Recent advances in the treatment of childhood cancer are increasing long-term survival rates. Their good fortune these patients may experience, however, may come at a price: childhood cancer survivors face a life-long risk of impaired renal function, according to a recent study conducted in The Netherlands.1
“Current knowledge suggests childhood cancer survivors have an increased risk for impaired kidney function after specific cancer therapies; however, it was not known whether their kidney function recovers with time or if it gets worse,” said lead author Renée Mulder, PhD, research associate in the Department of Pediatric Oncology at Emma Children’s Hospital/Academic Medical Center in Amsterdam.
To investigate this issue, Dr. Mulder and her colleagues recruited 1,122 subjects 18 years of age or older who had cancer as children and survived at least 5 years after diagnosis. Subjects underwent a median of six measurements of glomerular filtration rate (GFR) over a median of 7.3 years.
Of the total cohort, 678 subjects were treated with potentially nephrotoxic therapy and 444 were not. Results showed a steady decline of GFR in both groups, beginning within 5 years after diagnosis and persisting for at least 30 years, and was consistently lower in subjects who received nephrotoxic therapy.
Treatment with cisplatin was associated with lower GFR, and the effect was related to cumulative cisplatin dose, especially doses 500 mg/m2 or higher. High-dose cisplatin treatment accelerated the deterioration in GFR for as long as 25 years after the diagnosis of childhood cancer.
High-dose cyclophosphamide treatment also accelerated the long-term decline in GFR, although to a lesser extent than high-dose cisplatin. Although treatment with ifosfamide or carboplatin was also associated with lower GFR, it was not associated with an increase in the rate of decline. Higher doses of ifosfamide had a greater effect on GFR, but no dose effect was seen for carboplatin. High-dose methotrexate and radiotherapy had no apparent effect on renal function.
Patients who underwent nephrectomy had lower GFR than those who didn’t; those who had a nephrectomy at an older age had a faster decline in GFR than those who had the procedure at a younger age. The authors speculated that this might have occurred because a younger kidney has a greater functional reserve capacity than an older kidney.
The probability of glomerular dysfunction up to 35 years after diagnosis was 26.4% in subjects who had nephrotoxic therapy and 6.6% in subjects who did not.
“We found that the kidney function of childhood cancer survivors treated with nephrotoxic therapy declines very soon after treatment and does not recover,” Dr. Mulder said. “Health care providers and survivors should be aware of the increased risk of early kidney damage after nephrotoxic treatment for childhood cancer, because these patients are also at increased risk for developing comorbidities, such as cardiovascular disease.”
In the general population, decline in GFR is considered a normal consequence of aging. Longitudinal data on GFR are not available, therefore the researchers could not determine if the decline in childhood cancer survivors is worse than the expected decline.
1. Mulder RL, Knijnenburg SL, Geskus RB, et al. glomerular function time trends in long-term survivors of childhood cancer: a longitudinal study. Cancer Epidemiol Biomarkers Prev. 2013;22:1-11.