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Acute kidney injury biomarkers offer the opportunity to reduce exposure to nephrotoxic drugs

Introduction

Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are specific urinary biomarkers which can predict acute kidney injury (AKI) in critically ill patients within 12 hours [1]. A [TIMP-2]·[IGFBP7] result >0.3 (ng/ml)2/1,000 is associated with seven times the risk of AKI compared with a test result ≤0.3 [2]. The aim of our study was to explore the use of potentially nephrotoxic medications within the window between a positive biomarker test and the diagnosis of AKI stage 2 or 3.

Methods

We identified all patients enrolled into the Sapphire study [1] who received at least one potentially nephrotoxic drug on the day of AKI (defined by stage 2 or 3 as per KDIGO classification). We subsequently determined the proportion of patients who had a [TIMP-2]·[IGFBP7] result >0.3 (ng/ml)2/1,000 before meeting the criteria for AKI.

Results

Of 184 patients who developed AKI, 58% received one or more potentially nephrotoxic drug on the day of AKI. Eighty-nine percent of these patients had a positive biomarker test ≥12 hours earlier. In 41% of patients receiving one or more nephrotoxic drug on the day of AKI, at least one nephrotoxic medication was stopped within 1 day of AKI, and in 24% of patients all nephrotoxic drugs were stopped within 1 day of AKI, which implies that these medications were not absolutely necessary.

Conclusion

Nephrotoxic medications are commonly used in patients who develop moderate or severe AKI. The [TIMP-2]·[IGFBP7] test could have identified many of these patients earlier and would have offered an opportunity to reduce exposure to non-essential nephrotoxic drugs.

References

  1. 1.

    Kashani K, et al: Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013, 17: R25-10.1186/cc12503.

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  2. 2.

    Bihorac A, et al: Validation of cell-cycle arrest biomarkers for acute kidney injury: using clinical adjudication. Am J Resp Crit Care Med. 2014, 932-9. 189

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Ostermann, M., Forni, L., Kashani, K. et al. Acute kidney injury biomarkers offer the opportunity to reduce exposure to nephrotoxic drugs. Crit Care 19, P295 (2015). https://doi.org/10.1186/cc14375

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Keywords

  • Growth Factor
  • Emergency Medicine
  • Sapphire
  • Factor Binding
  • Acute Kidney Injury
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