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Diabetic nephropathy: an insight into molecular mechanisms and emerging therapies.
- Source :
-
Expert opinion on therapeutic targets [Expert Opin Ther Targets] 2019 Jul; Vol. 23 (7), pp. 579-591. Date of Electronic Publication: 2019 Jun 03. - Publication Year :
- 2019
-
Abstract
- Introduction : Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes and is the most common cause of proteinuric and non-proteinuric forms of end-stage renal disease (ESRD). Control of risk factors such as blood glucose and blood pressure is not always achievable or effective. Significant research efforts have attempted to understand the pathophysiology of DKD and develop new therapies. Areas covered : We review DKD pathophysiology in the context of existing and emerging therapies that affect hemodynamic and metabolic pathways. Renin-angiotensin system (RAS) inhibition has become standard care. Recent evidence for renoprotective activity of SGLT2 inhibitors and GLP-1 agonists is an exciting step forward while endothelin receptor blockade shows promise. Multiple metabolic pathways of DKD have been evaluated with varying success; including mitochondrial function, reactive oxygen species, NADPH oxidase (NOX), transcription factors (NF-B and Nrf2), advanced glycation, protein kinase C (PKC), aldose reductase, JAK-STAT, autophagy, apoptosis-signaling kinase 1 (ASK1), fibrosis and epigenetics. Expert opinion : There have been major advances in the understanding and treatment of DKD. SGLT2i and GLP-1 agonists have demonstrated renoprotection, with novel therapies under evaluation. Addressing the interaction between hemodynamic and metabolic pathways may help achieve prevention, attenuation or even reversal of DKD.
- Subjects :
- Animals
Blood Glucose drug effects
Diabetic Nephropathies physiopathology
Drug Development
Glucagon-Like Peptide 1 agonists
Humans
Kidney Failure, Chronic etiology
Renin-Angiotensin System drug effects
Risk Factors
Sodium-Glucose Transporter 2 Inhibitors pharmacology
Diabetic Nephropathies drug therapy
Hypoglycemic Agents pharmacology
Kidney Failure, Chronic drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1744-7631
- Volume :
- 23
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Expert opinion on therapeutic targets
- Publication Type :
- Academic Journal
- Accession number :
- 31154867
- Full Text :
- https://doi.org/10.1080/14728222.2019.1624721