The Onset and Resolution of Renal Fibrosis: A Human Perspective

Abstract Renal fibrosis is a common hallmark of chronic kidney disease (CKD) and a major determinant of progressive renal function loss. Angiotensin II (Ang II), transforming growth factor-β1 (TGF-β1), and their downstream effector, connective tissue growth factor (CTGF), have a key role in the onset and progression of renal fibrosis. Recent advances in the field have disclosed endogenous counter-regulators of Ang II and TGF-β1 signaling intrinsic to the renin–angiotensin system (RAS) and TGF-β superfamily that may hold therapeutic potential for fibrotic kidney disease. An RAS blockade-based multimodal approach is the current treatment in CKD patients, and drugs targeting TGF-β and CTGF have entered phase I and II clinical trials. Epigenetic control of renal fibrogenesis affects individual heterogeneity of progression rates of CKD. Smad3-dependent miRNAs may offer fine-tuning regulation in TGF-β–mediated fibrosis and may represent novel targets for future therapeutic approach. Epigenetic therapeutics is still at a preclinical experimentation stage.