scholarly journals Roles of mTOR in Diabetic Kidney Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 321
Author(s):  
Mako Yasuda-Yamahara ◽  
Shinji Kume ◽  
Hiroshi Maegawa
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Cell Injury ◽  
Nutrient Sensing ◽  
Diabetic Patients ◽  
Diabetic Kidney ◽  
Number Of Patients ◽  
New Treatment ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and the number of patients affected is increasing worldwide. Thus, there is a need to establish a new treatment for DKD to improve the renal prognosis of diabetic patients. Recently, it has shown that intracellular metabolic abnormalities are involved in the pathogenesis of DKD. In particular, the activity of mechanistic target of rapamycin complex 1 (mTORC1), a nutrient-sensing signaling molecule, is hyperactivated in various organs of diabetic patients, which suggests the involvement of excessive mTORC1 activation in the pathogenesis of diabetes. In DKD, hyperactivated mTORC1 may be involved in the pathogenesis of podocyte damage, which causes proteinuria, and tubular cell injury that decreases renal function. Therefore, elucidating the role of mTORC1 in DKD and developing new therapeutic agents that suppress mTORC1 hyperactivity may shed new light on DKD treatments in the future.

scholarly journals Therapeutic Strategies for Diabetic Kidney Disease

Diabetology ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 31-35
Author(s):  
Keiichiro Matoba
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Intensive Therapy ◽  
Therapeutic Strategies ◽  
Therapeutic Interventions ◽  
Hemodynamic Changes ◽  
Diabetic Kidney ◽  
Global Epidemic ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is a global epidemic leading to end-stage renal disease (ESRD) and susceptibility to cardiovascular disease, with few therapeutic interventions. A hallmark of DKD is the activation of the renin-angiotensin-aldosterone system and hemodynamic changes in glomerulus. Although intensive therapy with agents that targets those abnormalities lowers the risk of DKD progression, it does not completely abolish the risk of ESRD and cardiovascular events. Recent studies have illustrated the importance of renal inflammation, oxidative stress, and activated Rho-associated protein kinase (ROCK) signaling as essential pathogenesis for the development of DKD. In this commentary, these topics will be discussed.

Diabetic kidney disease in thedb/dbmouse

2003 ◽  
Vol 284 (6) ◽  
pp. F1138-F1144 ◽  
Author(s):  
Kumar Sharma ◽  
Peter McCue ◽  
Stephen R. Dunn
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Mouse Model ◽  
Renal Disease ◽  
Mouse Models ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Matrix Expansion ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is increasing in incidence and is now the number one cause of end-stage renal disease in the industrialized world. To gain insight into the genetic susceptibility and pathophysiology of diabetic nephropathy, an appropriate mouse model of diabetic nephropathy would be critical. A large number of mouse models of diabetes have been identified and their kidney disease characterized to various degrees. Perhaps the best characterized and most intensively investigated model is the db/ db mouse. Because this model appears to exhibit the most consistent and robust increase in albuminuria and mesangial matrix expansion, it has been used as a model of progressive diabetic renal disease. In this review, we present the findings from various studies on the renal pathology of the db/ db mouse model of diabetes in the context of human diabetic nephropathy. Furthermore, we discuss shortfalls of assessing functional renal disease in mouse models of diabetic kidney disease.

scholarly journals Significance of Metformin Use in Diabetic Kidney Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 4239 ◽  
Author(s):  
Daiji Kawanami ◽  
Yuichi Takashi ◽  
Makito Tanabe
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Experimental Studies ◽  
Glucose Lowering ◽  
Diabetic Kidney ◽  
First Line Therapy ◽  
Stage Renal Disease ◽  
End Stage ◽  
Pharmacologic Actions

