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Abstract: FR-PO1079

Cell Cycle Arrest Biomarkers and Kidney Injury Molecule 1 (KIM-1) in Pediatric Aminoglycoside-Induced AKI

Session Information

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Chui, Hayton, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Cockovski, Vedran, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Devarajan, Prasad, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Goldstein, Stuart, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Ma, Qing, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Zappitelli, Michael, The Hospital for Sick Children, Toronto, Ontario, Canada
Background

AKI is common in children treated with aminoglycosides (AG). We evaluated urine KIM1 and cell cycle arrest biomarkers (tissue inhibitor of metalloproteinase 2 [TIMP2]; insulin-like growth factor-binding protein 7 [IGFBP7]) for AG-AKI diagnosis.

Methods

Nested-case control study from a prospective 2-center (Montreal, Cincinnati) cohort (non-critically ill children starting AG's; 3 months-18 years old; no known kidney condition; AG treatment ≥3 days; recruited within 48 hours of AG start; ≥1 SCr’s/5 AG days). Urine was collected daily, measured for KIM1 (pg/ml), TIMP2 (ng/ml) and IGFBP7 (ng/ml) (expressed as TIMP2*IGFBP7). AKI: KDIGO SCr definition. Non-AKI vs. AKI biomarkers were compared on a) AG treatment day 2 and 3, and b) 3, 2 and 1 day before and the day of AKI onset (Mann-Whitney). Area under the receiver operating characteristic curve (AUC, 95% CI) to detect AKI was calculated.

Results

104 AG episodes (48% male, age 8.0 ± 4.9 years; AG treatment days 8.1 ± 7.7); 41% developed AKI. Results in Table: KIM1 ~3-fold higher in AKI vs. non-AKI, on day of AKI onset (AUC 0.87 [0.72-1.00]); no statistically significant AKI association on other days. TIMP2*IGFBP7 ~6-fold higher in AKI vs. non-AKI on AG treatment day 2 (AUC 0.72 [0.57-0.87]); on day of AKI onset (AUC 0.75 [0.54-0.97]) to detect AKI. Results not in Table: KIM1 combined with TIMP2*IGFBP7 on the day of AKI onset detected AKI with AUC 0.90 (0.78 – 1.00, p<0.05).

Conclusion

KIM1 and TIMP2*IGFBP7 are diagnostic of AG-AKI only the day of AKI onset. Future research should validate our findings and investigate these biomarkers to predict AKI severity and recovery.

Table: Urinary KIM1 and TIMP2*IGFBP7 concentrations by AKI status, with AUC to detect AKI during AG treatment
Bolded value: AUC Confidence Interval >0.5
*p-value <0.05 for comparison between AKI vs. Non-AKI

Funding

  • Government Support - Non-U.S.