Society of Diabetic Nephropathy Prevention Journal of Nephropathology 2251-8363 16 1 2027 01 01 Pediatric onconephrology; mechanisms of renal involvement, treatment toxicity, and mitigation strategies e28772 e28772 10.34172/jnp.28772 EN Paniz Pourpashang https://orcid.org/0000-0003-4469-086X Journal Article 10.34172/jnp.28772 2026 06 17 2026 10 01 Pediatric onconephrology has emerged as a critical subspecialty at the intersection of pediatric oncology and nephrology, driven by the remarkable increase in childhood cancer survival rates and the subsequent recognition of long-term renal morbidity. Understanding the complex interplay between oncological disease and renal pathophysiology is necessary. Renal involvement in pediatric malignancies arises through diverse mechanisms, including direct neoplastic infiltration, paraneoplastic glomerulopathies, and metabolic emergencies such as spontaneous or treatment-induced tumor lysis syndrome. Furthermore, the therapeutic armamentarium for childhood cancers is frequently nephrotoxic. Conventional chemotherapeutic agents, notably cisplatin, ifosfamide, and high-dose methotrexate, predominantly cause acute tubular necrosis and Fanconi syndrome, while novel targeted therapies and immune checkpoint inhibitors introduce new patterns of injury, including thrombotic microangiopathy and immune-mediated interstitial nephritis. These insults can lead to irreversible chronic kidney disease, hypertension, and electrolyte wasting, profoundly impacting long-term survivorship. Mitigation strategies require a proactive, multilayer approach encompassing risk stratification, aggressive peri-treatment hydration, and the judicious use of pharmacological protectants such as mesna and amifostine. Dose modulation based on real-time glomerular filtration rate assessments and the emerging utilization of novel urinary biomarkers for early subclinical tubular injury detection are necessary for timely intervention. In severe cases, temporary or permanent renal replacement therapy may be necessitated. Finally, optimizing outcomes in pediatric onconephrology demands rigorous long-term monitoring and comprehensive survivorship care plans to preserve renal function, minimize late effects, and ensure the highest possible quality of life for childhood cancer survivors.