Childhood Nephrotic Syndrome Pathogenesis and Novel Therapeutic Approaches a Narrative Review

This review aims to provide an updated overview of nephrotic syndrome (NS) in children, with a focus on its prevalence, incidence, classification, pathogenesis, molecular mechanisms, prognosis, current treatments, and gene testing. It seeks to identify gaps in the current understanding of NS, particularly in the management of steroid-resistant cases, and to encourage further research into novel therapeutic strategies. By exploring recent insights into the underlying causes and contributing factors of NS, the review aspires to support the development of more effective treatments, especially for cases where current therapies are insufficient.

Recent research in NS has highlighted several advancements. Monoclonal antibodies are emerging as potential treatments, though their effectiveness is still under evaluation. Glucocorticoids, particularly dexamethasone, remain vital due to their ability to protect podocytes by stabilizing actin filaments and preventing apoptosis. The re-emergence of ACTH shows promise for treating various NS forms, such as idiopathic membranous nephropathy, though its high cost and injection requirement pose limitations. Advances in genetic testing, especially through next-generation sequencing (NGS), have enabled more precise diagnosis and personalized treatment plans. Further research is required to confirm the safety and effectiveness of such treatments as well as to find trustworthy biomarkers for forecasting treatment outcomes and illness prognoses.

NS is a common pediatric glomerular disease where genetic mutations, particularly in NPHS1 and NPHS2, play a significant role. Genetic testing is essential for identifying these mutations, allowing for personalized treatment strategies, especially in cases of congenital and steroid-resistant NS. This approach improves outcomes by enabling targeted interventions based on the patient's specific genetic profile. However, the complexity of genetic testing and the availability of resources can be limiting factors, particularly in regions with less access to advanced diagnostic tools. Despite these advances, challenges remain in treating steroid-resistant nephrotic syndrome (SRNS). While emerging therapies, such as gene therapy and adrenocorticotropic hormone (ACTH), show promise, they are still in early development and may not be widely accessible. Additionally, the lack of reliable biomarkers to predict treatment response complicates management. Further research is needed to overcome these hurdles, aiming to develop more precise treatments and improve prognosis for SRNS patients.