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

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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.

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Authors and Affiliations

  1. University of Pittsburgh, School of Pharmacy, Pittsburgh, PA, USA

    Ravi J. Desai & Christina L. Kazarov

  2. Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA

    Adrian Wong

  3. University of Pittsburgh, School of Pharmacy, 6462 Salk Hall, 3507 Terrace St, Pittsburgh, PA, 15261, USA

    Sandra L. Kane-Gill

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  1. Ravi J. Desai
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Correspondence to Sandra L. Kane-Gill.

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The authors did not receive any funding for the research or authorship of this study.

Conflicts of interest

Ravi Desai, Christina L. Kazarov, and Adrian Wong have no disclosures to declare. Sandra L. Kane-Gill declares the following: Organizational Leadership: President-Elect of the Society of Critical Care Medicine (SCCM); National Institute of Diabetes and Digestive and Kidney Diseases and National Center for Complementary and Integrative Health grant funding.

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Authors’ contributions

Ravi Desai contributed to the study conceptualization, search execution, article screening, manuscript writing, and project oversight. Christina Kazarov contributed to the study conceptualization, article screening, and manuscript writing. Sandra Kane-Gill contributed to the study conceptualization, manuscript writing, and project oversight. Adrian Wong contributed to the study conceptualization and manuscript writing. All authors read and approved the final version of this manuscript.

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Desai, R.J., Kazarov, C.L., Wong, A. et al. Kidney Damage and Stress Biomarkers for Early Identification of Drug-Induced Kidney Injury: A Systematic Review. Drug Saf 45, 839–852 (2022). https://doi.org/10.1007/s40264-022-01202-2

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