Prevention of Chemotherapy-Induced Nephrotoxicity in Children with Cancer

Children with cancer treated with cytotoxic drugs are frequently at risk of developing renal dysfunction. The cytotoxic drugs that are widely used for cancer treatment in children are cisplatin (CPL), ifosfamide (IFO), carboplatin, and methotrexate (MTX). Mechanisms of anticancer drug-induced renal disorders are different and include acute kidney injury (AKI), tubulointerstitial disease, vascular damage, hemolytic uremic syndrome (HUS), and intrarenal obstruction. CPL nephrotoxicity is dose-related and is often demonstrated with hypomagnesemia, hypokalemia, and impaired renal function with rising serum creatinine and blood urea nitrogen levels. CPL, mitomycin C, and gemcitabine treatment cause vascular injury and HUS. High-dose IFO, streptozocin, and azacitidine cause renal tubular dysfunction manifested by Fanconi syndrome, rickets, and osteomalacia. AKI is a common adverse effect of MTX, interferon-alpha, and nitrosourea compound treatment. These strategies to reduce the cytotoxic drug-induced nephrotoxicity should include adequate hydration, forced diuresis, and urinary alkalization. Amifostine, sodium thiosulfate, and diethyldithiocarbamate provide protection against CPL-induced renal toxicity.