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. 2023 Aug;43(8):1029-1037.
doi: 10.1038/s41372-023-01684-7. Epub 2023 Apr 26.

Neonatal nephrotoxic medication exposure and early acute kidney injury: results from the AWAKEN study

Heidi J Steflik  1 , Jennifer R Charlton  2 , Meagan Briley  3 , David T Selewski  4 , Katja M Gist  5 , Mina H Hanna  6 , David Askenazi  7 , Russell Griffin  8 ; Neonatal Kidney Collaborative
Collaborators, Affiliations

Neonatal nephrotoxic medication exposure and early acute kidney injury: results from the AWAKEN study

Heidi J Steflik et al. J Perinatol. 2023 Aug.

Abstract

Background: We aimed to describe nephrotoxic medication exposure and investigate associations between exposure and acute kidney injury (AKI) in the neonatal intensive care unit during the first postnatal week.

Design/methods: Secondary analysis of the AWAKEN cohort. We evaluated nephrotoxic medication exposure during the first postnatal week and associations with AKI using time-varying Cox proportional hazard regressions models. Nephrotoxic medication exposure categories were defined as: no nephrotoxic medication, nephrotoxic medications excluding aminoglycosides, aminoglycoside alone, and aminoglycoside and another nephrotoxic medication.

Results: Of 2162 neonates, 1616 (74.7%) received ≥1 nephrotoxic medication. Aminoglycoside receipt was most common (72%). AKI developed in 211(9.8%) neonates and was associated with a nephrotoxic medication exposure (p < 0.01). Nephrotoxic medication exposures including a nephrotoxic medication excluding aminoglycoside (aHR 3.14, 95% CI 1.31-7.55) and aminoglycoside and another nephrotoxic medication (aHR 4.79, 95% CI 2.19-10.50) were independently associated with AKI and severe AKI (stage 2/3), respectively.

Conclusions: Nephrotoxic medication exposure in critically ill infants is common during the first postnatal week. Specific nephrotoxic medication exposure, principally aminoglycosides with another nephrotoxic medication, are independently associated with early AKI.

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Conflict of interest statement

Conflict of Interest: All authors report no real or perceived conflicts of interest that could affect the study design, collection, analysis, and interpretation of data, the writing of the report, or the decision to submit the manuscript for publication. For full disclosure, we provide the additional list of authors’ other funding sources that are not directly related to this study.

DJA is a consultant for Baxter, Nuwellis, Bioporto, and Seastar. His institution receives grant funding for education and research that is not related to this project from NIH, Baxter, Nuwellis, Medtronic, Bioporto, Portero, and Seastar. He has patents pending on inventions to improve the kidney care of neonates. He is the Founder and Chief Scientific Officer for Zorro-Flow Inc.

HJS received research grants with Baxter. No other disclosures were reported.

KG is a consultant for Bioporto and Potrero Medical.

JRC is on the Executive Board for the Neonatal Kidney Collaborative, a consultant for Medtronics, and an investor in Zorro-Flow.

Figures

Figure 1.
Figure 1.. Study Flow Diagram
AKI, acute kidney injury; NICU, neonatal intensive care unit; IVF, intravenous fluids; hrs, hours. *some patients were excluded for more than one reason.
Figure 2.
Figure 2.. Heat Map of Nephrotoxic Medication Exposure by Gestational Age and Postnatal Day
Heat maps demonstrating average number of nephrotoxic medications (y-axis on right) by gestational age groups (2-week bins, y-axis on left) and day of life (x-axis). Panel A. All neonates in cohort (n=2,162). Panel B. All neonates without early AKI (n=1,951). Panel C. All neonates with early, stage 1 AKI (n=121). Panel D. All neonates with early, severe AKI (n=90)
See this image and copyright information in PMC

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