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Clinical Relevance and Predictive Value of Damage Biomarkers of Drug-Induced Kidney Injury

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Abstract

Nephrotoxin exposure accounts for up to one-fourth of acute kidney injury episodes in hospitalized patients, and the associated consequences are as severe as acute kidney injury due to other etiologies. As the use of nephrotoxic agents represents one of the few modifiable risk factors for acute kidney injury, clinicians must be able to identify patients at high risk for drug-induced kidney injury rapidly. Recently, significant advancements have been made in the field of biomarker utilization for the prediction and detection of acute kidney injury. Such biomarkers may have a role both for detection of drug-induced kidney disease and implementation of preventative and therapeutic strategies designed to mitigate injury. In this article, basic principles of renal biomarker use in practice are summarized, and the existing evidence for six markers specifically used to detect drug-induced kidney injury are outlined, including liver-type fatty acid binding protein, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase-2 times insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]), kidney injury molecule-1 and N-acetyl-β-d-glucosaminidase. The results of the literature search for these six kidney damage biomarkers identified 29 unique articles with none detected for liver-type fatty acid binding protein and [TIMP-2]·[IGFBP7]. For three biomarkers, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and N-acetyl-β-d-glucosaminidase, the majority of the studies suggest utility in clinical practice. While many questions need to be answered to clearly articulate the use of biomarkers to predict drug-induced kidney disease, current data are promising.

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Fig. 1

(Adapted from the 10th Acute Dialysis Quality Initiative [ADQI] Consensus Conference; adqi.org) [13]

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Authors and Affiliations

  1. Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, 638 Salk Hall, 3501, Terrace St., Pittsburgh, PA, 15261, USA

    Sandra L. Kane-Gill & Pamela L. Smithburger

  2. The Center for Critical Care Nephology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Sandra L. Kane-Gill & John A. Kellum

  3. University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Sandra L. Kane-Gill, Pamela L. Smithburger & John A. Kellum

  4. Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Kianoush Kashani

  5. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Kianoush Kashani

  6. CRISMA (Clinical Research, Investigation and Systems Modeling of Acute Illness) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    John A. Kellum

  7. Department of Pharmacy and Medicine, Mayo Clinic, Rochester, MN, USA

    Erin Frazee

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Sandra L. Kane-Gill and Pamela L. Smithburger have no conflicts of interest that are directly relevant to the content of this article. Kianoush Kashani has received grant funding from Astute Medical. John A. Kellum has received grant support and consulting fees from Astute Medical and Bioporto. In addition, Dr. Kellum discloses intellectual property interests and licensing fees paid to the University of Pittsburgh by Astute Medical. Erin Frazee has received consulting fees from FAST Biomedical.

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Kane-Gill, S.L., Smithburger, P.L., Kashani, K. et al. Clinical Relevance and Predictive Value of Damage Biomarkers of Drug-Induced Kidney Injury. Drug Saf 40, 1049–1074 (2017). https://doi.org/10.1007/s40264-017-0565-7

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