Nephrotoxicity and kidney outcomes in pediatric oncology patients

Abstract

Background Acute kidney injury (AKI) is a serious complication during pediatric cancer treatment. Nephrotoxic medication may increase the risk of developing AKI, which may necessitate modifications to standard treatment and may also increase the risk of chronic kidney disease (CKD). This study investigates the incidence of AKI, the impact of nephrotoxic medications and the association between AKI and the development of CKD. Methods In this retrospective national cohort study, we analyzed 1525 pediatric cancer patients treated at the Princess Máxima Center between 2015 and 2021. AKI was classified using KDIGO criteria based on serum creatinine. The effect of nephrotoxic medications and other risk factors on AKI incidence and progression was assessed by using a cause specific hazard regression model. The cumulative incidence of AKI was estimated with a competing risk model with death as competing event. The effect of risk factors on CKD, defined as an eGFR <90 ml/min/1.73 m² 1 year after cancer treatment, was evaluated with a logistic regression. Results We included 1525 patients, 37% experienced AKI. A competing risk model identified treatment with ifosfamide, amphotericin B, acyclovir, and busulfan as strong, independent risk factors for a first episode of AKI. Older age was also associated with an increased risk of AKI. At 1-year follow-up (n = 1159), 13.6% had CKD (eGFR <90 ml/min/1.73 m²), and 2.8% had an eGFR <60. AKI (occurred during treatment) was the strongest predictor of CKD: A single AKI episode increased the risk 2.6-fold, while more episodes increased it nearly 16-fold. Nephrectomy was also identified as independent risk factors for CKD. Conclusion Acute kidney injury (AKI) is common in children with cancer and is strongly associated with an increased risk of chronic kidney disease (CKD). Awareness is crucial for high-risk patients, particularly those receiving nephrotoxic medications, with a history of multiple AKI episodes or a prior nephrectomy. Comprehensive monitoring strategies should be implemented at diagnosis, during therapy, and during the post-Treatment period to enable early detection and timely intervention, ultimately reducing the risk of AKI and its progression to CKD.