<p>Chronic kidney disease of unknown aetiology (CKDu) has emerged as a major public health problem in several regions worldwide. While traditionally considered a disease of adults, the latest evidence suggests that CKDu may originate early in life. This review summarises current evidence on the epidemiology, aetiology, pathophysiology, and prevention of CKDu from a pediatric perspective. Pediatric studies from endemic regions highlight early markers of kidney injury, including albuminuria, reduced estimated glomerular filtration rate, and evidence of tubular dysfunction. Environmental exposures like unsafe drinking water, agrochemicals, and occupational or climate-related stressors interact with biological vulnerabilities such as low birth weight, malnutrition, and reduced nephron endowment to initiate subclinical kidney injury. Recurrent insults may lead to maladaptive repair, progressive tubulointerstitial fibrosis, and deterioration in kidney function. Early detection and prevention are critical in reducing long-term disease burden. Strategies include improving access to safe drinking water, minimising environmental exposures, and implementing community-based screening programs. However, challenges remain, including limited access to affordable diagnostic tools and insufficient longitudinal pediatric data. Understanding CKDu as a lifelong disease underscores the importance of early-life intervention. A comprehensive, multidisciplinary approach incorporating environmental, clinical, and public health strategies is essential to prevent disease progression and improve long-term outcomes.</p> Graphical Abstract <p></p>