Action Mechanisms and Therapeutic Targets of Renal Fibrosis - Action Mechanisms and Therapeutic Targets of Renal Fibrosis - Open Access Pub

Renal fibrosis was a chronic and progressive process affecting kidneys in chronic kidney disease (CKD), regardless of cause. Although no effective targeted therapy yet existed to retard renal fibrosis, a number of important recent advances have highlighted the cellular and molecular mechanisms underlying the renal fibrosis. The advances including TGF-β/Smad pathway, oxidative stress and inflammation, hypoxia and gut microbiota-derived from uremic solutes were highlighted that could provide therapeutic targets. New therapeutic targets and strategies that are particularly promising for development of new treatments for patients with CKD were also highlighted. DOI10.14302/issn.2574-4488.jna-18-2443 Chronic kidney disease (CKD) had a high prevalence all over the world and was closely associated with high mortality 1, 2, 3. The prevalence of CKD was estimated to be 8-16% worldwide. In patients over 64 year old, the prevalence elevated to 23.4-35.8%, indicating increasing age contributed to elevate CKD. The yearly economic costs of medicine care for patients with CKD and or end-stage renal disease over age 65 were $60 billion, representing 24% of total Medicare expenditures in 2011 in America. According to the Kidney Disease Outcomes Quality Initiative, the international guidelines define and classify CKD as decreased renal function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1.73 m2, or markers of kidney damage, or both, of at least three months duration, regardless of underlying cause 1. CKD were divided into five stages as follow: Stage 1: Kidney damage (pathological abnormalities or markers of damage including abnormalities in blood or urine tests or in imaging studies) with normal or raised glomerular filtration rate (≥90 mL per min per 1.73 m2); Stage 2: Glomerular filtration rate 60–89 mL per min per 1.73 m2 with evidence of kidney damage; Stage 3: Glomerular filtration rate 30–59 mL per min per 1.73 m2; Stage 4: Glomerular filtration rate 15–29 mL per min per 1.73 m2; Stage 5: End-stage renal failure; glomerular filtration rate <15 mL per min per 1.73 m21, 4, 5. Renal fibrosis was characterized as a common endpoint of diverse CKD which resulted in functional damage ultimately leading to terminal renal failure 6, 7, 8, 9. Renal fibrosis is generally regarded as the dark side of tissue repair mechanisms. Fibrogenesis might be involved in the tubulointerstitium resulting in tubulointerstitial fibrosis, glomeruli resulting in glomerulosclerosis or the arterial vasculature resulting in atherosclerotic lesions 5, 10. Various action