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.