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PLoS One. 2014 Oct 24;9(10):e110865. doi: 10.1371/journal.pone.0110865. eCollection 2014.

Validation of cell-cycle arrest biomarkers for acute kidney injury after pediatric cardiac surgery.

Author information

1
Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
2
Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
3
Department of Pediatric Cardiology, University of Münster, Münster, Germany.
4
Department of Pediatric Heart Surgery, University of Münster, Münster, Germany.

Abstract

BACKGROUND:

The lack of early biomarkers for acute kidney injury (AKI) seriously inhibits the initiation of preventive and therapeutic measures for this syndrome in a timely manner. We tested the hypothesis that insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, function as early biomarkers for AKI after congenital heart surgery with cardiopulmonary bypass (CPB).

METHODS:

We prospectively studied 51 children undergoing cardiac surgery with CPB. Serial urine samples were analyzed for [TIMP-2]•[IGFBP7]. The primary outcome measure was AKI defined by the pRIFLE criteria within 72 hours after surgery.

RESULTS:

12 children (24%) developed AKI within 1.67 (SE 0.3) days after surgery. Children who developed AKI after cardiac surgery had a significant higher urinary [TIMP-2]•[IGFBP7] as early as 4 h after the procedure, compared to children who did not develop AKI (mean of 1.93 ((ng/ml)²/1000) (SE 0.4) vs 0.47 ((ng/ml)²/1000) (SE 0.1), respectively; p<0.05). Urinary [TIMP-2]•[IGFBP7] 4 hours following surgery demonstrated an area under the receiver-operating characteristic curve of 0.85. Sensitivity was 0.83, and specificity was 0.77 for a cutoff value of 0.70 ((ng/ml)²/1000).

CONCLUSIONS:

Urinary [TIMP-2]•[IGFBP7] represent sensitive, specific, and highly predictive early biomarkers for AKI after surgery for congenital heart disease.

TRIAL REGISTRATION:

www.germanctr.de/, DRKS00005062.

PMID:
25343505
PMCID:
PMC4208780
DOI:
10.1371/journal.pone.0110865
[Indexed for MEDLINE]
Free PMC Article

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