Kidney Function after Treatment for Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study

Background Survivors of childhood cancer may be at increased risk for treatment-related kidney dysfunction. Although associations with acute kidney toxicity are well described, evidence informing late kidney sequelae is less robust. Methods To define the prevalence of and risk factors for impaired kidney function among adult survivors of childhood cancer who had been diagnosed ?10 years earlier, we evaluated kidney function (eGFR and proteinuria). We abstracted information from medical records about exposure to chemotherapeutic agents, surgery, and radiation treatment and evaluated the latter as the percentage of the total kidney volume treated with ?5 Gy (V5), ?10 Gy (V10), ?15 Gy (V15), and ?20 Gy (V20). We also used multivariable logistic regression models to assess demographic and clinical factors associated with impaired kidney function and Elastic Net to perform model selection for outcomes of kidney function. Results Of the 2753 survivors, 51.3% were men, and 82.5% were non-Hispanic White. Median age at diagnosis was 7.3 years (interquartile range [IQR], 3.3?13.2), and mean age was 31.4 years (IQR, 25.8?37.8) at evaluation. Time from diagnosis was 23.2 years (IQR, 17.6?29.7). Approximately 2.1% had stages 3?5 CKD. Older age at evaluation; grade ?2 hypertension; increasing cumulative dose of ifosfamide, cisplatin, or carboplatin; treatment ever with a calcineurin inhibitor; and volume of kidney irradiated to ?5 or ?10 Gy increased the odds for stages 3?5 CKD. Nephrectomy was significantly associated with stages 3?5 CKD in models for V15 or V20. Conclusions We found that 2.1% of our cohort of childhood cancer survivors had stages 3?5 CKD. These data may inform screening guidelines and new protocol development. Significance Statement Although associations of treatment for childhood cancer with acute kidney toxicity are well described, evidence informing late kidney sequelae is less robust. The authors evaluated the prevalence of and factors associated with increased odds for kidney impairment in a large cohort of adult survivors of childhood cancer diagnosed ?10 years earlier. About 2.1% had stages 3?5 CKD. Factors associated with stages 3?5 CKD included treatment ever with a calcineurin inhibitor, increasing cumulative dose of certain chemotherapy agents, increasing volume of kidney irradiated to ?5 or ?10 Gy, nephrectomy (in patients who received radiation to the kidney) in models for higher?radiation therapy dose-volume exposures, and others. These findings may inform surveillance guidelines for survivors of childhood cancer and the design of future treatment regimens.

Automated summary

The study evaluated the prevalence of impaired kidney function and identified factors associated with increased odds for kidney impairment in adult survivors of childhood cancer diagnosed ?10 years earlier. About 2.1% of survivors had stages 3?5 CKD, with factors such as treatment with certain chemotherapy agents and kidney irradiation volume contributing to the risk.