Childhood cancer survivors had an increased risk of chronic kidney disease (CKD) and hypertension, a Canadian population-based matched cohort study suggested.

Over up to 27 years of observation, the cumulative incidence of CKD or hypertension was 20.85% among childhood cancer survivors compared with 16.47% in a cohort of kids who were hospitalized, and 19.24% among another cohort of childhood cancer survivors compared with 8.05% in a general pediatric cohort, reported Michael Zappitelli, MD, MSc, of the Hospital for Sick Children in Toronto, and colleagues.

Childhood cancer survivors had a twofold higher adjusted risk of CKD or hypertension versus the hospitalized cohort (adjusted HR 2.00, 95% CI 1.86-2.14, P<0.001) and a fourfold higher adjusted risk versus the general population cohort (aHR 4.71, 95% CI 4.27-5.19, P<0.001), they noted in JAMA Network Openopens in a new tab or window.

The magnitude of these associations was largest when follow-up time was under 1 year (aHR 6.45, 95% CI 5.78-7.19, vs the hospitalization cohort and aHR 23.57, 95% CI 19.57-28.39, vs the general population cohort).

“Outcomes became evident within the first year after cancer treatment,” Zappitelli and colleagues noted. “These results strengthen the hypothesis that [childhood cancer survivors] require monitoring for blood pressure and kidney health soon after cancer treatment is complete and ongoing into adulthood.”

“Improved treatments and survival for childhood cancer have come with a cost of adverse cancer treatment effects; more than 99% of childhood cancer survivors have chronic health problemsopens in a new tab or window by age 50 years,” the authors explained, noting that long-term kidney outcomes, such as CKD and hypertension, are common in this population.

However, they pointed out that the incidence and timing of CKD and hypertension in childhood cancer survivors compared with kids hospitalized for other reasons or the general population are unclear, and studies on kidney outcomes in childhood cancer survivors “have been relatively small or without comparator cohorts, which are acknowledged as major barriers to quantifying long-term kidney health risk.”

“This lack of robust evidence may partially explain why CCS [childhood cancer survivor] kidney health follow-up guidelines are vague and nonactionable,” they added. “Administrative healthcare data research may help overcome this issue and provide evidence needed to improve follow-up guidelines.”

For this study, Zappitelli and colleagues included children treated for cancer between April 1993 and March 2020 in Ontario, Canada, with follow-up until March 2021. Matching with the hospitalization and general pediatric comparator cohorts was performed separately and in a 1:4 ratio by age, sex, rural versus urban status, income quintile, index year, and presence of previous hospitalization.

They compared 10,182 childhood cancer survivors to 40,728 children in the hospitalization cohort (median age at diagnosis 7 years, 54.3% boys for both groups), and 8,849 childhood cancer survivors to 35,307 children in the general population cohort (median age 5 and 6 years, respectively, 54.5% boys).

The most frequent cancer types were leukemia (29%), central nervous system neoplasms (20.9%), and lymphoma (15.5%). About half of childhood cancer survivors included in the study received well-known nephrotoxic chemotherapies.

The incidences of outcomes were likely underestimated because diagnosing pediatric CKD and hypertension using administrative data is “very specific but not sensitive,” Zappitelli and colleagues noted.

Additionally, they were unable to differentiate CKD manifestations and stages and adjust for other potential risk factors like obesity, family history, smoking, and race and ethnicity.

Moreover, they were not able to include acute kidney injury (AKI) during cancer therapy as a variable in the analysis. “This will prove challenging because AKI can occur multiple times over a prolonged period of time for [childhood cancer survivors], as opposed to a single AKI episode occurring during a hospitalization in most hospitalized children,” they wrote.