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Use of urine neutrophil gelatinase-associated lipocalin for nephrotoxic medication acute kidney injury screening in neonates

Journal of Perinatology (2024)Cite this article

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Abstract

Background

Daily serum creatinine monitoring protocols for acute kidney injury (AKI) are invasive and may lead to surveillance resistance. We aimed to understand if use of urine neutrophil gelatinase-associated lipocalin (uNGAL) could increase high-risk nephrotoxic medication (NTMx) associated AKI screening adherence in neonates.

Methods

Statistical process control methods prior to and post implementation were trended. The primary outcome, screening adherence, was defined as either daily serum creatinine or uNGAL assessment through 2 days post high-risk NTMx exposure.

Results

1291 monitoring days from the pre-implementation era (4/2020-6/2021) were compared to1377 monitoring days from the post-era (6/2021-10/2022). AKI screening adherence increased (81 to 92%) following implementation of optional uNGAL screening. Urine NGAL accounted for 35% of screening obtained. Use of uNGAL resulted in a 40% reduction in blood sampling for serum creatinine.

Conclusions

Incorporation of uNGAL as a complementary screening tool to serum creatinine demonstrated sustained increased AKI surveillance in our Baby NINJA monitoring program.

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Fig. 1: Complementary screening algorithm.
Fig. 2: Screening adherence using either serum creatinine or uNGAL.
Fig. 3: Monitoring by serum creatinine.
Fig. 4: Flow diagram of uNGAL monitoring.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Rhone ET, Carmody JB, Swanson JR, Charlton JR. Nephrotoxic medication exposure in very low birth weight infants. J Matern Fetal Neonatal Med. 2014;27:1485–90.

    Article  CAS  PubMed  Google Scholar 

  2. Steflik HJ, Charlton JR, Briley M, Selewski DT, Gist KM, Hanna MH, et al. Neonatal nephrotoxic medication exposure and early acute kidney injury: results from the AWAKEN study. J Perinatol. 2023;43:1029–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Goldstein SL, Dahale D, Kirkendall ES, Mottes T, Kaplan H, Muething S, et al. A prospective multi-center quality improvement initiative (NINJA) indicates a reduction in nephrotoxic acute kidney injury in hospitalized children. Kidney Int. 2020;97:580–8.

    Article  CAS  PubMed  Google Scholar 

  4. Stoops C, Stone S, Evans E, Dill L, Henderson T, Griffin R, et al. Baby NINJA (nephrotoxic injury negated by just-in-time action): reduction of nephrotoxic medication-associated acute kidney injury in the neonatal intensive care unit. J Pediatr. 2019;215:223–8.e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jakacka N, Snarski E, Mekuria S. Prevention of iatrogenic anemia in critical and neonatal care. Adv Clin Exp Med. 2016;25:191–7.

    Article  PubMed  Google Scholar 

  6. Askenazi D. Are we ready for the clinical use of novel acute kidney injury biomarkers? Pediatr Nephrol. 2012;27:1423–5.

    Article  PubMed  Google Scholar 

  7. Gavigan HW, Slagle CL, Krallman KA, Poindexter BB, Hooper DK, Goldstein SL. Blood transfusion rates in Baby NINJA (nephrotoxic injury negated by just-in-time action)-a single-center experience. Pediatr Nephrol. 2021;36:1901–5.

    Article  PubMed  Google Scholar 

  8. Askenazi DJ, Montesanti A, Hundley H, Koralkar R, Pawar P, Shuaib F, et al. Urine biomarkers predict acute kidney injury and mortality in very low birth weight infants. J Pediatr. 2011;159:907–12.e1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Askenazi DJ, Koralkar R, Hundley HE, Montesanti A, Parwar P, Sonjara S, et al. Urine biomarkers predict acute kidney injury in newborns. J Pediatr. 2012;161:270–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Slagle CL, Goldstein SL, Gavigan HW, Rowe JA, Krallman KA, Kaplan HC, et al. Association between elevated urine neutrophil gelatinase-associated lipocalin and postoperative acute kidney injury in neonates. J Pediatr. 2021;238:193–201.e2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rumpel J, Spray BJ, Chock VY, Kirkley MJ, Slagle CL, Frymoyer A, et al. Urine biomarkers for the assessment of acute kidney injury in neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia. J Pediatr. 2022;241:133–40.e3.

    Article  CAS  PubMed  Google Scholar 

  12. Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, et al. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol. 2008;3:665–73.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lavery AP, Meinzen-Derr JK, Anderson E, Ma Q, Bennett MR, Devarajan P, et al. Urinary NGAL in premature infants. Pediatr Res. 2008;64:423–8.

    Article  CAS  PubMed  Google Scholar 

  14. Jansen D, Peters E, Heemskerk S, Koster-Kamphuis L, Bouw MP, Roelofs HM, et al. Tubular injury biomarkers to detect gentamicin-induced acute kidney injury in the neonatal intensive care unit. Am J Perinatol. 2016;33:180–7.

    Article  PubMed  Google Scholar 

  15. Goldstein SL, Krallman KA, Schmerge A, Dill L, Gerhardt B, Chodaparavu P, et al. Urinary neutrophil gelatinase-associated lipocalin rules out nephrotoxic acute kidney injury in children. Pediatr Nephrol. 2021;36:1915–21.

    Article  PubMed  Google Scholar 

  16. Askenazi DJ, Koralkar R, Patil N, Halloran B, Ambalavanan N, Griffin R. Acute kidney injury urine biomarkers in very low-birth-weight infants. Clin J Am Soc Nephrol. 2016;11:1527–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tabel Y, Elmas A, Ipek S, Karadag A, Elmas O, Ozyalin F. Urinary neutrophil gelatinase-associated lipocalin as an early biomarker for prediction of acute kidney injury in preterm infants. Am J Perinatol. 2014;31:167–74.

