Abstract
Impaired glomerular function is one of the health problems affecting childhood cancer survivors (CCS). It is unclear whether glomerular function deteriorates or recovers. We investigated time trends and predictors of glomerular function in CCS. We evaluated repeated observations of estimated glomerular filtration rate (GFR) and glomerular dysfunction (GFR <90 mL/min/1.73 m(2)) among adult five-year CCS treated in the EKZ/AMC between 1966 and 2003. Ifosfamide, cisplatin, carboplatin, high-dose (HD) methotrexate, HD-cyclophosphamide, radiotherapy to the kidney region, and nephrectomy (i.e., potentially nephrotoxic therapy) were investigated as predictors of glomerular function patterns over time in multivariable longitudinal analyses. At a median follow-up of 21 years after diagnosis, glomerular function was assessed in 1,122 CCS aged ≥18 years. CCS treated with potentially nephrotoxic therapy had a significantly lower GFR and higher glomerular dysfunction probability up to 35 years after cancer diagnosis compared with CCS treated without nephrotoxic therapy (P < 0.001). Especially ifosfamide, cisplatin, and nephrectomy were associated with worse glomerular function that persisted during the entire follow-up period (P < 0.001). Glomerular function deteriorated over time in all CCS (P < 0.001). CCS treated with higher doses of cisplatin seem to have a higher deterioration rate as compared with other CCS (P < 0.005). The loss in glomerular function starts early, especially for CCS treated with ifosfamide, higher doses of cisplatin, and nephrectomy, and seems to be persistent. We have an indication that CCS treated with higher doses of cisplatin experience faster decline than other CCS. As glomerular function continues to deteriorate, CCS are at risk for premature chronic renal failure.
Highlights
Because of the advances in the treatment of childhood cancer, most patients are expected to become long term survivors [1, 2]
A cisplatin by-time (P 1⁄4 0.002) and a cisplatin doseby-time interaction (P 1⁄4 0.004) was shown, indicating that cancer survivors (CCS) treated with higher doses of cisplatin showed different glomerular filtration rate (GFR) time trends as compared with CCS treated without and with lower doses of cisplatin (Fig. 2B and Supplementary Fig. S2, D–F)
The glomerular dysfunction probability increased faster in CCS treated with higher doses of cisplatin versus lower doses upto 35 years after childhood cancer diagnosis
Summary
Because of the advances in the treatment of childhood cancer, most patients are expected to become long term survivors [1, 2]. Childhood cancer survivors (CCS) are a growing group of individuals who are at risk of premature morbidity and mortality [3, 4]. Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). S.L. Knijnenburg shares joint first authorship of this article with R.L. Mulder. Impaired glomerular function is one of the health problems affecting childhood cancer survivors (CCS). It is unclear whether glomerular function deteriorates or recovers. We investigated time trends and predictors of glomerular function in CCS
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