Recent key advances in the understanding of the pathogenesis of childhood minimal change disease

Minimal change disease (MCD) is the leading cause of idiopathic nephrotic syndrome in children, accounting for >85% of cases in those aged 1–12 years. Although 80%–90% of patients achieve initial remission with glucocorticoids, steroid dependence or frequent relapses occur in 55%–60% of cases, necessitating prolonged immunosuppression. Long-term steroid exposure in children is associated with severe age-specific adverse events, including growth retardation, skeletal dysplasia, cataracts, and impaired vaccine responses from immunosuppression. Steroid resistance and chronic kidney disease may also develop in some patients. Recent clinical evidence and literature (2015–2025) have transformed our understanding of MCD from the traditional “single T cell-driven” hypothesis to a multidimensional interactive regulatory network. This network is based on coordinated Tand B-cell dysregulation, mediated by defined podocyte injury pathways and modulated by genetic and environmental factors. Distinct pediatric traits stem from immature immune system development and pediatric podocyte plasticity. In this review, we synthesize recent advances in these pediatric pathogenic mechanisms, delineate age-dependent differences between childhood and adult MCD, and propose a precision medicine framework for disease subtyping, noninvasive biomarker development, and targeted therapies. This work addresses critical unmet clinical needs in the long-term management of pediatric MCD.