Emerging therapeutic pipelines on kidney fibrosis: challenges in translational research

BACKGROUND: Chronic kidney disease (CKD) is estimated that by 2040, it will be the 5th highest cause of years of life lost globally due to the aging population and the rising prevalence of age-related diseases such as hypertension and diabetes. Therefore, a deep comprehension of the biological and molecular mechanisms underlying kidney fibrosis is urgently needed to facilitate the development of new therapeutic strategies that can hinder disease progression and simultaneously address the comorbidities associated with CKD. MAIN BODY: In the last years numerous studies have elucidated the complex interplay of various cellular and molecular pathways that contribute to the progression of kidney fibrosis. As a result, several promising therapeutic targets have been identified, paving the way for innovative treatment strategies. These include endogenous (Dickkopf-1, Klotho, and secreted frizzled-related proteins) and exogenous (ICG-001 and relaxin) modulators of the WNT/β-catenin pathway; inhibitors of TGF-β (BMP-7, ncRNA, fresolimumab); sphingosine analogs (fingolimod). In addition to these indirect approaches, therapies with direct antifibrotic activity have also gained significant attention in the field. Among these alternatives, SGLT2 inhibitors and finerenone have emerged as particularly promising options due to the favorable outcomes observed in large-scale clinical trials. These studies have highlighted their effectiveness in slowing disease progression and improving patient outcomes. CONCLUSIONS: Despite the encouraging results, additional research is necessary to fully assess the protective roles of these treatments in various clinical contexts. This review aims to synthesize the available data and current insights into this important issue.