Urinary interleukin-18 and urinary neutrophil gelatinase-associated lipocalin predict acute kidney injury following pulmonary valve replacement prior to serum creatinine

Congenit Heart Dis. Sep-Oct 2012;7(5):441-7. doi: 10.1111/j.1747-0803.2012.00662.x. Epub 2012 Apr 27.


Background: It is becoming increasingly recognized that manifestations of congenital heart disease (CHD) extend beyond the cardiovascular system. The factors contributing to renal dysfunction in patients with CHD are multifactorial, with acute kidney injury (AKI) at time of cardiac surgery playing a major role. AKI is often diagnosed based on changes in serum creatinine and estimated glomerular filtration rate (eGFR). Such measurements are often late and imprecise. Recent data indicate that urinary biomarkers interleukin-18 (IL-18) and neutrophil gelatinase-associated lipocalin (NGAL) are earlier markers of AKI. We sought to determine the efficacy of urinary IL-18 and NGAL for detecting early AKI in patients undergoing surgical pulmonary valve replacement (PVR).

Methods: Twenty patients presenting for surgical PVR with a history of previous repair of a conotruncal anomaly were enrolled. Preoperative clinical data were measured and urine samples and serum creatinine were collected at 6, 12, 24, and 72 hours post bypass. Urine was evaluated for NGAL and IL-18. AKI was determined using the Risk, Injury, Failure, Loss and End Stage Renal Disease (RIFLE) classification system.

Results: Using the RIFLE classification system, seven patients (35%) were found to have AKI defined as a drop in the eGFR or an increase in serum creatinine. All seven patients with AKI had marked increase from preoperative baseline in urine IL-18 (sixfold) and NGAL (26-fold). Using NGAL and IL-18, AKI was detected at 6 hours postoperatively, resulting in AKI being identified 12-36 hours prior to detection by conventional methods. No preoperative predictors for AKI were identified.

Conclusion: Both NGAL and IL-18 are early predictive biomarkers of AKI, and both increase in tandem after surgical PVR. Importantly, both rise before an increase in creatinine or a decrease in eGFR is present. Monitoring both biomarkers may allow for earlier detection and subsequent interventions to prevent AKI at time of surgery for CHD.

Publication types

  • Evaluation Study

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / diagnosis*
  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / physiopathology
  • Acute Kidney Injury / urine
  • Acute-Phase Proteins / urine*
  • Adolescent
  • Adult
  • Biomarkers / blood
  • Biomarkers / urine
  • Child
  • Child, Preschool
  • Creatinine / blood*
  • Early Diagnosis
  • Female
  • Glomerular Filtration Rate
  • Heart Valve Prosthesis Implantation / adverse effects*
  • Humans
  • Interleukin-18 / urine*
  • Lipocalin-2
  • Lipocalins / urine*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Proto-Oncogene Proteins / urine*
  • Pulmonary Valve / surgery*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Young Adult


  • Acute-Phase Proteins
  • Biomarkers
  • Interleukin-18
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Creatinine