Apoptotic Bodies in Kidney Disease: Orchestrators of Inflammation, Fibrosis, and Repair.

Abstract

Apoptotic bodies are membrane-bound vesicles generated during the terminal stages of programmed cell death and are traditionally viewed as inert cellular debris. Emerging evidence, however, positions apoptotic bodies as dynamic mediators of intercellular communication with critical roles in kidney physiology and pathology. In the healthy kidney, efficient efferocytosis of apoptotic bodies maintains tissue homeostasis by ensuring immunologically silent clearance of apoptotic remnants. In AKI, extensive tubular epithelial apoptosis generates a high burden of apoptotic bodies that can amplify inflammation, endothelial dysfunction, and adaptive immune activation when clearance is impaired, yet promote resolution and epithelial repair when efficiently removed. In CKD, persistent low-grade apoptosis combined with defective efferocytosis leads to progressive accumulation of apoptotic bodies in the interstitium, where their bioactive cargo-including damage-associated molecular patterns, cytokines, growth factors, and profibrotic microRNAs-drives fibroblast activation, extracellular matrix expansion, and fibrosis. In the vasculature, apoptotic bodies derived from vascular smooth muscle cells act as nucleation sites for calcium-phosphate crystal deposition, linking apoptosis to the development of medial vascular calcification in CKD. Together, these findings highlight apoptotic bodies as active regulators of injury, inflammation, fibrosis, regeneration, and vascular pathology. Understanding the determinants of their pathogenic versus reparative effects could yield new biomarkers and therapeutic strategies, including modulation of efferocytosis, targeting apoptotic body-derived signaling pathways, and engineering apoptotic bodies-based delivery systems.