Immune dysregulation in pediatric cancer-associated nephrotic syndrome: current insights

Nephrotic syndrome (NS) occurring in children with cancer represents a rare yet clinically important paraneoplastic complication. Within pediatric oncology, both primary (idiopathic) and secondary forms of glomerular disease have been identified, most frequently presenting as minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or membranous nephropathy (MN). Emerging evidence highlights the involvement of anti-nephrin autoantibodies in a significant subset of idiopathic pediatric NS cases. Nephrin, a crucial structural protein of the podocyte slit diaphragm, becomes a target in immune-mediated processes, where antibody binding or immune dysfunction disrupts podocyte integrity, leading to proteinuria. Anti-nephrin autoantibodies are well recognized in idiopathic pediatric nephrotic syndrome, but their contribution to cancer-related cases remains unproven. This review explores potential interactions between anti-nephrin immunity, childhood malignancies, and nephrotic syndrome, beginning with current insights into podocyte-specific molecular targets and the immunological roles of T and B lymphocytes. It then examines how paraneoplastic processes-such as tumor-derived cytokines and disturbed immune responses-together with the kidney toxicity of therapies including chemotherapy and immunotherapy, may drive podocyte injury in this setting. Reported associations across cancers such as leukemia, lymphoma, neuroblastoma, and Wilms tumor are summarized, emphasizing the role of adaptive immunity in glomerular damage. Diagnostic and therapeutic implications are considered, with attention to the emerging value of anti-nephrin antibodies as biomarkers and to targeted approaches, including B cell-directed treatments. The review concludes by highlighting future research priorities and the importance of coordinated nephrology-oncology collaboration to promote earlier detection, better risk assessment, and more effective management for affected children.