Mechanisms of kidney fibrosis and routes towards therapy

Abstract

Kidney fibrosis is the final common pathway of virtually all chronic kidney diseases (CKDs) and is therefore considered to be a promising therapeutic target for these conditions. However, despite great progress in recent years, no targeted antifibrotic therapies for the kidney have been approved, likely because the complex mechanisms that initiate and drive fibrosis are not yet completely understood. Recent single-cell genomic approaches have allowed novel insights into kidney fibrosis mechanisms in mouse and human, particularly the heterogeneity and differentiation processes of myofibroblasts, the role of injured epithelial cells and immune cells, and their crosstalk mechanisms. In this review we summarize the key mechanisms that drive kidney fibrosis, including recent advances in understanding the mechanisms, as well as potential routes for developing novel targeted antifibrotic therapeutics.

Keywords: antifibrotic therapeutics; cellular crosstalk; chronic kidney disease; kidney fibrosis; single-cell RNA sequencing; spatial transcriptomics.