Early-Life Oxidative Stress and Pediatric Kidney Disease: From Developmental Programming to Preventive Strategies

Abstract

The first 1000 days of life represent a critical window for renal development and long-term kidney health. During this period, oxidative stress and mitochondrial dysfunction may disrupt nephrogenesis, renal maturation, and redox-sensitive developmental pathways, potentially contributing to reduced nephron endowment and greater susceptibility to hypertension and chronic kidney disease later in life. This narrative review examines prenatal, perinatal, and early postnatal factors that may contribute to oxidative renal injury, including maternal metabolic and nutritional conditions, prematurity, impaired fetal growth, perinatal interventions, early-life nutritional and inflammatory factors, and environmental exposures. Particular attention is given to the concept of renal vulnerability and to the distinction between clinical evidence of long-term kidney risk and experimental evidence supporting potential mechanisms of developmental renal programming. Clinical cohort data indicate an increased risk of kidney disease later in life following prematurity and impaired fetal growth, although these associations do not establish oxidative stress as a causal mediator. We also discuss preventive and emerging reprogramming strategies. While mitochondrial-targeted, nutritional, and antioxidant approaches remain promising, current evidence is predominantly preclinical and does not support routine antioxidant supplementation or screening for oxidative stress biomarkers in children. From a practical pediatric perspective, early identification of relevant risk factors, appropriate clinical assessment, optimization of modifiable exposures, and individualized referral to pediatric nephrology represent the most clinically relevant strategies for protecting long-term kidney health.