An imbalance exists between renal tubular epithelial cells (RTECs) injury and repair in kidney stone disease, yet the underlying mechanism remains largely unclear. Here, we found that gasdermin D (GSDMD)-mediated pyroptosis occurred in both patients and mice with calcium oxalate (CaOx) nephrolithiasis, and the expression levels of NOD-like receptor protein 3 (NLRP3) and GSDMD were associated with the severity of kidney stones. Deficiency of GSDMD alleviated renal tubule damage and inflammatory response, ultimately inhibiting renal injury and crystal deposition. Additionally, we found that charged multivesicular body protein 4B (CHMP4B)-dependent cell repair was activated during pyroptosis of RTECs
however, the enhancement was insufficient to offset the damage. Importantly, Ca