Chronic Kidney Disease or Hypertension After Childhood Cancer
Authors: Asaf Lebel, Rahul Chanchlani, Vedran Cockovski, Allison Dart, Adam James Fleming, Amit X. Garg, Nivethika Jeyakumar, Kirby Kim, Abhijat Kitchlu, Eric McArthur, Danielle Nash, Paul C. Nathan, Rulan S. Parekh, Rachel Pearl, Jason Pole, Raveena Ramphal, Jennifer Reid, Tal Schechter-Finkelstein, Lillian Sung, Ron Wald, Stella Wang, Peter Wong, Michael Zappitelli
Journal: JAMA Network Open (2025)

Importance Post–cancer therapy kidney outcomes, including chronic kidney disease (CKD) and hypertension, are common in childhood cancer survivors (CCS). The incidence and timing of CKD and hypertension in CCS compared with other at-risk or general populations are unclear. Objective To determine the association of childhood cancer treatment with post–cancer therapy CKD or hypertension. Design, Setting, and Participants Population-based matched cohort study of children treated for cancer between April 1993 and March 2020 in Ontario, Canada, with follow-up until March 2021. The CCS (exposed) cohort included children (≤18 years) surviving cancer. Comparator cohorts were a hospitalization cohort (children who were hospitalized) and a general pediatric population (GP) cohort (all other Ontario children). Exclusion criteria were history of previous cancer, organ transplant, CKD, dialysis, or hypertension. Matching with each of the 2 comparator cohorts was performed separately and in a 1:4 ratio by age, sex, rural vs urban status, income quintile, index year, and presence of previous hospitalization. Data were analyzed from March 2021 to August 2024. Exposure Treatment for cancer. Main Outcomes and Measures The primary outcome was the composite of CKD or hypertension, defined by administrative health care diagnosis and procedure codes. Fine and Gray subdistribution hazard modeling, accounting for competing risks (death and new cancer diagnosis or relapse) and adjusting for cardiac disease, liver disease, and diabetes, was used to determine the association of cancer treatment with outcomes. Results There were 10 182 CCS (median [IQR] age at diagnosis, 7 [3-13] years; 5529 male [54.3%]; median [IQR] follow-up time, 8 [2-15] years) matched to 40 728 hospitalization cohort patients (median [IQR] age at diagnosis, 7 [2-12] years; 5529 male [weighted percentage, 54.3%]; median [IQR] follow-up time, 11 [6-18] years) and 8849 CCS (median [IQR] age at diagnosis, 5 [2-11] years; 4825 male [54.5%]; median [IQR] follow-up time, 7 [2-14] years) matched to 35 307 GP cohort individuals (median [IQR] age at diagnosis, 6 [2-11] years; 4825 male [weighted percentage, 54.5%]; median [IQR] follow-up time, 10 [5-16] years). Most frequent cancer types were leukemia (2948 patients [29.0%]), central nervous system neoplasms (2123 patients [20.9%]), and lymphoma (1583 patients [15.5%]). During observation, cumulative incidence of CKD or hypertension was 20.85% (95% CI, 18.75%-23.02%) in the CCS cohort vs 16.47% (95% CI, 15.21%-17.77%) in the hospitalization cohort and 19.24% (95% CI, 15.99%-22.73%) in the CCS cohort vs 8.05% (95% CI, 6.76%-9.49%) in the GP cohort. CCS were at increased risk of CKD or hypertension compared with the hospitalization cohort (adjusted hazard ratio, 2.00; 95% CI, 1.86-2.14; P &amp;amp;lt; .001) and the GP cohort (adjusted hazard ratio, 4.71; 95% CI, 4.27-5.19; P &amp;amp;lt; .001). Conclusions and Relevance In this population-based study, CCS were at increased risk for CKD and hypertension, which are associated with mortality, suggesting that early detection and treatment of these conditions in CCS may decrease late complications and mortality.