Urinary [TIMP-2]·[IGFBP7] - Novel Biomarkers to Predict Acute Kidney Injury

Abstract

Background: Urine microscopy is an established technique to assess kidney disease, and can add valuable information about the mechanism of damage. However, it requires the time and expertise of an experienced nephrologist and, therefore, is typically used for a limited number of patients in practice. A rapid biomarker test that identifies patients from the emergency department (ED) who are likely to have positive urine microscopy findings would enable more efficient use of this technique.

Methods: Four hundred patients were enrolled in the ED; thereof 362 patients had available both tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2]·[IGFBP7] and urine score (U-Score) data at enrollment. U-Score was assessed through urine microscopy as described previously.

Results: Fifteen (4%) of 362 patients had a U-Score >0. When patients were stratified into 3 groups using the validated [TIMP-2]·[IGFBP7] cutoffs of 0.3 and 2.0, the proportion of patients with a positive U-Score increased across the 3 strata from 1 to 6 to 24% (p < 0.001). At the 0.3 cutoff, [TIMP-2]·[IGFBP7] had a sensitivity of 87%, specificity of 62% and negative predictive value (NPV) of 99% for prediction of a positive U-Score. At the 2.0 cutoff, specificity increased to 95% and positive predictive value (PPV) increased to 24%.

Conclusions: In ED patients, urinary [TIMP-2]·[IGFBP7] had a high NPV (99%) for ruling out a positive U-Score using the 0.3 cutoff and had a PPV of 24% (6-fold greater than the pre-test probability) using the 2.0 cutoff. As such, urinary [TIMP-2]·[IGFBP7] may enable more effective use of urine microscopy in these patients and thereby save time and personnel resources.

Summary: Urine microscopy is an established technique to assess acute kidney injury and can add valuable information about the mechanism of damage; however it requires the time and expertise of an experienced nephrologist and, therefore, is typically used for a limited number of patients in clinical practice. We have shown in ED patients, urinary [TIMP-2]·[IGFBP7] had a high NPV (99%) for ruling out a positive U-Score using the 0.3 cutoff and had a PPV of 24% (6-fold greater than the pre-test probability) using the 2.0 cutoff. As such, urinary [TIMP-2]·[IGFBP7] may enable more effective use of urine microscopy in these patients and thereby save time and personnel resources.