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Incidence of Antimicrobial-Associated Acute Kidney Injury in Children: A Structured Review

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Abstract

Acute kidney injury (AKI) is a commonly reported adverse effect of administration of antimicrobials. While AKI can be associated with poorer outcomes, there is little information available to understand rates of AKI in children exposed to various antimicrobials. We performed a structured review using the PubMed and Embase databases. Articles were included if they provided an AKI definition in patients who were < 19 years of age receiving an antimicrobial and reported the frequency of AKI. Author-defined AKI rates were calculated for each study and mean pooled estimates for each antimicrobial were derived from among all study participants. Pooled estimates were also derived for those studies that reported AKI according to pRIFLE (pediatric risk, injury, failure, loss, end stage criteria), AKIN (acute kidney injury network), or KDIGO (kidney disease improving global outcomes) creatinine criteria. A total of 122 studies evaluating 28 antimicrobials met the inclusion criteria. Vancomycin was the most commonly studied drug: 11,514 courses across 44 included studies. Among the 27,285 antimicrobial exposures, the overall AKI rate was 13.2% (range 0–42.1% by drug), but the rate of AKI varied widely across studies (range 0–68.8%). Cidofovir (42.1%) and conventional amphotericin B (37.0%) had the highest pooled rates of author-defined AKI. Eighty-one studies used pRIFLE, AKIN, or KDIGO AKI criteria and the pooled rates of AKI were similar to author-defined AKI rates. In conclusion, antimicrobial-associated AKI is reported to occur frequently in children, but the rates of AKI varies widely across studies and drugs. Most published studies examined hospitalized patients and heterogeneity in study populations and in author definitions of AKI are barriers to a comparison of nephrotoxicity risk among antimicrobials in children.

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Authors and Affiliations

  1. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Torsten Joerger & Kevin J. Downes

  2. Division of Infectious Diseases, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA

    Torsten Joerger, Ibram Mikhail & Kevin J. Downes

  3. Center for Healthcare Quality and Analytics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Molly Hayes

  4. Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA

    Connor Stinson

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Ibram Mikhail is supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM008562. Kevin J. Downes is supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number K23HD091365.

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Torsten Joerger, Molly Hayes, Connor Stinson, Ibram Mikhail, and Kevin J. Downes have no conflicts of interest that are directly relevant to the content of this article.

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Authors’ contributions

KJD conceptualized and designed the study. TJ, MH, and KJD screened articles for inclusion and exclusion criteria. TJ, MH, KJD, CS, and IM extracted rates of nephrotoxicity from selected articles and IM compiled summarizing information into Table 1 of the ESM. TJ and KJD analyzed the data and wrote the manuscript. All authors reviewed, provided critical feedback, and approved the final version.

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Joerger, T., Hayes, M., Stinson, C. et al. Incidence of Antimicrobial-Associated Acute Kidney Injury in Children: A Structured Review. Pediatr Drugs 26, 59–70 (2024). https://doi.org/10.1007/s40272-023-00607-5

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