Exosomes and Renal Fibrosis: Diagnostic Value, Therapeutic Potential and Challenges.

Abstract

Renal fibrosis is a key pathological process in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD), characterised by irreversible damage to the renal parenchyma. Currently, effective curative treatments are lacking. Exosomes, double-layer phospholipid vesicles containing bioactive components such as proteins, lipids, and nucleic acids, play a pivotal role in intercellular communication. Under physiological conditions, exosomes contribute to kidney development (eg regulating of ureteric bud branching and nephron formation) and maintenance of cellular homeostasis (eg protection of the glomerular filtration barrier and regulation of electrolyte balance). In pathological conditions, damaged renal tubular epithelial cells (RTECs) and other renal cell types release exosomes carrying pro-fibrotic factors (eg miR-21, TGF-β), which activate fibroblasts and facilitate excessive extracellular matrix (ECM) deposition, thereby accelerating the fibrotic process. Exosomes possess significant diagnostic value, as their protein components (eg Cp and CD2AP in urinary exosomes) and RNA cargo (eg lncRNA, miRNA, circRNA) may serve as biomarkers for renal function impairment. Therapeutically, exosomes derived from bone marrow, adipose tissue, umbilical cord, and urine can delay fibrosis through multiple mechanisms, including anti-inflammatory effects, antioxidant activity, promotion of angiogenesis, and regulation of signalling pathways (eg NOTCH, AKT). Engineered exosomes exhibit enhanced targeting and delivery efficiency through endogenous or exogenous loading methods, thereby further improving therapeutic efficacy. However, current research faces challenges including inconsistent methods of exosome isolation and purification, absence of standardised identification protocols, insufficient stability, and barriers to clinical translation. This review summarises the current progress in exosome research related to renal fibrosis, covering physiological and pathological roles, diagnostic and therapeutic potential, and existing challenges, aiming to facilitate translation from basic research to clinical practice and to provide novel strategies for precise diagnosis and treatment of renal fibrosis.