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Kidney Damage and Stress Biomarkers for Early Identification of Drug-Induced Kidney Injury: A Systematic Review

Author

Listed:
  • Ravi J. Desai

    (University of Pittsburgh, School of Pharmacy)

  • Christina L. Kazarov

    (University of Pittsburgh, School of Pharmacy)

  • Adrian Wong

    (Massachusetts College of Pharmacy and Health Sciences)

  • Sandra L. Kane-Gill

    (University of Pittsburgh, School of Pharmacy)

Abstract

Introduction Acute kidney injury (AKI) resulting from nephrotoxic medication use is prominent in hospitalized patients and is attributable to overall increases in mortality and costs of care. Serum creatinine (SCr), the current standard for identifying drug-induced AKI (DIAKI) is often delayed in its response to kidney insult by 26–36 h. Objective This systematic review seeks to evaluate the clinical utility of several novel kidney damage and stress biomarkers for the prediction/timely detection of DIAKI, in comparison with traditional methods. Methods A systematic review of the CINAHL, Cochrane Library, Embase, and PubMed databases was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, for articles analyzing the use of β2-microglobulin (B2M), interleukin (IL)-18, kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and tissue inhibitor of metalloproteinase-2 * insulin-like growth factor-binding protein 7 [TIMP-1]*[IGFBP-7], for identifying DIAKI. Primary outcomes included time to DIAKI diagnosis using traditional methods and the time to significant difference in biomarker concentrations between DIAKI and non-AKI study subjects. Secondary outcomes included biomarker concentrations at the time of significant difference between the AKI status groups. Results Fifteen unique articles were identified from the literature search. Twelve studies consisted of strictly hospitalized patient populations and three studies included hospitalized patients and patients discharged to home treatment. No studies reported values for urine volume output. Seventy-three percent of studies reported earlier times to significant difference of novel biomarker concentrations between the AKI and non-AKI groups than diagnosis of DIAKI by SCr alone. Significant variation was observed for individual urine biomarker concentrations at time of significant difference between the AKI status groups. Conclusions All analyzed biomarkers showed potential for use as early clinical markers of DIAKI, however further consensus on threshold urine concentrations for DIAKI is needed for meaningful implementation of these biomarkers in clinical practice.

Suggested Citation

  • Ravi J. Desai & Christina L. Kazarov & Adrian Wong & Sandra L. Kane-Gill, 2022. "Kidney Damage and Stress Biomarkers for Early Identification of Drug-Induced Kidney Injury: A Systematic Review," Drug Safety, Springer, vol. 45(8), pages 839-852, August.
    • Handle: RePEc:spr:drugsa:v:45:y:2022:i:8:d:10.1007_s40264-022-01202-2
    DOI: 10.1007/s40264-022-01202-2
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    References listed on IDEAS

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    1. Sandra L. Kane-Gill & Pamela L. Smithburger & Kianoush Kashani & John A. Kellum & Erin Frazee, 2017. "Clinical Relevance and Predictive Value of Damage Biomarkers of Drug-Induced Kidney Injury," Drug Safety, Springer, vol. 40(11), pages 1049-1074, November.
    2. David Moher & Alessandro Liberati & Jennifer Tetzlaff & Douglas G Altman & The PRISMA Group, 2009. "Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-6, July.
    3. Alessandro Liberati & Douglas G Altman & Jennifer Tetzlaff & Cynthia Mulrow & Peter C Gøtzsche & John P A Ioannidis & Mike Clarke & P J Devereaux & Jos Kleijnen & David Moher, 2009. "The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-28, July.
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