095 - Exploratory Analysis of Kidney Injury Biomarkers in Pediatric Cancer Survivors that received Cisplatin Chemotherapy: Pilot Study
Saturday, April 26, 2025
2:30pm – 4:45pm HST
Publication Number: 95.4639
Claudia A. Mosquera Vasquez, Nationwide Children's Hospital, Columbus, OH, United States; Ahmed Zeid, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Esther Y. Pascal, Nationwide Children's Hospital, Columbus, OH, United States; Steven W. Rust, Nationwide Children's Hospital, Columbus, OH, United States; Gabriela Vasquez Martinez, Nationwide Children's Hospital, Columbus, OH, United States; Gabriel Mayoral Andrade, Nationwide Children's Hospital, Columbus, OH, United States; Randal Olshefski, Nationwide Children's Hospital, Columbus, OH, United States; Mark A. Ranalli, Nationwide Childrens Hospital, Columbus, OH, United States; Nicholas D. Yeager, Nationwide Children's Hospital, Columbus, OH, United States; Keri A. Streby, Nationwide Children's Hospital/The Ohio State University, Columbus, OH, United States; Nilay Shah, Nationwide Children's Hospital, Columbus, OH, United States; Bhuvana Setty, Nationwide Children's Hospital, Columbus, OH, United States; Margot Lazow, Nationwide Children's Hospital, Columbus, OH, United States; Diana Zepeda-Orozco, Nationwide Children's Hospital, Columbus, OH, United States
Nephrology Fellow Nationwide Children's Hospital Columbus, Ohio, United States
Background: Cisplatin chemotherapy is a risk factor for development of chronic kidney disease (CKD) and hypertension affecting around 45% of pediatric oncology patients. Glomerular hyperfiltration (GHF), has an important role in the initiation of CKD by changes in kidney hemodynamics and mechanic forces, causing podocyte and tubular damage. This phenotype has not been described in pediatric cancer survivors that received cisplatin chemotherapy. Novel urine biomarkers of tubulointerstitial injury may allow early identification of patients at risk of CKD progression in pediatric cancer survivors Objective: Identify an association of urine biomarkers of tubulointerstitial injury with kidney function decline, hypertension, and GHF. Design/Methods: This cross-sectional pilot exploratory study involved pediatric oncology survivors that completed cisplatin therapy, were in remission and off treatment in the preceding 3 months with appointments between May 2022-March 2024. We collected information retrospectively, blood pressure and laboratory results from their enrollment visit and estimated their glomerular filtration rate (eGFR) using serum creatinine CKiD U25. We measured 12 urine biomarkers of tubulointerstitial injury on multiarray plates by electrochemiluminescence using Meso Scale Discovery (MSD) and normalized them to urine creatinine measured by enzymatic assay. Normalized biomarker concentrations were log-transformed for statistical analyses. Logistic regression was employed to test for significant associations between hypertension, eGFR decline ( < 90 ml/min/1.73m2) and GHF (>130 ml/min/1.73m2) and the biomarkers’ concentrations. Results: Our cohort included 50 survivors of childhood cancer, 42% male, ages ranged between 2-31 years (median 11, IQR 7-16.25) at time of data collection. The time since end of therapy ranged between 3-143 months (median 37, IQR 18.5-93.5). Cisplatin cumulative dose median was 381.8 mg/m2 and 30% had a median single dose higher than 70 mg/m2. Four (8.1%) had eGFR decline, 17 (34.6%) GHF, and 18 (36%) with hypertension. Normalized urinary Osteoactivin concentration had a statistically significant positive association with GHF; if the concentration of urinary Osteoactivin doubles, the odds of having GHF increase by a multiplicative factor of 1.3 (CI 1.01-1.68; p 0.039).
Conclusion(s): Urinary Osteoactivin can be used to detect early kidney injury in cancer survivors after cisplatin chemotherapy with a significant association with glomerular hyperfiltration which has been proven to progress to albuminuria and CKD.
