Extracellular Vesicles in Acute Kidney Injury: Mechanisms, Biomarkers, and Therapeutic Potential

Abstract

Acute kidney injury (AKI) has a high morbidity and mortality rate but can only be treated with supportive therapy in most cases. The diagnosis of AKI is mainly based on serum creatinine level and urine volume, which cannot detect kidney injury sensitive and timely. Therefore, new diagnostic and therapeutic molecules of AKI are being actively explored. Extracellular vesicles (EVs), secreted by almost all cells, can originate from different parts of the kidney and mediate intercellular communication between various cell types of nephrons. At present, numerous successful EV-based biomarker discoveries and treatments for AKI have been made, such as the confirmed diagnostic role of urine-derived EVs in AKI and the established therapeutic role of mesenchymal stem cell-derived EVs in AKI have been confirmed; however, these related studies lack a full discussion. In this review, we summarize the latest progression in the profound understanding of the functional role of EVs in AKI caused by various etiologies in recent years and provide new insights into EVs as viable biomarkers and therapeutic molecules for AKI patients. Furthermore, the current challenges and prospects of this research area are briefly discussed, presenting a comprehensive overview of the growing foregrounds of EVs in AKI.

Keywords: acute kidney injury; diagnostic biomarkers; extracellular vesicles; mesenchymal stem cells; therapeutic molecules.

Figure 1

Role of EVs in intra-nephron communication. The EVs secreted by the parental cells reach the kidneys, transporting the carried biomolecules to the recipient cells. In the left half of the image, the parent cell section shows the process of EV formation. In the middle of the picture, the EVs secreted by the parental cells can interact with all the cells of the kidney and the EVs they secrete, and together affect the progression of kidney disease. At the bottom of the middle section is a microscopic amplification of EVs. In the right part of the image, the receptor cell receives the biomolecules carried by the parental cell-derived EVs. Created in BioRender. Yan, Q. (2025) https://BioRender.com/l94g381.

Figure 2

The extraction and characterization diagram of EVs. The three source EVs mentioned in the review must undergo a series of sequential processes to determine EVs, including the isolation and characterization of exosomes. Created in BioRender. Yan, Q. (2025) https://BioRender.com/g4unxkb.

Figure 3

The mechanism of EVs in AKI. IRI-AKI: After using AIEgens to treat MSC-EVs, MSC-EVs-transferred miRNA-200a-p activated the Keap1-Nrf2 signaling pathway in TECs, thereby restoring renal function in IRI-AKI mice. S-AKI: FRC-EVs were modified with LTH-targeting peptides to navigate EVs to tubule cells, and CD5L in EVs was released into tubule cells to promote mitophagy, inhibit pyroptosis, and thus improve kidney injury. CDDP-AKI: The crosstalk between macrophages and TECs promotes disease progression in a CDDP-AKI mouse model, and autophagy-deficient macrophage (Atg7Δmye mice derived macrophage)-derived EVs damage the mitochondria of TECs in vitro, which possibly through the miR-195a-5p-SIRT3 axis. Created in BioRender. Yan, Q. (2025) https://BioRender.com/x59y496.

Figure 4

EVs from laboratory investigation to clinical application. The clinical application of EVs faces many challenges, but there have been studies on clinical patients. We believe that the clinical application of EVs in AKI can be realized in the near future. Created in BioRender. Yan, Q. (2025) https://BioRender.com/u72t307.