Green Daniel M, Wang Mingjuan, Krasin Matthew, Srivastava DeoKumar, Onder Songul, Jay Dennis W, Ness Kirsten K, Greene William, Lanctot Jennifer Q, Shelton Kyla C, Zhu Liang, Mulrooney Daniel A, Ehrhardt Matthew J, Davidoff Andrew M, Robison Leslie L, Hudson Melissa M
Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
J Am Soc Nephrol. 2021 Apr;32(4):983-993. doi: 10.1681/ASN.2020060849. Epub 2021 Mar 2.
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.
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.
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.
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.
儿童癌症幸存者出现与治疗相关的肾功能障碍的风险可能会增加。虽然与急性肾毒性的关联已有充分描述，但关于晚期肾脏后遗症的证据尚不充分。
为了确定10年多以前被诊断为儿童癌症的成年幸存者中肾功能受损的患病率及危险因素，我们评估了肾功能（估算肾小球滤过率[eGFR]和蛋白尿）。我们从医疗记录中提取了有关化疗药物暴露、手术和放射治疗的信息，并将放射治疗评估为接受≥5 Gy（V5）、≥10 Gy（V10）、≥15 Gy（V15）和≥20 Gy（V20）照射的肾脏总体积的百分比。我们还使用多变量逻辑回归模型评估与肾功能受损相关的人口统计学和临床因素，并使用弹性网络法对肾功能结局进行模型选择。
在2753名幸存者中，51.3%为男性，82.5%为非西班牙裔白人。诊断时的中位年龄为7.3岁（四分位间距[IQR]，3.3 - 13.2），评估时的平均年龄为31.4岁（IQR，25.8 - 37.8）。从诊断到评估的时间为23.2年（IQR，17.6 - 29.7）。约2.1%患有3 - 5期慢性肾脏病（CKD）。评估时年龄较大；高血压≥2级；异环磷酰胺、顺铂或卡铂的累积剂量增加；曾使用钙调神经磷酸酶抑制剂治疗；以及接受≥5或≥10 Gy照射的肾脏体积增加，均会增加3 - 5期CKD的几率。在V = 15或V = 20的模型中，肾切除术与3 - 5期CKD显著相关。
我们发现，在我们的儿童癌症幸存者队列中，2.1%患有3 - 5期CKD。这些数据可为筛查指南和新方案的制定提供参考。
