Long-Term Kidney Outcomes of Pediatric Acute Lymphoblastic Leukemia Survivors

Background: Hypertension (HTN) and chronic kidney disease (CKD) have been described in pediatric cancer survivors but renal outcomes following childhood acute lymphoblastic leukemia (cALL), the most frequent pediatric cancer, remain poorly defined. We aimed to determine the prevalence of abnormal estimated glomerular filtration rate (eGFR) and HTN among cALL survivors in the short- and long-term and assess potential associations with clinical characteristics prior to end of treatment. Methods: This is a retrospective cohort study of 237 cALL survivors with no prior kidney disease. Clinical, imaging, and laboratory data were documented from cALL diagnosis to end of treatment (1987-2010) and at study follow-up (2013-2015). Logistic regression models were used to examine relationships between clinical characteristics and kidney outcomes. Results: 49.8% of the cohort were males and median age at diagnosis was 4.8 (IQR = 3.0-9.8) years. By end of treatment, HTN and acute kidney injury (AKI) were diagnosed in 15.3% and 34.2% of patients respectively. Stage 1 AKI represented 77.8% of all AKI episodes. Initial ultrasound findings suggestive of leukemic kidney infiltration (LKI) and tumor lysis syndrome (TLS) were associated with higher AKI risk. HTN risk was higher among children younger than 5 years old (OR 2.3; 95% CI 1.1-4.8), those with LKI (3.5; 1.5-7.9), and who had AKI (2.5; 1.2-5.2). Median length of follow-up was 15.0 (11.6-19.7) years, with median age of 21.4 (16.8-25.9) years old. High blood pressure values suggesting HTN were recorded in 11.5% of patients. Mean eGFR was 100.3±15.7 ml/min/1.73m2, with no difference between patients who had previous severe AKI episodes versus not. 27.1% of the cohort met criteria for stage 2 CKD (eGFR < 90 ml/min/1.73 m2). CKD at long-term follow-up was not associated with number of AKI episodes, AKI severity, nor HTN prior to end of treatment. Prior severe AKI episodes were associated with high blood pressure at follow-up (5.1; 1.7-15.2). Conclusions: Attention may be warranted for patients with ultrasound findings suggestive of LKI and TLS prior to end of treatment. cALL survivors who had severe AKI would benefit from long-term blood pressure monitoring. All cALL survivors should have their kidney function monitored as over 1 in 4 had stage 2 CKD by early adulthood, regardless of previous AKI or HTN diagnoses.

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