Novel Therapeutic Strategies for Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is a growing global public health problem. The implementation of evidence-based clinical practices merely defers the development of kidney disease. Photobiomodulation (PBM) reduces oxidative stress, inflammation, and tissue fibrosis. However, the potential effects and underlying mechanisms of the PBM in kidney disease are yet to be elucidated. Human proximal tubular cells (HK2) induced by transforming growth factor β1 (TGF-1) were used as an in vitro CKD model. Two mouse models induced by folic acid (FA) were conducted for preventive and therapeutic studies, respectively. Finally, a diabetic kidney disease (DKD) model induced by a high-fat diet (HFD) was carried out.In vitro results showed that TGF-β1 induced excessive oxidative stress, overexpression inflammation, and fibrosis, which was significantly reversed by low dose PBM (PBM_L), which partially inhibited Smad3, p38, Erk1/2, and PI3K/AKT/mTOR and NF-κB signalling pathways.In the preventative and therapeutic FA-induced nephropathy models, results showed significantly increased kidney/body weight ratio levels, blood urea nitrogen (BUN), urinary albumin-creatinine ratio (UACR), and the tubular injury marker KIM-1, which were significantly reversed by PBM_L. FA-induced overexpression of fibrotic and inflammatory markers was reversed by PBM_L, but increased antioxidants. Those improvements may be related to the advanced mitophagy, upregulated peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) expression by PBM_L, a reduction in TGF-β1 levels, and macrophage infiltration. In DKD mouse models, results showed that PBM_L improved HFD-induced kidney injury with significant decreases in BUN, 24-hour albumin, and UACR, which were partially via anti-fibrosis and anti-inflammation.In conclusion, the results in this thesis first investigated the renoprotective and therapeutic effects and relevant mechanisms of PBM in in vitro and in vivo CKD models.