Chronic kidney disease (CKD) is an increasing cause of morbidity and mortality worldwide. Besides the higher prevalence of diabetes, hypertension and aging worldwide, immune mediated disorders remain an important cause of kidney disease and are especially prevalent in young adults. Regardless of the initial insult, final pathway to CKD and kidney failure is always the loss of normal tissue and fibrosis development, in which the dynamic equilibrium between extracellular matrix synthesis and degradation is disturbed, leading to excessive production and accumulation. During fibrosis, a multitude of cell types intervene at different levels, but myofibroblasts and inflammatory cells are considered critical in the process. They exert their effects through different molecular pathways, of which transforming growth factor β (TGF-β) has demonstrated to be of particular importance. Additionally, CKD itself promotes fibrosis due to the accumulation of toxins and hormonal changes, and proteinuria is simultaneously a manifestation of CKD and a specific driver of renal fibrosis. Pathways involved in renal fibrosis and CKD are closely interrelated, and although important advances have been made in our knowledge of them, it is still necessary to translate them into clinical practice. Given the complexity of this process, it is highly likely that its treatment will require a multi-target strategy to control the origin of the damage but also the mechanisms that perpetuate it. Fortunately, rapid technology development over the last years and new available drugs in the nephrologist's armamentarium give reasons for optimism that more personalized assistance for CKD and renal fibrosis will appear in the future.
Keywords: Multitarget therapy; Myofibroblast; Proteinuria; Renal fibrosis; SGLT2 inhibitors; TGF-β.
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