Table 2.

Therapeutic strategies

Agent	Category	Pathway	Disease model	Outcome	Ref.
Statin	Lipid-lowering drug	HMG-CoA reductase	CKD	↓ Proteinuria, histologic changes, oxidative stress/apoptosis, and podocyte injury	[82, 84]
Fenofibrate	Fibrate	PPARa agonist	HFD	↓ Albuminuria, histologic changes, oxidative stress/fibrosis, and lipid accumulation	[85]
Fenofibrate	Fibrate	PPARa agonist/AMPK-PGC-1-axis	db/db mice	↓ Albuminuria, histologic changes, inflammation/oxidative stress, apoptosis/fibrosis, and lipid accumulation	[86]
AdipoRon	Adiponectin receptor agonist	AMPK/PPARa pathway	db/db mice	↓ UACR, oxidative stress/apoptosis/fibrosis, and lipid accumulation	[7, 87]
JNJ 39933673	SGLT2 inhibitor	ChREBP-β, SREBP-1	db/db mice	↓ UACR, histological changes, inflammation/fibrosis, lipid accumulation, and podocyte injury	[88]
Dapagliflozin	SGLT2 inhibitor	SREBP-1c	WD-induced obesity mice	↓ UACR, histologic changes, fibrosis, lipid accumulation, and podocyte injury	[88–90]
Obeticholic acid (INT-747)	FXR agonist	Glutathione metabolism pathway	HFD + uninephrectomy	↓ UACR, histologic changes, oxidative stress/apoptosis, and lipid accumulation	[91]
INT-777	Selective TGR5 agonist	TGR5	db/db mice, DIO mice	↓ Proteinuria, histologic changes, inflammation/fibrosis, FA accumulation, podocyte injury	[92]
INT-767	FXR/TGR5 dual agonist	SREBP-1 pathway; TGF-β pathway	db/db mice, STZ-treated mice and DIO mice	↓ Proteinuria, histologic changes, fibrosis, lipid accumulation, and podocyte injury	[93]
Neutralizing monoclonal VEGF-B antibody	VEGF-B antagonism	VEGF-B signaling	Podo-VegfB KO; db/db mice; double KO; HFD or STZ-treated mice	↓ UACR, histologic changes, inflammation, lipid accumulation, and podocyte injury	[39]
Cyclosporin A2/2-hydroxypropyl-β-cyclodextrin	Calcineurin inhibitor/cholesterol chelator	TNF/NFAT/ABCA1/SOAT1 signaling	Podo-Abca1 KO, double, triple, and inducible KO mice	↓ UACR, histologic changes, inflammation/oxidative stress/apoptosis, cholesterol accumulation, and podocyte injury	[49, 58]
A30/elamipretide	ABCA1 inductor/cardiolipin peroxidase inhibitor	Mitochondrial dysfunction pathway	Podo-Abca1 KO; Soat KO, db/db and BTBR ob/ob mice	↓ UACR, histologic changes, oxidative stress/mitochondrial dysfunction, lipid accumulation, and podocyte injury	[25]
Sandoz 58-035	SOAT1 inhibitor	ABCA1/SOAT1 signaling	db/db Soat KO mice; Col4a3 KO (AS) mice	↓ UACR, histologic changes, cholesterol accumulation, and podocyte injury	[51]
Ceramide-1-phosphate	Lipid supplementation	SMPDL3b/C1P/IR/Cav-1/Akt signaling	Podo-Smpdl3 KO, double KO, and db/db mice	↓ UACR, histologicchanges, lipid accumulation, podocyte injury	[40]
Rituximab	CD20 monoclonal antibody	SMPDL3b, ASMase	Patients with recurrent FSGS, human podocytes treated with serum from patients	↓ UACR, histologic changes, lipid accumulation, and podocyte injury	[74]
Berberine	Flavonoid	Drp1	db/db mice	↓ UACR, histologic changes, oxidative stress, mitochondrial dysfunction, lipid accumulation, and podocyte injury	[32]

Ref., reference; HMG-CoA, β-hydroxy-β-methylglutaryl-coenzyme A; CKD, chronic kidney disease; PPAR, peroxisome proliferator-activated receptor; HFD, high-fat diet; AMPK, AMP-activated protein kinase; PGC-1, peroxisome proliferator activated receptor-gamma coactivator-1; db/db, leptin receptor-deficient; UACR, urinary albumin creatinine ratio; SGLT2, sodium-glucose cotransporter 2; ChREBP, carbohydrate-responsive element-binding protein; SREBP, sterol regulatory element-binding protein; WD, western diet; FXR, farnesoid X receptor; TGR5, G protein-coupled bile acid receptor; DOI mice, diet-induced obesity mice; TGF-β, transforming growth factor beta; STZ, streptozotocin; Podo, podocyte; VEGF-B, vascular endothelial growth factor B; SOAT1, sterol O-acyltransferase 1; KO, knockout; TNF, tumor necrosis factor; NFAT, nuclear factor of activated T-cells; SOAT1, sterol O-acyltransferase 1; ABCA1, ATP, binding cassette A1; AS, Alport syndrome; BTBR, black tan and brachyury; ob/ob, leptin-deficient; SMPDL3b, sphingomyelin phosphodiesterase acid-like 3b; C1P, ceramide-1-phosphate; IR, insulin receptor; Cav-1, caveolin-1; Akt, protein kinase B; ASMase, acid-sphingomyelinase; FSGS, focal segmental glomerulosclerosis; Drp1, dynamin-related protein 1.