Vol. 9, Issue 12, Part F (2025)

Cellular senescence and fibrosis have become central to the long-term effects that ensue Acute Kidney Injury (AKI), where it was previously viewed as a reversible clinical outcome to a significant risk factor of Chronic Kidney Disease (CKD). In AKI, there is a marked level of oxidative stress, mitochondrial dysfunction and DNA damage in tubular epithelial cells, which can drive the process of senescence involving a permanent cell-cycle arrest with subsequent release of pro-inflammatory mediators, the Senescence-Associated Secretory Phenotype (SASP). Although such a reaction is beneficial to curb the spread of damaged cells, chronic senescence interferes with the regeneration of normal tissues by heightening inflammation, inhibiting epithelial repair, and enhancing a maladaptive microenvironment. The SASP factors enhance fibroblast recruitment and activation, which hastens interstitial fibrosis the technologic of permanent structural injury in the post-AKI kidney. Myofibroblasts then extracellularly deposit too much extracellular matrix that leads to progressive scarring, diminished nephron operations, and gradual loss of renal reserve. Notably, senescence and fibrosis are mutually reinforcing; fibrogenesis is stimulated by senescent cells and the rigid and hypoxic fibrotic niche increases senescence in neighboring epithelial and stromal cells, and is a self-perpetuating mechanism that contributes to AKI-to-CKD progression. Potential methods of breaking this vicious cycle of pathological loops include new forms of therapeutic treatment, including senolytic therapy to selectively kill senescent cells, SASP inhibitors to reduce inflammatory signaling and anti-fibrotic therapy to suppress the activity of myofibroblasts. The additional conception of the crossroad of senescence and fibrosis provides a vital understanding of the importance of maladaptive repair of the kidney and provides new opportunities to prevent long-term kidney damages after acute kidney damage.