Developmental Programming of Kidney Disease Across the Life Course: A Narrative Review Focused on Inflammation

Chronic kidney disease (CKD) represents a major global health burden, with growing evidence indicating that its origins extend back to early developmental stages. This narrative review integrates epidemiological, clinical, and mechanistic experimental evidence to position inflammation as a life-course driver of kidney vulnerability rather than a late-stage consequence. Inflammation has emerged as a central mechanistic link connecting adverse prenatal and postnatal exposures to lifelong kidney vulnerability. We highlight the translational potential by identifying pathways amenable to early-life interventions that could modify disease trajectory. During fetal development, maternal nutritional status, metabolic stress, and inflammatory exposures influence nephron endowment, immune maturation, and epigenetic regulation, thereby shaping long-term CKD risk. In childhood, early immune dysregulation and low-grade inflammation contribute to disease initiation, defining critical windows for preventive and renoprotective interventions that can be implemented in at-risk populations. In adulthood and aging, persistent activation of cytokine signaling, inflammasomes, oxidative stress pathways, autophagy-mitophagy imbalance, and cellular senescence drives progressive kidney injury, further amplified by gut microbiota dysbiosis and renin-angiotensin system interactions. Emerging life-course strategies include maternal nutrition optimization, early-life risk stratification, targeted anti-inflammatory and immunomodulatory therapies, and microbiota-directed interventions tailored to developmental stage and individual risk profile. By emphasizing inflammation as a developmentally programmed and preventable process, this review underscores opportunities for early-life and transgenerational CKD prevention, translating mechanistic insights into actionable strategies for preventive medicine and public health.