Integration of the Renal Angina Index and Urine Neutrophil Gelatinase-Associated Lipocalin Improves Severe Acute Kidney Injury Prediction in Critically Ill Children and Young Adults

Stuart L. Goldstein*, Kelli A. Krallman, Cassie Kirby, Jean Philippe Roy, Michaela Collins, Kaylee Fox, Alexandra Schmerge, Sarah Wilder, Bradley Gerhardt, Ranjit Chima, Rajit K. Basu, Lakhmir Chawla, Lin Fei

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Introduction: Acute kidney injury (AKI) occurs in one-fourth of children and young adults admitted to pediatric intensive care unit (PICU). Severe AKI (sAKI; Kidney Disease: Improving Global Outcomes stage 2 or 3) is associated with morbidity and mortality. An AKI risk stratification system, the Renal Angina Index (RAI) calculated at 12 hours of admission, exhibits excellent performance to rule out sAKI at 72 hours of admission. We found that integration of urine neutrophil gelatinase-associated lipocalin (NGAL) with RAI improves prediction of sAKI. We now report the first-year results after implementation of our prospective automated RAI-NGAL clinical decision support (CDS) program. Methods: Patients 3 months to 25 years of age were eligible. Admission order sets have a conditional order for urine NGAL released when a 12-hour RAI ≥8. The primary outcome was sAKI any time at days 2 to 4 of admission. We assessed performance of the RAI and RAI+/NGAL to predict the primary outcome. Results: A total of 1427 unique patients accounted for 1575 admissions. In 147 admissions, RAI was ≥8. RAI <8 had negative predictive value (NPV) of 0.98 (95% CI 0.97–0.99); RAI ≥ 8 had positive predictive value (PPV) of 0.37 (95% CI 0.30–0.46) to predict days 2 to 4 sAKI (area under the receiver operating characteristic curve [AUC-ROC] 0.88 [95% CI 0.84–0.92]). Of 147 RAI+ patients, 89 had NGAL available. RAI/NGAL combination improved PPV (0.64, 95% CI 0.50–0.79) without decrement in NPV (0.98, 95% CI 0.97–0.98). Conclusion: AKI biomarker assessment directed by risk stratification improves prediction of sAKI in critically ill children and young adults. This CDS process has potential to enrich the population for interventional study, although improvement to adherence to CDS is needed.

Original languageEnglish (US)
Pages (from-to)1842-1849
Number of pages8
JournalKidney International Reports
Volume7
Issue number8
DOIs
StatePublished - Aug 2022

Funding

The methods for this prospective Trial in AKI using NGAL and Fluid Overload to optimize CRRT Use (TAKING FOCUS 2) have been reported elsewhere. 13 Briefly, all patients 3 months to 25 years of age admitted to the Cincinnati Children’s Hospital Medical Center PICU were eligible for enrolment. We used an upper age limit of 25 years as children with chronic illness are often cared for until age 25 years when they mature to young adult age. Exclusions included subjects admitted to PICU for <48 hours, history of baseline chronic kidney disease stage 4 or 5, an active do not resuscitate order or the clinical team is not committed to escalating medical care, or AKI requiring KRT before the PICU admission. The TAKING FOCUS 2 protocol was approved by the Cincinnati Children’s Hospital Medical Center Institutional Review Board, and as this was an observational study without an intervention, the study received a waiver of the need for informed consent. TAKING FOCUS 2 was registered on ClinicalTrials.gov (NCT03541785) before patient enrolment and is supported by the Cincinnati Children’s Hospital Innovation Fund and by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (P50 DK 096418-06). We used a REDCap database, a project supported by the National Center for Advancing Translational Sciences of the National Institutes of Health, under award number UL1TR000077. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Keywords

  • acute kidney injury
  • neutrophil gelatinase-associated lipocalin
  • renal angina index
  • severe AKI

ASJC Scopus subject areas

  • Nephrology

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