Effects of induction-phase acute kidney injury and age at diagnosis on chronic kidney disease in pediatric acute lymphoblastic leukemia: a time-to-event cohort study.
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BACKGROUND: The survival rate of pediatric acute lymphoblastic leukemia (ALL) currently exceeds 90% in high-income settings, shifting the focus to its long-term effects. Kidney injury, acute kidney injury (AKI), and chronic kidney disease (CKD) are increasingly recognized associated conditions; however, the determinants of CKD in pediatric ALL remain poorly defined. PURPOSE: To quantify the burden of AKI during induction and CKD in children with ALL, estimate CKD-free survival, and identify clinical predictors of CKD. METHODS: This retrospective cohort at a single university-affiliated tertiary center included patients aged 2-18 years with ALL who completed ≥3 months of follow-up. AKI was classified by Kidney Disease: Improving Global Outcomes serum-creatinine criteria, while CKD was defined as a glomerular filtration rate <90 mL/min/1.73 m2 for ≥3 months. CKD-free survival was estimated using the Kaplan-Meier method. Associations with time to CKD were assessed using the Cox proportional hazards model. RESULTS: Of 113 children (median age, 5.6; interquartile range [IQR], 3.8-9.4 years), AKI occurred during induction in 49 (43.4%). Leukemic kidney infiltration (LKI) was more frequently noted in patients with versus without AKI (P=0.01). Over 644 patient-years of follow-up (median, 5.1; IQR, 2.9-8.3 years), 15 (13.3%) developed CKD (stage 2 [n=12], stage 3 [n=3]). The 1-, 3-, and 5-year CKD-free survival rates were 99.1%, 95.3%, and 94.1%, respectively. In multivariate models, age was independently associated with CKD (adjusted hazard ratio [aHR], 1.28 per year; 95% confidence interval [CI], 1.04-1.57; P=0.02), whereas the incidence of LKI did not reach significance (aHR, 2.93; 95% CI, 0.87-9.89; P=0.08). CONCLUSION: AKI commonly developed during induction. An older age at diagnosis was the principal independent predictor of CKD development. The age effect demonstrated a linear risk gradient rather than a conventional dichotomous ≥10-year threshold. A LKI was associated with AKI and suggestive of subsequent CKD. These results suggest that older children may benefit from intensive kidney surveillance and supportive care. Multicenter prospective studies are warranted to refine the prevention strategies.