Kidney function trajectories in pediatric acute lymphoblastic leukemia.

Abstract

e18513 Background: Acute kidney injury (AKI) is common in pediatric acute lymphoblastic leukemia (ALL) and can increase the risk of developing chronic kidney disease (CKD). However, AKI phenotypes vary widely in severity, duration, and number of episodes that may be characterized as patterns in estimated glomerular filtration rate (eGFR) trajectories. Distinct eGFR trajectories during therapy for ALL may indicate long-term CKD risk in pediatric ALL survivors. To our knowledge, eGFR trajectories have not been described in the pediatric ALL population. Objective: To identify groups based on eGFR trajectory during ALL therapy and to evaluate characteristics associated with declining eGFR groups. Methods: Electronic health record data were retrospectively collected from pediatric patients treated for de novo B- and T-ALL at Children’s Hospital of Philadelphia (2011-2015), Children’s Healthcare of Atlanta (2010-2018), and Texas Children’s Hospital (2011-2014), three large cancer centers in the Leukemia Electronic Abstraction of Records Network (LEARN). Patients with infant ALL were excluded. Patients were followed from the time of first chemotherapy course in LEARN through upfront chemotherapy completion, death, relapse, conditioning for stem cell transplant, or transfer of care, whichever came first. Latent class mixed models were used to determine course-level eGFR trajectory groups. Bivariate tests and multinomial logistic regressions were used to explore the association of covariates with specific trajectory groups. Results: Cohort characteristics (n=884) included: median (interquartile range) age 5.7 years (3.4-11.4), 56% male, median baseline eGFR 107.6 mL/min/1.73m 2 (89.8-126.8), 2% with Trisomy 21 (T21), and 54% with National Cancer Institute standard risk leukemia. Between 3-4 eGFR trajectory groups were identified in each course. All courses had stable eGFR trajectory groups distinguished by their course-specific baseline eGFR. Induction and Interim Maintenance-1 had additional groups with initial eGFR decline and recovery. Consolidation and Delayed Intensification courses had groups with eGFR decline. Bivariate analyses indicated that declining eGFR trajectory groups were significantly associated with lower course-specific baseline eGFR, AKI during the course, and T21; median number of eGFR values were not consistently associated with specific trajectory groups across courses. Multinomial logistic regression showed that those with higher baseline eGFR had increased odds of being in stable eGFR trajectory groups across all courses. Prior AKI was associated with increased odds of being in a lower eGFR trajectory group in Interim Maintenance-2. Conclusions: Pediatric patients with ALL have distinct eGFR trajectories during therapy. Patients with lower baseline eGFR, AKI, and a diagnosis of T21 may be at highest risk of eGFR decline during therapy and may benefit from increased screening for CKD.