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Abstract: FR-PO1080

Cell Cycle Arrest Biomarkers to Diagnose Pediatric AKI due to Cisplatin

Session Information

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.