Present and Future in the Treatment of Diabetic Kidney Disease

Table 2

Summary of main pathogenic pathways and agents under evaluation for diabetic nephropathy.

Mechanism	Agent	Situation
Endothelin-receptor antagonism
	Avosentan; Atrasentan	Stopped due to adverse events; Ongoing RCT
Antioxidant agents
Direct renal effect	N-Acetylcysteine; Probucol	Inconclusive results; Apparent positive results
Xanthine oxidase inhibition	Allopurinol; Febuxostat	Ongoing RCT; Ongoing RCT
Transcription factor modulation
Protein kinase modulation	Ruboxistaurin; Imatinib; Fasudil	Stopped due to adverse events; Animal models/other indications; Animal models
JAK-STAT pathway inhibition	Baricitinib	Ongoing RCT
Neurohormonal modification	D3-RA; Sarpogrelate; ACTH	Animal models; Ongoing RCT; Ongoing RCT
Endogenous agents	Apelin; Activated protein C	Animal models; Animal models
Antifibrotic agents
Anti-TNF	Infliximab	Animal models/other indications
Anti-TGF	Pirfenidone; Fresolimumab	Stopped due to adverse events; Ongoing RCT
Anti-CTGF	FG3019	Animal models
Chemokine inhibition	CCX 140-B and others	Ongoing RCT
MMP inhibition	Tetracyclines; XL081, XL874	Ongoing RCT; Limited efficacy
miRNA modulation	LNA-anti-miR-192	Animal models
Other agents
RAGE inhibition	Pimagedine; Pyridoxamine	Stopped due to adverse events; Ineffective
Oral adsorbents	Kremezin	Moderate efficacy
Urotensin-II inhibition	Palosuran	Ineffective
Glycosaminoglycans	Sulodexide	Ineffective

RCT: randomized controlled trial; JAK-STAT: Janus kinase-signal transducer and activator of transcription; ACTH: adrenocorticotropic hormone; TNF-: tumor necrosis factor ; TGF-, transforming growth factor ; CTG: connective tissue growth factor; miRNA: microRNA; RAGE: receptor of advance glycation end-products.