Several systems, molecules, and responses involved in the pathogenesis of fibrosis in CKD—both, core or regulatory signaling pathways—will be discussed in this review, particularly inflammation, renin-angiotensin system (RAS), parathyroid hormone (PTH), FGF23/klotho, microRNAs (miRs), and the vitamin D hormonal system. This evidence concerns the gene REN and chronic kidney disease.