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Pathophysiologic mechanisms in diabetic kidney disease: A focus on current and future therapeutic targets
Author(s) -
BarreraChimal Jonatan,
Jaisser Frédéric
Publication year - 2020
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13969
Subject(s) - medicine , mineralocorticoid receptor , bioinformatics , disease , diabetes mellitus , population , type 2 diabetes , kidney disease , epigenetics , pharmacology , aldosterone , endocrinology , biology , biochemistry , environmental health , gene
Diabetic kidney disease (DKD) is the primary cause of chronic kidney disease around the globe and is one of the main complications in patients with type 1 and 2 diabetes. The standard treatment for DKD is drugs controlling hyperglycemia and high blood pressure. Renin angiotensin aldosterone system blockade and sodium glucose cotransporter 2 (SGLT2) inhibition have yielded promising results in DKD, but many diabetic patients on such treatments nevertheless continue to develop DKD, leading to kidney failure and cardiovascular comorbidities. New therapeutic options are urgently required. We review here the promising therapeutic avenues based on insights into the mechanisms of DKD that have recently emerged, including mineralocorticoid receptor antagonists, SGLT2 inhibitors, glucagon‐like peptide‐1 receptor agonist, endothelin receptor A inhibition, anti‐inflammatory agents, autophagy activators and epigenetic remodelling. The involvement of several molecular mechanisms in DKD pathogenesis, together with the genetic and epigenetic variability of this condition, makes it difficult to target this heterogeneous patient population with a single drug. Personalized medicine, taking into account the genetic and mechanistic variability, may therefore improve renal and cardiovascular protection in diabetic patients with DKD.

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