Abstract: FR-PO1080
Cell Cycle Arrest Biomarkers to Diagnose Pediatric AKI due to Cisplatin
Session Information
- Pediatric Hypertension, AKI, Urologic Disorders
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1700 Pediatric Nephrology
Authors
- Chui, Hayton, The Hospital for Sick Children, Toronto, Ontario, Canada
- McMahon, Kelly, McGill University Health Centre, Montreal, Quebec, Canada
- Yordanova, Mariya, Montreal Children's Hospital, Montreal, Quebec, Canada
- Huynh, Louis, Queen's University School of Medicine, Kingston, Ontario, Canada
- Crépeau-Hubert, Frédérik, McGill University, Montreal, Quebec, Canada
- Lee, Jasmine, The Hospital for Sick Children, Toronto, Ontario, Canada
- Blydt-Hansen, Tom D., University of British Columbia, Vancouver, British Columbia, Canada
- Pinsk, Maury N., University of Manitoba, Winnipeg, Manitoba, Canada
- Mammen, Cherry, British Columbia Children's Hospital, Vancouver, British Columbia, Canada
- Rassekh, Shahrad Rod, British Columbia Children's Hospital, Vancouver, British Columbia, Canada
- Schultz, Kirk Raymond, British Columbia Children's Hospital, Vancouver, British Columbia, Canada
- Devarajan, Prasad, Cincinnati Children's Hospital, Cincinnati, Ohio, United States
- Ma, Qing, Cincinnati Children's Hospital, Cincinnati, Ohio, United States
- Zappitelli, Michael, The Hospital for Sick Children, Toronto, Ontario, Canada
Background
Cisplatin (CisP) causes AKI and electrolyte abnormalities. Urine tissue inhibitor of metalloproteinase 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) may be early AKI biomarkers.
Methods
12-site, prospective cohort study of children treated for cancer with >=1 CisP cycle. Excluded: >18 years, kidney transplant, GFR<30ml/min/1.73m2. Blood and urine collected at pre and 24-hrs post CisP during 1st or 2nd CisP cycle (Early Visit [EV]) and during 2nd to last or last CisP cycle (Late Visit[LV]). Urine measured for TIMP2(ng/ml), IGFBP7(ng/ml) (expressed as TIMP2*IGFBP7). AKI Outcomes: 1) KDIGO SCr definition; 2) Combined KDIGO SCr and electrolyte abnormality-based definition (from National Cancer Institute [NCI] criteria) - KDIGO+NCI. AKI vs. non-AKI TIMP2*IGFBP7 were compared pre and post CisP (Mann Whitney); within-subject pre vs. post CisP were compared (Wilcoxon signed-rank). Area under the curve (AUC, 95% CI) to detect AKI was calculated. Clinical model comparison for AKI prediction: neuroblastoma (yes/no) + age<3 years; assessed added benefit of TIMP2*IGFBP7 to increase AUC (DeLong).
Results
n=159, median [IQR] age 5.4 [9.4] years, 50% male. KDIGO AKI: EV 30%; LV 16%. KDIGO+NCI AKI: EV 20%; LV 11%. Table: AKI vs. non-AKI: EV Pre TIMP2*IGFBP7 is 5-7 fold lower in AKI, p<0.05; LV Post TIMP2*IGFBP7 is 4-6 fold higher in AKI, p<0.05. Non-AKI pre vs. post: TIMP2*IGFBP7 drops after CisP, p<0.05. Highest AUC: LV post (0.70-0.73). Clinical model: AUC 0.70 (0.58-0.81); addition of TIMP2*IGFBP7 increased LV Post AUC (0.77 [0.66-0.87]), p<0.05.
Conclusion
TIMP2*IGFBP7 is a modest predictor of CisP-AKI. Drop in TIMP2*IGFBP7 might be protective of CisP induced injury, but results must be validated in another cohort.
Table: Urinary TIMP2*IGFBP7 ((ng/ml)2/1000) excretion pre and post Cisplatin with AUC's to diagnose post-Cisplatin AKI
Bolded values: AUC 95% CI >0.5
*Indicates p<0.05, comparing AKI vs. non-AKI (Mann-Whitney U)
#Indicates p<0.05, comparing pre- vs. post-biomarker concentrations (Wilcoxon signed-rank)
Funding
- Government Support - Non-U.S.