Research Student The Hospital for Sick Children Brampton, Ontario, Canada
Background: Children treated with cisplatin or who have been hospitalized with Acute Kidney Injury (AKI) have a high risk of developing long-term Chronic Kidney Disease (CKD) and Hypertension (HTN). Acute kidney tissue damage, including endothelial injury, can lead to kidney tissue fibrosis, which may lead to activation of the Renin Angiotensin Aldosterone System (RAAS). We hypothesize that RAAS may be involved in the pathophysiology of AKI to CKD or HTN development and that RAAS biomarkers predict CKD or HTN after AKI. There is little data on the role of RAAS in long-term AKI outcomes.
Objective: Investigate the extent to which urine markers of RAAS activity are predictive of, or associated with, signs of CKD and HTN in children who are: 1. 1 year & 3 years post-cisplatin (post- CisP) treatment. 2. 5 & 11 years post-pediatric Intensive Care Unit (PICU) discharge.
Design/Methods: Data and samples from two prospective cohort studies were used: A) 12-centre study of children during and until 3-years post-CisP. Exclusions: Kidney transplant, glomerular filtration rate (GFR) < 30mL/min/1.73m2 pre-CisP. B) Single-centre study of patients 5 & 11 years post- PICU discharge. Exclusions: end-stage renal disease pre-PICU. Study designs shown in Fig 2 Excluded from analyses: unavailable urine samples at timepoints; missing kidney data at 3-, 12-, or 36-month post-CisP or at 5- or 11-years post PICU discharge.(fig 1) Exposures: Urine Angiotensinogen (uAGT) level, Angiotensin Converting Enzyme (ACE) and ACE2 activities (selected by literature review). Outcomes: CKD (high albumin or low GFR for age); Elevated BP or worse. Analysis for this poster: Population characteristics for the post CisP cohort described through Chi- squared, Wilcox Rank-sum, and Fisher’s Exact tests on Stata. Future planned analyses both cohorts: Future analyses will include univariable and multivariable modelling, including Chi-squared, Wilcox Rank-sum, and Fisher’s Exact tests. Receiver Operating Characteristic (ROC) Curves and Area Under the Curve (AUC) of Sensitivity vs. 1 – Specificity (fig 2) will be used for each biomarker both predictively and cross- sectionally.(fig 3)
Results: N/A
Conclusion(s): Given the prevalence of CKD and HTN during follow-up, there is high incentive to predict these outcomes because they are associated with cardiovascular risk and are treatable. The role of RAAS is important to evaluate because RAAS inhibitors may be used to treat both CKD or HTN.
