Bryan V Dieffenbach1, Qi Liu2, Andrew J Murphy3, Deborah R Stein4, Natalie Wu5, Arin L Madenci6, Wendy M Leisenring5, Nina S Kadan-Lottick7, Emily R Christison-Lagay8, Robert E Goldsby9, Rebecca M Howell10, Susan A Smith10, Kevin C Oeffinger11, Yutaka Yasui12, Gregory T Armstrong12, Christopher B Weldon13, Eric J Chow5, Brent R Weil13. 1. Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. Electronic address: bdieffenbach@bwh.harvard.edu. 2. School of Public Health, University of Alberta, Edmonton, Alberta, Canada. 3. Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN, USA. 4. Division of Nephrology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. 5. Clinical Research and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 6. Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. 7. Section of Pediatric Hematology-Oncology, Yale University and Yale Cancer Center, New Haven, CT, USA. 8. Division of Pediatric Surgery, Department of General Surgery, Yale School of Medicine, New Haven, USA. 9. Division of Oncology, Department of Pediatrics, UCSF Benioff Children's Hospital, San Francisco, CA, USA. 10. Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 11. Department of Medicine, Duke University School of Medicine, Durham, NC, USA. 12. Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. 13. Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
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.
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.
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