We will summarize and explore the molecular and clinical scenarios of sodium-glucose cotransporter 2 inhibitors (SGLT-2i), non-steroidal MRAs, and inhibitors of the HIF1-PHD pathway (HIF1-PHI), focusing on their current and future clinical perspectives for kidney fibrosis and their impact on the management of CKD (Figure 1). This evidence concerns the gene HIF1A and chronic kidney disease.