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.

Diagnostic prediction of urinary [TIMP-2] x [IGFBP7] for acute kidney injury: A meta-analysis exploring detection time and cutoff levels

“…The initial literature search found 103 potentially relevant articles, and among them, 24 articles that seemingly met our inclusion and exclusion criteria were downloaded for further perusal. Finally, a total of 10 articles written in English and published between 2014 and 2016 were considered in this meta-analysis [ 11 – 20 ].…”

“…Nine of ten studies ( n = 1597) were conducted in adult participants, and one study ( n = 51) in children [ 14 ]. Six studies ( n = 350) were conducted to evaluate the diagnostic value of urinary [TIMP-2] x [IGFBP7] for AKI after major surgeries (5 cardiac surgery [ 13 , 14 , 16 – 18 ] and 1 non-cardiac surgery [ 15 ]), and four studies ( n = 1298) were conducted among ICU patients [ 11 , 12 , 19 , 20 ]. The definition of AKI in eight studies accorded with the Kidney Disease: Improving Global Outcomes classification (KDIGO) criteria.…”

“…The definition of AKI in eight studies accorded with the Kidney Disease: Improving Global Outcomes classification (KDIGO) criteria. There was one study defining AKI according to the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) criteria [ 14 ] and the U-score [ 20 ], respectively.…”

Urinuntersuchung – Schritt für Schritt

“…Durch Spezialfärbungen können eosinophile Leukozyten in Einzelfällen angefärbt werden. leicht messbare Biomarker im Urin, die mit höheren Tubulusnekrose-Scores assoziiert sind [9].…”

Urinary TIMP2&middot;IGFBP7 for the prediction of platinum-induced acute renal injury

“…Many studies have shown that the product of the concentration of these proteins TIMP2·IGFBP7 in urine (Astute Medical, San Diego, CA, USA) is an early indicator of risk for AKI. [23][24][25][26][27][28] As the first available AKI biomarker test in the USA, urinary TIMP2·IGFBP7 was cleared in 2014 by the US FDA. 29 In this study, we tested the hypothesis that urinary TIMP2·IGFBP7 collected directly prior and after PBC administration can predict the development of AKI.…”