title: Novel therapies for diabetic kidney disease.
abstract: The number of people diagnosed with diabetes is rising throughout the world, which in turn drives upward the global frequency of diabetic kidney disease (DKD). Individuals with DKD are at an increased risk for premature death, cardiovascular disease, and other severe illnesses that result in frequent hospitalizations and increased health-care utilization. Current treatments concentrate on controlling hyperglycemia and hypertension with the specific use of renin-angiotensin system inhibitors. Although such measures reduce the risk of progressive kidney disease, DKD remains the leading cause of ESRD and the major risk amplifier for death in this population. Therefore, novel therapeutic approaches are urgently needed. Ideas for novel targets for therapy are founded on recent advances in understanding DKD mechanisms that are based on experimental models and human observations. The purpose of this review is to describe the epidemiology and present knowledge of DKD pathophysiology as the basis for novel therapies including inhibitors of Janus kinases (JAK), protein kinase C, fibrosis, advanced glycation end products treatments, and endothelin.
authors.affiliation: Providence Medical Research Center, Providence Sacred Heart Medical Center and Children's Hospital, Spokane, WA; and Providence Medical Research Center, Providence Sacred Heart Medical Center and Children's Hospital, Spokane, WA and University of Washington School of Medicine, Spokane and Seattle, WA. Electronic address: radica.alicic@providence.org.
authors.forename: Radica Z
authors.initials: RZ
authors.lastname: Alicic
authors.affiliation: Providence Medical Research Center, Providence Sacred Heart Medical Center and Children's Hospital, Spokane, WA; and Providence Medical Research Center, Providence Sacred Heart Medical Center and Children's Hospital, Spokane, WA and University of Washington School of Medicine, Spokane and Seattle, WA.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Tuttle
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D000077300:Bosentan; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D016232:Endothelins / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D008301:Maleimides / Q000627:therapeutic use; D011073:Polyamines / Q000627:therapeutic use; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011728:Pyridones / Q000627:therapeutic use; D011733:Pyridoxamine / Q000627:therapeutic use; D000069603:Sevelamer; D013449:Sulfonamides / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000959:Antihypertensive Agents; D000975:Antioxidants; D016232:Endothelins; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D007211:Indoles; D008301:Maleimides; D011073:Polyamines; D011728:Pyridones; D013449:Sulfonamides; D011733:Pyridoxamine; C099154:ruboxistaurin; D000069603:Sevelamer; C093844:pirfenidone; D053612:Janus Kinases; D011493:Protein Kinase C; D000077300:Bosentan; C560078:pamrevlumab; D000111:Acetylcysteine
keywords: Antifibrotic treatments; Antioxidant/anti-inflammatory therapy; Diabetic kidney disease; Endothelin antagonists; Protein kinase C inhibitors