In chronic kidney disease (CKD), persistent NLRP3 activation drives renal fibrosis through the Transforming growth factor-β1/Smad signaling pathway and epithelial–mesenchymal transition, contributing to the progression of conditions such as diabetic nephropathy, crystal nephropathy, lupus nephritis, obesity-related fibrosis, and hypertension-induced damage. This evidence concerns the gene NLRP3 and obesity due to melanocortin 4 receptor deficiency.