Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury after Pediatric Cardiac Surgery

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]N[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]N[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 [TIMP2]N[IGFBP7] 4 hours following surgery demonstrated an area under the receiver-operating characteristic curve of 0.85.