    PubMed  Google Scholar 

  18. Goldstein SL, Kirkendall E, Nguyen H, Schaffzin JK, Bucuvalas J, Bracke T, et al. Electronic health record identification of nephrotoxin exposure and associated acute kidney injury. Pediatrics. 2013;132:e756–67.

    Article  PubMed  Google Scholar 

  19. Jetton JG, Askenazi DJ. Acute kidney injury in the neonate. Clin Perinatol. 2014;41:487–502.

    Article  PubMed  Google Scholar 

  20. Selewski DT, Cornell TT, Heung M, Troost JP, Ehrmann BJ, Lombel RM, et al. Validation of the KDIGO acute kidney injury criteria in a pediatric critical care population. Intensive Care Med. 2014;40:1481–8.

    Article  PubMed  Google Scholar 

  21. Benneyan JC, Lloyd RC, Plsek PE. Statistical process control as a tool for research and healthcare improvement. Qual Saf Health Care. 2003;12:458–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. R Developement Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2020.

    Google Scholar 

  23. Ree IMC, Lopriore E. Updates in neonatal hematology: causes, risk factors, and management of anemia and thrombocytopenia. Hematol Oncol Clin North Am 2019;33:521–32.

    Article  PubMed  Google Scholar 

  24. Stoops C, Gavigan H, Krallman K, Anderson N, Griffin R, Slagle C, et al. The Utility of Urinary NGAL as an alternative for serum creatinine to detect acute kidney injury in infants exposed to nephrotoxic medications in the neonatal intensive care unit. Neonatology. 2023:1–10. https://doi.org/10.1159/000535322. Epub ahead of print.

  25. Askenazi DJ, Koralkar R, Levitan EB, Goldstein SL, Devarajan P, Khandrika S, et al. Baseline values of candidate urine acute kidney injury biomarkers vary by gestational age in premature infants. Pediatr Res. 2011;70:302–6.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Haase M, Devarajan P, Haase-Fielitz A, Bellomo R, Cruz DN, Wagener G, et al. The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol. 2011;57:1752–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Haase M, Kellum JA, Ronco C. Subclinical AKI–an emerging syndrome with important consequences. Nat Rev Nephrol. 2012;8:735–9.

    Article  CAS  PubMed  Google Scholar 

  28. Marcello M, Virzi GM, Mucino-Bermejo MJ, Milan Manani S, Giavarina D, Salvador L, et al. Subclinical AKI and clinical outcomes in elderly patients undergoing cardiac surgery: diagnostic utility of NGAL versus standard creatinine increase criteria. Cardiorenal Med. 2022;12:94–105.

    Article  CAS  PubMed  Google Scholar 

  29. Koyner JL. Subclinical acute kidney injury is acute kidney injury and should not be ignored. Am J Respir Crit Care Med. 2020;202:786–7.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Sellmer A, Bech BH, Bjerre JV, Schmidt MR, Hjortdal VE, Esberg G, et al. Urinary neutrophil gelatinase-associated lipocalin in the evaluation of patent ductus arteriosus and AKI in very preterm neonates: a cohort study. BMC Pediatr. 2017;17:7.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Previous presentations from various information included in this manuscript include an oral abstract presented at the American Society of Nephrology Kidney Week, on November 3rd, 2022, in Orlando, FL as well as a poster presentation at the AKI & CRRT conference, in San Diego, CA, and Pediatric Academic Societies Conference, Washington D.C, 2023.

Author information

Authors and Affiliations

  1. Division of Neonatology and Pulmonary Biology, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Cara L. Slagle

  2. Center for Acute Care Nephrology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Cara L. Slagle, Kelli A. Krallman & Stuart L. Goldstein

  3. Riley Hospital for Children at Indiana University Health and Indiana University School of Medicine, Indianapolis, IN, USA

    Cara L. Slagle

  4. Division of Pharmacy, Cincinnati Children’s Hospital, Cincinnati, OH, USA

    Trina Hemmelgarn

  5. Division of Nephrology, Levine Children’s Hospital, Charlotte, NC, USA

    Hailey W. Gavigan

  6. Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Kelli A. Krallman & Stuart L. Goldstein

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  1. Cara L. Slagle
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Contributions

CL Slagle was involved in conceptualization, methodology, data curation and analysis, and the writing of the original draft. TH was involved in conceptualization, methodology, data curation and analysis, and review of the original draft. HWG was involved in the conceptualization, methodology, data curation, and review of the original draft. KAK was involved in the conceptualization, methodology, data curation, and review of the original draft. SLG was involved in the conceptualization, methodology, and review of the original draft.

Corresponding author

Correspondence to Cara L. Slagle.

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Competing interests

Cara Slagle, MD is a consultant for AM Pharma and Medtronic and has received honorariums from Medtronic, the University of Alabama, and the AKI Critical Care Foundation, all unrelated to the work above. Stuart Goldstein, MD and Cincinnati Children’s Hospital receive royalties from Vigilanz Corporation (Minneapolis, MN) for the NINJA application licensed to Vigilanz from Cincinnati Children’s Hospital Medical Center. Dr. Goldstein consults and receives research funding from BioPorto Diagnostics, Inc, which markets The ProNephroAKI NGAL Test™.

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Author has moved institutions since time of initial submission: Cara Slagle.

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Slagle, C.L., Hemmelgarn, T., Gavigan, H.W. et al. Use of urine neutrophil gelatinase-associated lipocalin for nephrotoxic medication acute kidney injury screening in neonates. J Perinatol (2024). https://doi.org/10.1038/s41372-024-01922-6

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  • DOI: https://doi.org/10.1038/s41372-024-01922-6

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