol 317 (6) ◽  
pp. F1450-F1461 ◽  
Author(s):  
Oleg Palygin ◽  
Denisha Spires ◽  
Vladislav Levchenko ◽  
Ruslan Bohovyk ◽  
Mykhailo Fedoriuk ◽  
...  

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.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 539-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
KATSUHITO MORI ◽  
YUKO YAMAZAKI ◽  
AKINOBU OCHI ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
José María Mora-Gutiérrez ◽  
José Antonio Rodríguez ◽  
María A. Fernández-Seara ◽  
Josune Orbe ◽  
Francisco Javier Escalada ◽  
...  

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-1 ◽  
Author(s):  
Yijun Xie ◽  
Yijie Jia ◽  
Cuihua Xie ◽  
Fang Hu ◽  
Meng Xue ◽  
...  

Nefrología ◽  
2016 ◽  
Vol 36 (5) ◽  
pp. 503-509 ◽  
Author(s):  
Ivo Laranjinha ◽  
Patrícia Matias ◽  
Sofia Mateus ◽  
Filipa Aguiar ◽  
Patrícia Pereira ◽  
...  

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1754
Author(s):  
Itaru Monno ◽  
Yoshio Ogura ◽  
Jing Xu ◽  
Daisuke Koya ◽  
Munehiro Kitada

Lifestyle improvement, including through exercise, has been recognized as an important mode of therapy for the suppression of diabetic kidney disease (DKD). However, the detailed molecular mechanisms by which exercise exerts beneficial effects in the suppression of DKD have not yet been fully elucidated. In this study, we investigate the effects of treadmill exercise training (TET) for 8 weeks (13 m/min, 30 min/day, 5 days/week) on kidney injuries of type 2 diabetic male rats with obesity (Wistar fatty (fa/fa) rats: WFRs) at 36 weeks of age. TET significantly suppressed the levels of albuminuria and urinary liver-type fatty-acid-binding protein (L-FABP), tubulointerstitial fibrosis, inflammation, and oxidative stress in the kidneys of WFRs. In addition, TET mitigated excessive apoptosis and restored autophagy in the renal cortex, as well as suppressed the development of morphological abnormalities in the mitochondria of proximal tubular cells, which were also accompanied by the restoration of AMP-activated kinase (AMPK) activity and suppression of the mechanistic target of rapamycin complex 1 (mTORC1). In conclusion, TET ameliorates diabetes-induced kidney injury in type 2 diabetic fatty rats.


2018 ◽  
Vol 7 (2) ◽  
pp. 98-103
Author(s):  
Sindou Sanogo ◽  
Serge Didier Konan ◽  
Kouamé Hubert Yao ◽  
Emma Kouassi ◽  
Séry Patrick Diopoh ◽  
...  

Introduction: Diabetes mellitus is a disease whose prevalence has been steadily increasing worldwide. Objectives: To evaluate the prevalence of diabetic kidney disease and to identify the associated factors in type 2 diabetic patients. Material and Methods: This was a descriptive and analytical cross-sectional study. The study was conducted over a period from January to June 2016, among patients with type 2 diabetes, followed up at the Division of Diabetology of the University Hospital of Treichville, Abidjan. Results: Of 154 included patients, diabetic nephropathy (DN) was observed in 40 cases (25.9% prevalence). We observed a female predominance (sex ratio; 0.17) and the mean age of 57.7 ± 11 years. Based on the K/DOQI guidelines, half of our patients had stage 3 kidney disease. Complications such as diabetic retinopathy (100%), hypertension (HT) (75%), dyslipidemia (45%) and obesity (30%) were found. Factors such as female sex (P = 0.001; OR [95% CI] = 4.76 [1.85-12.19]), a range 55-65 years old (P = 0.010; OR [95% CI] = 2.64 [1.26-5.53]), obesity (P = 0.012; OR [95% CI] = 3.06 [1.27-7.36]), hypertension (P = 0.0001; OR [95% CI] = 4.77 [2.12-10.71]) and HbA1c <7% (P = 0.002; OR [94% CI] = 3.42 [1.57-7.44]) were associated with nephropathy by multivariate analysis. Conclusion: the prevalence of diabetic kidney disease is high in our study. The associated factors are non-modifiable such as female gender and age, but also modifiable such as obesity and hypertension.


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