ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

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.