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Am J Perinatol
DOI: 10.1055/a-2816-0051
Review Article

A Pathophysiological Approach for Early Detection and Prevention of AKI in the NICU

Authors

  • Vignesh Gunasekaran  ‡   ‡

    1   Department of Pediatrics/Neonatology, West Virginia University School of Medicine, Martinsburg, West Virginia, United States

  • Soowan Woo  ‡   ‡

    2   Department of Pediatrics, Gyeongsang National University College of Medicine, Jinju, Republic of Korea

  • Parvathy Krishnan

    3   Division of Newborn Medicine, Tufts University School of Medicine, Boston, Massachusetts, United States

  • Andrew M. South

    4   Department of Pediatrics/Section of Nephrology, Wake Forest University School of Medicine, Winston Salem, North Carolina, United States
    5   Division of Public Health Sciences/Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston Salem, North Carolina, United States

  • Jeffrey Shenberger

    6   Department of Pediatrics/Neonatology, Connecticut Children's, Hartford, Connecticut, United States

  • David Askenazi

    7   Department of Pediatrics/Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, United States

  • Parvesh M. Garg

    8   Department of Pediatrics/Neonatology, Atrium Health Wake Forest Baptist, Wake Forest School of Medicine, Winston Salem, North Carolina, United States

Funding Information P.M.G. is partially supported by the NIGMS of the NIH under award number, U54GM115428. A.M.S. is supported by NIH (grant nos.: NHLBI R01HL146818, NIH NHLBI K23HL148394, and NIH NHLBI R01HL164434). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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Abstract

This study aimed to summarize contemporary evidence on the definition, epidemiology, risk factors, and prevention of acute kidney injury (AKI) in critically ill and preterm infants in the neonatal intensive care unit (NICU), and to highlight prevention-focused strategies to improve outcomes. Narrative review of current literature evaluating AKI burden, diagnostic criteria, modifiable and nonmodifiable risk factors, and preventive interventions in neonatal intensive care settings. AKI is common in critically ill and preterm infants and is associated with increased mortality, prolonged hospitalization, neurodevelopmental impairment, and progression to chronic kidney disease. Modified Kidney Disease: Improving Global Outcomes criteria have improved diagnostic consistency and revealed particularly high AKI prevalence in extremely low birth weight infants. Key modifiable risk factors include hemodynamic instability, patent ductus arteriosus, nephrotoxic drug exposure, fluid overload, and sepsis, while preventive strategies span optimized antenatal management, therapeutic hypothermia for hypoxic ischemic encephalopathy, careful postnatal hemodynamic and fluid management, nephrotoxic drug stewardship, early infection control, individualized ductus arteriosus therapy, and potential use of caffeine, alongside emerging urinary biomarkers for earlier detection. Given limited therapeutic options once AKI occurs, prevention through structured surveillance, timely identification of high-risk states, and rigorous implementation of kidney protective practices is essential. Integrating quality improvement, protocolized care pathways, and educational outreach within NICUs offers the greatest promise for improving short and long-term outcomes in infants with AKI.

Key Points

  • Structured post-AKI monitoring and quality improvement protocols reduce AKI incidence.

  • Nephrotoxic medication protocols reduce AKI through proactive monitoring and dose optimization.

  • Neonatal AKI is common and serious; prevention via fluids, hemodynamics, and med stewardship is key.

Keywords

acute kidney injury - preterm infant - neonate - serum creatinine - nephrotoxicity - fluid balance

Impact Statement

1. Neonatal AKI is common, caused by multiple etiologies, and affects critically ill neonates with significant morbidity. Since treatment options are limited, preventing kidney injury through hemodynamic optimization, fluid management, and medication stewardship is essential.


2. Implementation of structured nephrotoxic medication management protocols reduces medication-associated AKI, highlighting the impact of proactive drug monitoring and dose optimization.


3. Structured post-AKI monitoring and quality improvement protocols reduce AKI incidence and prevent long-term kidney disease in neonates.


Informed Consent

Patient consent was not required as per the IRB.


‡ These authors contributed equally to this article.




Publication History

Received: 27 January 2026

Accepted: 17 February 2026

Accepted Manuscript online:
19 February 2026

Article published online:
27 February 2026

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