Nephrotoxicity of Cancer Treatment in Children

Roderick Skinner


Pediatr Health. 2010;4(5):519-538. 

In This Article


The potential causes of chronic renal impairment in both children and adults with cancer include the malignant process itself as well as adverse effects of treatment including chemotherapy, radiotherapy, surgery, immunotherapy or supportive treatment.[13–18] The malignant disease itself may contribute to chronic renal impairment, for example by damaging normal renal tissue by tumor infiltration or urinary tract obstruction. Although tumor lysis syndrome during treatment initiation may occasionally cause chronic renal damage, most patients recover satisfactory renal function.

The kidneys' excretory function requires high renal blood flow across a large endothelial glomerular surface area followed by extremely active tubular reabsorptive and secretory transport processes, but these functions expose renal cells to toxic substances that may accumulate or undergo further intracellular metabolism. It is, therefore, unsurprising that the kidneys are highly vulnerable to toxic adverse effects from a variety of drugs, including several cytotoxic, anti-infective and other supportive care agents. Likewise, the reliance of kidney function on complex vascular structures and metabolically active cells renders renal tissue very sensitive to radiotherapy,[19,20] whilst finely tuned renal hemodynamics may be significantly disturbed by direct destruction or removal of large amounts of renal tissue, as in renal tumors or infiltration, or surgery for renal tumors.[21,22]

The cytotoxic drugs most likely to cause important chronic nephrotoxicity are ifosfamide and cisplatin. Both are widely used owing to their efficacy in many solid tumors, but may cause chronic nephrotoxicity in 30–60% of treated children. Significant renal toxicity is less frequent with other cytotoxic drugs, but may follow treatment with carboplatin, methotrexate and nitrosoureas, and occasionally with other cytotoxic drugs rarely used in children or not usually regarded as major nephrotoxins.

It is important to note that nearly all chemotherapy schedules in children incorporate several different cytotoxic drugs, often given over many months or even years, especially in patients whose disease relapses. Furthermore, most patients require many other potentially nephrotoxic drugs (e.g., aminoglycoside antibiotics or amphotericin) for supportive care. Therefore, there is much potential for additive and cumulative renal damage during the often prolonged course of a child's malignant illness and treatment.