Life-Course Programming of Kidney Disease: Roles of Gut Microbiota Dysbiosis and Oxidative Stress

Chronic kidney disease (CKD) affects millions globally and represents a major health burden. This narrative review adopts a life-course perspective to synthesize current evidence on CKD as a consequence of adverse early-life exposures that disrupt nephrogenesis, leading to kidney programming and reduced nephron endowment. The objective of this review is to integrate emerging mechanistic and translational evidence linking developmental programming, gut microbiota, and redox biology within a unified gut-redox axis framework, and to identify potential targets for early-life prevention of CKD. Central to this process is the gut-redox axis, a bidirectional network linking gut microbiota with host redox homeostasis. A balanced axis preserves epithelial integrity, metabolic stability, and immune regulation, whereas dysbiosis and oxidative stress form a self-perpetuating cycle that promotes CKD and related comorbidities. Maternal oxidative stress and impaired microbial transmission exacerbate early-life dysbiosis, persistent epigenetic alterations, and nephron deficits. In adulthood, protein-bound uremic toxins amplify oxidative injury and inflammation, further perturbing microbial composition. Experimental and clinical studies show that early-life interventions-including probiotics, prebiotics, postbiotics, antioxidants, and toxin-lowering strategies-can restore gut-redox balance and improve renal outcomes. These insights highlight opportunities for precision prevention and mechanism-based therapies targeting CKD across the life course.