Microparticles at the crossroads of the gut-kidney axis: Mechanistic drivers and therapeutic horizons in hemodialysis

Figure 1 Biogenesis and functional roles of extracellular vesicles. Exosomes (depicted in yellow; 30-100 nm in diameter) are generated within multivesicular bodies (MVBs) as intraluminal vesicles and are secreted upon fusion of the MVB with the plasma membrane. In contrast, microparticles [microparticles (MPs); shown in blue; 100-1000 nm] arise through direct outward budding of the plasma membrane and are enriched in cytosolic content and phospholipid components. Both classes of extracellular vesicles (EVs) contribute to intercellular communication by facilitating antigen presentation (via major histocompatibility complex peptide complexes), transferring surface receptors, or directly modulating signaling pathways. Additionally, EVs act as carriers for functional cargo such as proteins, transcription factors, and regulatory RNAs (including microRNAs and messenger RNAs). The precise mechanisms underlying EV uptake remain incompletely characterized, but may involve: (1) Receptor binding; (2) Endocytosis or micropinocytosis; and (3) Direct membrane fusion-mediated signaling. Created by BioRender. MVB: Multivesicular bodies.

Figure 2 Role of microparticles in the gut-kidney axis in chronic kidney disease. This schematic diagram illustrates the pivotal role of microparticles (MPs) in mediating the gut-kidney dialogue in chronic kidney disease (CKD). It depicts how gut dysbiosis compromises the intestinal barrier, leading to a “leaky gut” that facilitates the translocation of bacterial MPs and lipopolysaccharide into the circulation. These gut-derived MPs, along with uremic toxins (e.g., indoxyl sulfate, p-cresyl sulfate) produced by the kidney contribute to systemic pathology. The figure further shows MPs shed from endothelial cells, platelets, and leukocytes, carrying pro-inflammatory cytokines, oxidized lipids, and other pathogenic cargos. These MPs drive endothelial dysfunction, renal inflammation, oxidative stress, and fibrosis, amplifying CKD progression. The diagram highlights the amplifying effects of uremic toxins, metabolic acidosis, and sympathetic activation on MP-mediated damage, culminating in increased cardiovascular risk. Created by BioRender. LPS: Lipopolysaccharide; ROS: Reactive oxygen species.