Protecting kidney function: from mechanisms to therapeutic targets and traditional Chinese medicine

Chronic kidney disease (CKD) has been a significant public health concern globally with its prevalence increasing yearly. Renal fibrosis is the ultimate outcome of CKD progression to end-stage renal disease. However, effective treatment for renal fibrosis is lacking. Therefore, exploring the pathogenesis of renal fibrosis and targeted drugs is of great importance. In this review, we provided an overview of current research advances in the mechanisms of renal fibrosis, summarized the promising therapeutic strategies for delaying CKD progression and proposed possible research priorities in the future. First of all, renal fibrosis is characterized by a complex network composed of various cytokines, inflammatory mediators, and signaling pathways. Employing cutting-edge technologies, such as single-cell RNA sequencing for cell-type-specific fibrosis markers and utilizing big data to develop innovative algorithms, could enhance early diagnostic capabilities and guide stratification. In addition, compared with Western medicine, the diverse active ingredients found in traditional Chinese medicine (TCM) have distinct advantages in modulating the networks of renal fibrosis. Therefore, purifying the effective components of TCM and synthesizing the corresponding compounds might become a hotspot in future research. Adaptive design and using human kidney organoid models for drug screening can determine the active ingredients efficiently. Combination regimens may provide better efficacy by reducing the dosage of a single drug and alleviating the side effects. Moreover, epigenetic reprogramming is expected for the complete treatment of renal fibrosis. Finally, how to address the potential toxicity and off-target effects of pathway inhibitors or TCM compounds still remains a challenge.