Predictive values of urinary metalloproteinases-2 and insulin-like growth factor-binding protein 7 for contrast medium-induced acute kidney injury

ObjectiveTo explore the expressions of tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) in renal tissue and urine after an injury of contrast medium (CM) and the prediction values of urinary TIMP-2 and IGFBP7 for contrast-induced acute kidne...

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Main Authors: Zou Xiao-biao, Bao Wei-wei, Huang Xiao-ying, Lu Chen, Chen Juan, Wang Zhi-qing, Huang Ming-fang
Format: Article
Language:zho
Published: Editorial Department of Journal of Clinical Nephrology 2022-03-01
Series:Linchuang shenzangbing zazhi
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Online Access:http://www.lcszb.com/thesisDetails#10.3969/j.issn.1671-2390.2022.03.008
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Summary:ObjectiveTo explore the expressions of tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) in renal tissue and urine after an injury of contrast medium (CM) and the prediction values of urinary TIMP-2 and IGFBP7 for contrast-induced acute kidney injury (CI-AKI) in patients with primary percutaneous coronary intervention (PPCI).MethodsTwenty male Sprague-Dawley rats were divided randomly into two groups of CI-AKI (<italic>n</italic>=9) and control (<italic>n</italic>=11). Serum creatinine (Scr) level was measured before an injection of CM or normal saline (NS) and at 24h post-intervention. Kidney samples,containing both cortex and medulla,were harvested for hematoxylin-eosin (HE) staining and immunohistochemistry. Urinary samples for TIMP-2 and IGFBP7 were collected at 4/12/24 h post-injection. From January 2019 to December 2020,116 patients undergoing PPCI were recruited. Baseline profiles and laboratory findings were recorded. Receiver operating curves (ROC) of urinary TIMP-2/IGFBP7 concentrations at 6 h post-CI-AKI were evaluated for the possibility of serving as potential biomarkers in early prediction of CI-AKI.ResultsAs compared with control group,the average elevation of Scr was over baseline in CI-AKI group (<italic>P</italic>&lt;0.05). CM intervention induced marked histopathological changes in kidney tissue,including vacuole-like denaturation,nucleus pyknosis and apoptotic body formation. The mean Paller score was significantly higher in CI-AKI group. A robust formation of autophagosome was observed with transmission electron microscope in CI-AKI group. Rising significantly and peaking at 4 h after CM injection,urinary levels of TIMP-2 were higher than those in controls at the same observation timepoints (<italic>P</italic>&lt;0.05). Urinary IGFBP7 levels were markedly up-regulated at 4 h after CM injection and peaked within 12 h. And the values were higher than those in controls at the same observation timepoints (<italic>P</italic>&lt;0.05). The expression of TIMP-2/IGFBP7 was significantly elevated in renal tubular epithelial cells after CM injury. CI-AKI occurred in 16/109 patients with an incidence of 20.8%. As comparing with control group,urinary level of TIMP-2/IGFBP7 of CI-AKI group was significantly elevated at 6 h post-operation(<italic>P</italic>&lt;0.05). For an onset of CI-AKI after PPCI,PLR had an area under the curve (AUC) value of 0.841 on ROC. For a cutoff value of 0.33,urinary TIMP-2/IGFBP7 had a sensitivity of 75.0% and a specificity of 89.3% for predicting CI-AKI.ConclusionThe expressions of TIMP-2 and IGFBP7 are markedly up-regulated in proximal tubular epithelial cells and urine after CM injury. Urinary level of TIMP-2/IGFBP7 is an early predictor of CI-AKI in PPCI patients.
ISSN:1671-2390