Unraveling New Mechanisms of Renal Fibrosis With Potential Therapeutic Implications
See related article, pp 350–360
Disease-related injury in any organ triggers a complex cascade of cellular and molecular responses that culminates in tissue fibrosis. When this process progresses for a prolonged period of time, parenchymal scarring and ultimately cellular dysfunction and organ failure ensue. In this conceptual framework, renal fibrosis corresponds to the replacement of renal functional tissue by extracellular matrix proteins, mainly fibrillary collagens, which lead to chronic kidney disease (CKD) and ultimately to chronic kidney failure that represents the end-stage renal disease. The concept of reversing CKD has been intensively researched during the past decade. Indeed, because the prevalence of end-stage renal disease is constantly on the rise, the lack of established antifibrotic therapies is a considerable unmet need in clinical practice. To date, the possibility of effective antifibrotic treatment has been established in experimental models of CKD, and although multiple antifibrotic compounds targeting various components of the fibrotic pathway are being assessed in clinical trials, the available results show that they are ineffective or only slightly successful to prevent or reverse renal fibrosis. Hence, it is essential to understand the pathogenesis of renal fibrosis and to discover and better understand new strategies for treating this lesion from its earliest phases.
As in other organs, the mechanistic hallmark of renal fibrosis is the accumulation of a large number of matrix-producing cells or myofibroblasts. These cells are derived from diverse origins, such as resident fibroblasts, vascular …