Metformin is a glucose-lowering agent that is used as a first-line therapy for type 2 diabetes (T2D). Based on its various pharmacologic actions, the renoprotective effects of metformin have been extensively studied. A series of experimental studies demonstrated that metformin attenuates diabetic kidney disease (DKD) by suppressing renal inflammation, oxidative stress and fibrosis. In clinical studies, metformin use has been shown to be associated with reduced rates of mortality, cardiovascular disease and progression to end-stage renal disease (ESRD) in T2D patients with chronic kidney disease (CKD). However, metformin should be administered with caution to patients with CKD because it may increase the risk of lactic acidosis. In this review article, we summarize our current understanding of the safety and efficacy of metformin for DKD.

scholarly journals Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease

2019 ◽  
Vol 20 (14) ◽  
pp. 3393 ◽  
Author(s):  
Keiichiro Matoba ◽  
Yusuke Takeda ◽  
Yosuke Nagai ◽  
Daiji Kawanami ◽  
Kazunori Utsunomiya ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Mortality Rates ◽  
Standards Of Care ◽  
Current Status ◽  
Diabetic Kidney ◽  
Stage Renal Disease ◽  
End Stage ◽  
Current Standards

Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease (ESRD) and is therefore a major burden on the healthcare system. Patients with DKD are highly susceptible to developing cardiovascular disease, which contributes to increased morbidity and mortality rates. While progress has been made to inhibit the acceleration of DKD, current standards of care reduce but do not eliminate the risk of DKD. There is growing appreciation for the role of inflammation in modulating the process of DKD. The focus of this review is on providing an overview of the current status of knowledge regarding the pathologic roles of inflammation in the development of DKD. Finally, we summarize recent therapeutic advances to prevent DKD, with a focus on the anti-inflammatory effects of newly developed agents.

scholarly journals Targeting Redox Imbalance as an Approach for Diabetic Kidney Disease

Biomedicines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 40 ◽  
Author(s):  
Keiichiro Matoba ◽  
Yusuke Takeda ◽  
Yosuke Nagai ◽  
Tamotsu Yokota ◽  
Kazunori Utsunomiya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Public Health Problem ◽  
Cardiovascular Complications ◽  
Current Status ◽  
Diabetic Kidney ◽  
Redox Imbalance ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is a worldwide public health problem. It is the leading cause of end-stage renal disease and is associated with increased mortality from cardiovascular complications. The tight interactions between redox imbalance and the development of DKD are becoming increasingly evident. Numerous cascades, including the polyol and hexosamine pathways have been implicated in the oxidative stress of diabetes patients. However, the precise molecular mechanism by which oxidative stress affects the progression of DKD remains to be elucidated. Given the limited therapeutic options for DKD, it is essential to understand how oxidants and antioxidants are controlled in diabetes and how oxidative stress impacts the progression of renal damage. This review aims to provide an overview of the current status of knowledge regarding the pathological roles of oxidative stress in DKD. Finally, we summarize recent therapeutic approaches to preventing DKD with a focus on the anti-oxidative effects of newly developed anti-hyperglycemic agents.

scholarly journals Glomerular Diseases in Diabetic Patients: Implications for Diagnosis and Management

2021 ◽  
Vol 10 (9) ◽  
pp. 1855
Author(s):  
Nestor Oliva-Damaso ◽  
José María Mora-Gutiérrez ◽  
Andrew S. Bomback
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Treatment Strategies ◽  
Glomerular Disease ◽  
Diabetic Patients ◽  
Glomerular Diseases ◽  
Diabetic Kidney ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
New Treatment

The prevalence of diabetes continues to rise worldwide. In addition to rising rates of diabetic kidney disease, we are also seeing a parallel rise in nondiabetic kidney disease among patients with diabetes. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, membranous nephropathy, and other glomerular diseases. The management of diabetic kidney disease is rapidly evolving to include, beyond glycemic control and renin angiotensin inhibition, the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists. These and other new treatment strategies should be applicable to managing glomerular disease in diabetic patients to reduce toxicities associated with immunosuppression and, in particular, corticosteroids. The prevalence of glomerular disease in diabetic patients is underappreciated. Diagnosis and appropriately treating these diseases remain an important avenue to modify kidney outcomes in diabetic patients.

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