Diagnostic Value And Significance Of Tissue Inhibitor Of Urinary Matrix Metalloproteinase-2 And Urinary Insulin-like Growth Factor Binding Protein-7 In Septic AKI

Objective:The latest definition of sepsis is organ dysfunction that endangers the life of the host caused by infection.Despite advances in treatment,the mortality rate is still around40%.Sepsis-induced organ dysfunction,especially in the lungs and kidneys,is the most common.At present,the diagnostic criteria of acute renal injury in sepsis are still glomerular filtration rate,urine volume and serum creatinine,which often lead to delayed diagnosis because of its obvious lag.Therefore,searching for biomarkers for early diagnosis of acute kidney injury and timely detection and intervention will improve the prognosis of patients.Based on this,we observed and analyzed the value and significance of tissue inhibitor of matrix metalloproteinase-2(TIMP-2)and insulin-like growth factor binding protein-7(IGFBP-7)in the early diagnosis of sepsis AKI.Methods:Sepsis patients admitted to Shanghai City East Hospital emergency ICU from September 2017 to December 2018 were divided into sepsis AKI group and non-AKI group according to whether the patients had acute renal injury.The general clinical data of the patients were collected,and the urine samples of the patients with sepsis were collected for 10 ml at 0 hours,6 hours,12 hours,1days,3 days and 7 days after admission.The expression of TIMP-2 and IGFBP-7 in the urine samples of the patients was detected by ELISA.Pearson correlation analysis was used to analyze urinary TIMP-2,urinary IGFBP-7 and serum creatinine,urea nitrogen,sequential organ failure(SOFA)score,acute physiology and chronic health status score II(APACHEII)score.Subject working characteristic curve(ROC)was drawn and area under curve(AUC)was calculated to evaluate the diagnostic value of urinary TIMP-2 and urinary IGFBP-7for sepsis AKI.Result:1.Forty-five sepsis patients were enrolled,including 18 sepsis patients in non-AKI group and 27 sepsis patients in AKI group.The mortality rates of sepsis AKI and sepsis non-AKI groups were 59.3% and 27.8%,respectively.There were no significant differences in the indicators of ALT,aspartate aminotransferase,total bilirubin,lactate dehydrogenase,procalcitonin,white blood cell count,prothrombin time,D-dimer,fibrinogen,partially activated prothrombin time,brain natriuretic peptide,creatine kinase isoenzyme-B and interleukin-6 between the two groups at each time point.There were significant differences in platelet count,blood lactic acid level and SOFA score between sepsis non-AKI group and non-AKI group(p < 0.05).2.The concentration of urinary TIMP-2 in sepsis AKI group was significantly higher than that in sepsis non-AKI group and healthy group at 6 hours,12 hours,1 day,3 days and 7 days(p < 0.05),but there was no significant difference between sepsis AKI group and sepsis non-AKI group at 0 hours(p = 0.34).The concentration of urinary IGFBP-7 in sepsis AKI group at 0 hours,6 hours,12 hours,1 day,3 days and 7 days was higher than that in sepsis non-AKI group and healthy group,the difference was statistically significant(p < 0.05).3.Compared with the non-AKI group in sepsis,the area of urinary TIMP-2 under the curve of 0 hour,6 hours,12 hours,1 day,3 days,and 7 days was 0.627,0.642,0.734,0.947,respectively.0.714,0.543.At 1 day,the area under the curve reached a peak value of 0.947,and its sensitivity and specificity also reached peak values of 97.5% and81.2%,respectively,and the cutoff value was 151.23 ng/ml,which has a high diagnostic value.Compared with the non-AKI group in sepsis,the area of urinary IGFBP-7 under the curve of 0 hours,6 hours,12 hours,1 day,3 days,and 7 days was 0.754,0.958,1,0.86,respectively.0.701,0.707.At 12 hours,the area under the curve reached a peak of1,and its sensitivity and specificity also peaked at 12 hours,100% and 72.8%,respectively,and the cutoff value was 14.905 ng/ml,which had a high diagnostic value.4.Compared with non-AKI sepsis group,the area under the curve of combined detection of TIMP-2 and IGFBP-7 in sepsis AKI group was 0.873,0.988,1.00,0.953,0.730 and 0.814 in 0 hours,6 hours,12 hours,1 day,3 days and 7 days,respectively.Compared with urinary TIMP-2 and urinary IGFBP-7,the sensitivity and specificity were further improved.5.Urinary TIMP-2 and IGFBP-7 in sepsis AKI group were not correlated with urea nitrogen and creatinine.6.There was no correlation between urinary TIMP-2 and urinary IGFBP-7 and SOFA score and APACHEEII score in sepsis AKI group.Conclusion:1.Urine TIMP-2,urine IGFBP-7 and their combined ROC curves were significantly different between sepsis AKI group and sepsis non-AKI group.They had good sensitivity and specificity and could be used in the diagnosis of sepsis AKI.2.TIMP-2 and IGFBP-7 in urine have no correlation with SOFA score and APACHEII score,which are traditional indicators to evaluate the severity of disease.