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Elevated Levels of Urinary Biomarkers TIMP-2 and IGFBP-7 Predict Acute Kidney Injury in Neonates after Congenital

Michelle Ramírez1, Sujata Chakravarti1, Melissa Busovsky-McNeal1

  • 1Pediatric Cardiac Intensive Care, NYU Hassenfeld Children's Hospital, New York, United States.

Journal of Pediatric Intensive Care
|June 23, 2022
PubMed

Insights

Urinary biomarkers tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) effectively identify acute kidney injury (AKI) in neonates post-congenital heart surgery. Elevated levels 24 hours after cardiopulmonary bypass predict AKI development.

Area of Science:

  • Nephrology
  • Pediatric Cardiology
  • Biomarker Discovery

Background:

  • Acute kidney injury (AKI) is a significant complication following congenital heart surgery (CHS).
  • Early and accurate identification of AKI is crucial for improving patient outcomes.
  • Existing diagnostic methods may have limitations in the neonatal population.

Purpose of the Study:

  • To evaluate the utility of urine biomarkers tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) for AKI detection in neonates undergoing CHS.
  • To assess the predictive value of the combined biomarker panel [TIMP-2*IGFBP-7] for AKI.
  • To correlate biomarker levels with AKI severity based on Acute Kidney Injury Network (AKIN) criteria.

Main Methods:

  • Prospective, single-center study involving neonates undergoing CHS with cardiopulmonary bypass (CPB).
  • Urine samples collected pre-surgery and at 6, 12, 24, and 96 hours post-CPB.
  • Analysis of urinary [TIMP-2*IGFBP-7] using NephroCheck and evaluation by AKIN criteria.
  • Statistical analysis including Wilcoxon rank sum tests and receiver operating characteristic (ROC) curves.

Main Results:

  • Out of 36 neonates, 19 (53%) developed AKI post-operatively (13 stage 1, 5 stage 2, 1 stage 3).
  • No patients required renal replacement therapy.
  • Significantly higher urinary [TIMP-2*IGFBP-7] levels were observed in patients with AKI compared to those without AKI at 24 hours post-CPB (1.1 vs. 0.27 [ng/mL]²/1,000; adj-p=0.0019).

Conclusions:

  • Urinary [TIMP-2*IGFBP-7] is a valuable and sensitive biomarker for predicting AKI in neonates after CHS.
  • The combined biomarker panel demonstrates strong predictive performance for AKI at 24 hours post-CPB.
  • This non-invasive method can aid in early AKI diagnosis and management in this vulnerable population.

Keywords:
acute kidney injurybiomarkerscardiopulmonary bypassheart defects, congenitalinsulin-like growth factor binding proteinstissue inhibitor of metalloproteinase-2

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