During the formation of kidney stones, calcium oxalate crystals activate NOX4 through the renin–angiotensin–aldosterone system, generating excessive ROS, which activates the p38 MAPK pathway, increases the expression of inflammatory factors osteopontin (OPN) and monocyte chemoattractant protein-1 (MCP-1), promotes the adhesion of calcium oxalate crystals and the formation of kidney stones [10,11,12,13]. The gene discussed is REN; the disease is nephrolithiasis.