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-TNFα	Infliximab	Animal models/other indications
Anti-TGFβ	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-α: tumor necrosis factor α; TGF-β, transforming growth factor β; CTG: connective tissue growth factor; miRNA: microRNA; RAGE: receptor of advance glycation end-products.