Late-onset kidney failure in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

Abstract Background The incidence of and risk factors for late-onset kidney failure among survivors over the very long term remains understudied. Materials and methods A total of 25,530 childhood cancer survivors (median follow-up 22.3 years, interquartile range 17.4–28.8) diagnosed between 1970 and 1999, and 5045 siblings from the Childhood Cancer Survivor Study were assessed for self-reported late-onset kidney failure, defined as dialysis, renal transplantation, or death attributable to kidney disease. Piecewise exponential models evaluated associations between risk factors and the rate of late-onset kidney failure. Results A total of 206 survivors and 10 siblings developed late-onset kidney failure, a 35-year cumulative incidence of 1.7% (95% confidence interval [CI] = 1.4–1.9) and 0.2% (95% confidence interval [CI] = 0.1–0.4), respectively, corresponding to an adjusted rate ratio (RR) of 4.9 (95% CI = 2.6–9.2). High kidney dose from radiotherapy (≥15Gy; RR = 4.0, 95% CI = 2.1–7.4), exposure to high-dose anthracycline (≥250 mg/m2; RR = 1.6, 95% CI = 1.0–2.6) or any ifosfamide chemotherapy (RR = 2.6, 95% CI = 1.2–5.7), and nephrectomy (RR = 1.9, 95% CI = 1.0–3.4) were independently associated with elevated risk for late-onset kidney failure among survivors. Survivors who developed hypertension, particularly in the context of prior nephrectomy (RR = 14.4, 95% CI = 7.1–29.4 hypertension with prior nephrectomy; RR = 5.9, 95% CI = 3.3–10.5 hypertension without prior nephrectomy), or diabetes (RR = 2.2, 95%CI = 1.2–4.2) were also at elevated risk for late-onset kidney failure. Conclusions Survivors of childhood cancer are at increased risk for late-onset kidney failure. Kidney dose from radiotherapy ≥15 Gy, high-dose anthracycline, any ifosfamide, and nephrectomy were associated with increased risk of late-onset kidney failure among survivors. Successful diagnosis and management of modifiable risk factors such as diabetes and hypertension may mitigate the risk for late-onset kidney failure. The association of late-onset kidney failure with anthracycline chemotherapy represents a novel finding that warrants further study.