Nephrotoxicity of Cancer Treatment in Children

Roderick Skinner

Disclosures

Pediatr Health. 2010;4(5):519-538. 

In This Article

Epidemiology of Nephrotoxicity in Children with Cancer

Most information regarding the frequency of renal damage in children with cancer has investigated acute or chronic renal toxicity in cohorts of patients treated with well-known or putative nephrotoxins. The prevalence of nephrotoxicity in such investigations has varied widely, with examples ranging from studies reporting no renal toxicity (e.g., in initial studies of standard dose carboplatin[6]) to those describing a very high prevalence of subclinical renal damage (e.g., 88%, manifest by tubular glycosuria, in children treated with ifosfamide[7]) and even the universal development of nephrotoxicity (e.g., hypomagnesemia due to tubular toxicity in 100% of children treated with cisplatin[8]). Numerous factors influence the frequency of nephrotoxicity in children with cancer, including the presence of pre-existing renal damage due to the malignancy itself or other causes, patient demographic features especially age, and the nature, duration and intensity (dose and dose intensity) of the nephrotoxic insult itself, which may be due to anticancer treatment (chemotherapy or other anticancer drugs, radiotherapy or surgery) or supportive treatment (e.g., anti-infective drugs) (Box 1 & 2).

In contrast to the numerous studies of nephrotoxicity in selected patient cohorts receiving particular treatments, very little information is available to describe the frequency of chronic renal dysfunction in unselected cohorts of children treated for the whole spectrum of childhood malignancy. Recent preliminary data from the CCSS found that severe renal chronic disease (i.e., grade 3–4) was uncommon, being present in only 0.8% of long-term survivors (>5 years since treatment completion and >18 years of age) but this was significantly more common than in their siblings (0.2%, relative risk [RR]: 8.1; 95% CI: 2.9–23.1).[9] Although grade 1–4 renal chronic disease was present in 10.1% of survivors, it was also observed in 8.5% of these survivors' siblings, giving an odds ratio of disease of only 1.5 (95% CI: 1.3–1.8). The high frequency of abnormalities in siblings is presumably due to the very broad definition of renal chronic disease employed in the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 3.0, which includes symptoms such as urinary frequency, urgency and urine color change that are common in the general otherwise healthy population.

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