St. Jude Children's Research Hospital, Memphis, TN
Daniel M. Green , Mingjuan Wang , Matthew J. Krasin , Deokumar Srivastava , Carrie R. Howell , Dennis W. Jay , Kirsten K. Ness , William Greene , Jennifer Q. Lanctot , Kyla C. Shelton , Andrew M. Davidoff , Matthew J. Ehrhardt , Daniel A. Mulrooney , Leslie L. Robison , Melissa M. Hudson
Background: We assessed renal function in a large, clinically assessed cohort of childhood cancer survivors. Methods: Creatinine and qualitative urine protein was measured in 2753 survivors (>10 years (years) post-diagnosis, age ≥18 years). Renal function was graded per the Kidney Disease International Global Outcomes 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD). Multivariable logistic regression was used to estimate associations between demographics, treatment exposures, and CKD (grades 1-5 and 3-5). Radiation treatment was expressed as percentage of total kidney volume treated with 5 (V5), 10 (V10), 15 (V15) and 20 (V20) Gray. Results: Among 2753 survivors, 48.7% were female and 82.5% non-Hispanic white. Median age at diagnosis - 7.3 years (interquartile range [IQR]=3.3-13.2), median age at evaluation - 31.4 years (IQR=25.8-37.8), and median time from diagnosis to evaluation - 23.2 years (IQR=17.6-29.7). Prevalence of grades 1-5 and 3-5 CKD was 7.4% and 2.1%, respectively (grade 1=113, grade 2=30, grade 3=44, grade 4=5, and grade 5=8). Individual and cumulative aminoglycoside doses and treatment with high-dose methotrexate were not associated with CKD (data not shown). Cumulative number of doses of ambisome/abelcet and of amphotericin B were significant risk factors for grades 1-5 and grades 3-5 CKD in models for V15 and V20 (data not shown). The multivariable results for V10 are shown in the Table. Conclusions: In addition to nephrotoxic antineoplastic and supportive care therapy, race, ethnicity, and body composition contribute to risk of CKD in long-term survivors. These novel results inform late effects reduction strategies for future treatment protocols and identify survivors at highest risk for CKD.
Grades 1 – 5 CKD | Grades 3 – 5 CKD | |||
---|---|---|---|---|
Odds ratio (95%CI) | p-value | Odds ratio (95% CI) | p-value | |
Other vs Non-Hispanic white | 1.98 (1.39 to 2.81) | <0.001 | * | * |
Age at renal function evaluation (per yr) | 1.04 (1.02 to 1.06) | <0.001 | 1.10 (1.06 to 1.14) | <0.001 |
BMI ≥ 30 vs ≥ 13 to < 25 | 1.72 (1.19 to 2.48) | 0.004 | * | * |
Nephrectomy (yes) | 2.07 (1.24 to 3.45) | 0.005 | * | * |
Ifosfamide (per 1000 mg/m2) | 1.01 (1.00 to 1.02) | 0.03 | 1.03 (1.01 to 1.05) | < 0.001 |
Cis-platinum (per 100 mg/m2) | 1.16 (1.05 to 1.28) | 0.004 | 1.41 (1.24 to 1.60) | <0.001 |
Carboplatinum (per 100 mg/m2) | * | * | 1.03 (1.00 to 1.06) | 0.035 |
Amphotericin B (per dose) | 1.02 (1.00 to 1.04) | 0.048 | * | * |
V10 (per 1%) | 1.01 (1.00 to 1.01) | < 0.001 | 1.02 (1.02 to 1.03) | <0.001 |
* did not meet criteria for inclusion in the model
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