Childhood Cancer and the Risk of ESKD

Ronit Calderon-Margalit; Oren Pleniceanu; Dorit Tzur; Michal Stern-Zimmer; Arnon Afek; Tomer Erlich; Guy Verhovsky; Lital Keinan-Boker; Karl Skorecki; Gilad Twig; Asaf Vivante

doi:10.1681/ASN.2020071002

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Significance Statement

The number of pediatric cancer survivors has steadily increased in recent decades because of higher incidence rates of cancer and improved treatments. Although children with cancer are exposed to various factors that might compromise kidney function, whether childhood cancer is associated with an increased risk of ESKD at adulthood is unknown. In this population-based, retrospective cohort study in Israel comprising 1,468,600 participants, the authors found that individuals with a history of childhood cancer had a risk of ESKD during a follow-up period of 30 years that was substantially elevated compared with that of individuals who were not childhood cancer survivors. These findings demonstrate a link between experiencing cancer during childhood and adverse renal outcome during adulthood, suggesting the need for closer and longer nephrological follow-up of survivors of childhood cancer.

Abstract

Background Increasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors’ exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease.

Methods To assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997. After obtaining detailed histories, we divided the cohort into three groups: participants without a history of tumors, those with a history of a benign tumor (nonmalignant tumor with functional impairment), and those with a history of malignancy (excluding kidney cancer). This database was linked to the Israeli ESKD registry to identify incident ESKD cases. We used Cox proportional hazards models to estimate the hazard ratio (HR) of ESKD.

Results Of the 1,468,600 participants in the cohort, 1,444,345 had no history of tumors, 23,282 had a history of a benign tumor, and 973 had a history of malignancy. During a mean follow-up of 30.3 years, 2416 (0.2%) participants without a history of tumors developed ESKD. Although a history of benign tumors was not associated with an increased ESKD risk, participants with a history of malignancy exhibited a substantially elevated risk for ESKD compared with participants lacking a history of tumors, after controlling for age, sex, enrollment period, and paternal origin (adjusted HR, 3.2; 95% confidence interval, 1.3 to 7.7).

Conclusions Childhood cancer is associated with an increased risk for ESKD, suggesting the need for tighter and longer nephrological follow-up.

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