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

Melanie Meersch,Christoph Schmidt,Dirk Stege,Edward Malec,Jan Rossaint,Katarzyna Januszewska,Hugo Van Aken,Dennis Görlich,Alexander Zarbock,Daqing Ma

doi:10.1371/journal.pone.0110865

Melanie Meersch, Christoph Schmidt + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0110865

Copy DOI

Journal: PloS one	Publication Date: Oct 24, 2014
Citations: 134	License type: CC BY 4.0

Affiliation: University of Münster, University Hospital Münster

Abstract

BackgroundThe 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).MethodsWe 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.Results12 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).ConclusionsUrinary [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

Highlights

Acute kidney injury (AKI) is a common complication of pediatric cardiac surgery and negatively impacts short- and longterm outcomes [1,2,3]
In a recent adult study, we showed that tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are elevated 24 to 48 hours before the clinical diagnosis of cardiac surgery-associated acute kidney injury (AKI) becomes apparent [11]
To show the benefit of the extended model we report the result of the likelihood ratio test between the two models

Summary

Introduction

Acute kidney injury (AKI) is a common complication of pediatric cardiac surgery and negatively impacts short- and longterm outcomes [1,2,3]. Serum creatinine (SCr), the traditional marker of renal function, does not rise appreciably before a 50% loss in glomerular filtration rate (GFR) had occurred. The other traditional marker of renal function, urine output, has a low specificity after cardiac surgery, because it is influenced by several factors. 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)

Objectives

Methods

Results

Conclusion