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

Objective To 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）.Methods Twenty male Sprague-Dawley rats were divided randomly into two groups of CI-AKI （n=9） and control （n=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.Results As compared with control group，the average elevation of Scr was over baseline in CI-AKI group （P<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 （P<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 （P<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（P<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.Conclusion The 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.