Relationship Between [TIMP-2]·[IGFBP-7] And Susceptibility And Prognosis Of Acute Kidney Injuryin Critically Ill Patients

Objective:To investigate the relationship between cell-cycle markers[Tissue inhibitor of metalloproteinases-2(TIMP-2)]·[Insulin-like growth factor binding protein-7(IGFBP-7)]and the susceptibility and prognosis of acute kidney injury(AKI)in critically ill patients.Methods:A multiple-center prospective observational method was adopted in this study.Patients that had been admitted to the intensive care unit(ICU)of Zhongda Hospital,southeast university,Northern Jiangsu People's Hospital and Wuxin Public Hospital from November 2017 to August 2018 were selected as study objects in accordance with inclusion conditions.The general materials include age,weight,gender,resource,APACHE II score,SOFA score and baseline creatinine(the lowest creatinine in six months between enrollment)were recorded.The urine[TIMP-2]·[IGFBP-7]levels at enrollment were tested by immunofluorescence.Serum creatinine levels at enrollment,12 hours after enrollment,urine volume of each hour,28-days mortality and days of ICU stay were tested and recorded.(1)AKI was diagnosed by KDIGO criteria.According to the diagnosis of AKI,patients were divided into the AKI group and the non-AKI group.(2)The relationship between[TIMP-2]·[IGFBP-7]and the occurrence,the severity of AKI,the use of CRRT and the 28-days mortality was evaluated.(3)The relationship between[TIMP-2]·[IGFBP-7]and the occurrence of AKI in sepsis patients and patients undergone cardiac surgery with cardiopulmonary bypass(CPB)was evaluated.(4)The area under curve(AUC)of receiver operating characteristic curve(ROC)was adopted to evaluate the efficiency of predicating the occurrence of AKI by[TIMP-2]·[IGFBP-7].Results:From December 2017 to March 2019,1380 patients were admitted to ICU,and286 patients were enrolled finally.Among these patients,38 patients developed AKI.14cases were diagnosed as mild AKI,19 cases were diagnoses as moderate AKI,and 5 cases were diagnoses as severe AKI.7 cases were conducted CRRT during ICU stay.The 28-days mortality was 16%.There was 240 cases in survival group,and 46 cases in non-survival group.1.Patients'baseline characteristics:There was no significant difference(p>0.05)in regards of gender,age,body weight,resources,baseline creatinine,APACHE II score,SOFA score and days of ICU stay in patients of the AKI group and non-AKI group.Compared with patients of non-AKI group,patients in AKI group were more often treated with vasoactive agents and mechanical ventilation(p<0.001).Compared with patients in non-AKI group,the in-hospital mortality(21%vs16%,p<0.001)and the probability of CRRT use(13%vs 0.8%,p<0.001)of patients in AKI group was higher.2.Relationship between[TIMP-2]·[IGFBP-7]and susceptibility of AKI in critically ill patients after 12 hours:[TIMP-2]·[IGFBP-7]of patients in AKI group was significantly higher than those of patients in non-AKI group[1.335(ng/ml)~2(0.715-2.340)vs.0.305(ng/ml)~2(0.150-0.628),p<0.001].The AUC of[TIMP-2]·[IGFBP-7]in predicting AKI after 12 hours was 0.845.The best cut-off level was 0.905(ng/ml)~2,the sensitivity was 0.71,the specificity was 0.94,the positive predictive value was 0.63,and the negative predictive value was 0.95.3.Relationship between[TIMP-2]·[IGFBP-7]and the severity of AKI in critically ill patients:38 cases(13%)were diagnosed as AKI after 12 hours according to KDIGO criteria.Among these patients,14 cases were diagnosed as mild AKI,19 cases were diagnoses as moderate AKI,and 5 cases were diagnoses as severe AKI.[TIMP-2]·[IGFBP-7]of patients in mild AKI group was 0.380(ng/ml)~2(0.190-1.060).[TIMP-2]·[IGFBP-7]of patients in moderate AKI group was 1.100(ng/ml)~2(0.550-1.730).[TIMP-2]·[IGFBP-7]of patients in severe AKI group was 2.220(ng/ml)~2(0.885-4.610).[TIMP-2]·[IGFBP-7]at enrollment increased with AKI deteriorated after 12 hours(p=0.029).The AUC of[TIMP-2]·[IGFBP-7]in predicting mild AKI,moderate AKI and severe AKI after 12 hours was 0.805,0.851 and 0.932,and the best cut-off level was 0.765(ng/ml)~2,0.905(ng/ml)~2 and 1.37(ng/ml)~2,respectively.4.Relationship between[TIMP-2]·[IGFBP-7]and the use of CRRT in critically ill patients:7 cases were conducted CRRT during ICU stay.Compared with patients in non-CRRT group,the[TIMP-2]·[IGFBP-7]of patients in CRRT group was significantly higher[1.000(ng/ml)~2(0.690-2.550)vs.0.310(ng/ml)~2(0.150-0.630),p<0.001].The AUC of[TIMP-2]·[IGFBP-7]in predicting the use of CRRT was 0.822.The best cut-off level was 1.270(ng/ml)~2,the sensitivity was 0.71,the specificity was 0.98,the positive predictive value was 0.12,and the negative predictive value was 0.98.5.Relationship between[TIMP-2]·[IGFBP-7]and prognosis in critically ill patients:The mortality in 28 days was 16%.There was 240 cases in survival group,and 46 cases in non-survival group.Compared with patients of survival group,[TIMP-2]·[IGFBP-7]of patients in non-survival group was significantly higher than those of patients in survival group[1.050(ng/ml)~2(0.270-1.375)vs.0.310(ng/ml)~2(0.140-0.540),p<0.001].The AUC of[TIMP-2]·[IGFBP-7]in predicting 28-days mortality was 0.759.The best cut-off level was 0.940(ng/ml)~2,the sensitivity was 0.53,the specificity was 0.97,the positive predictive value was 0.08,and the negative predictive value was 0.86.6.Relationship between[TIMP-2]·[IGFBP-7]and development of AKI in sepsis patients after 12 hours:Among 286 enrolled patients,81 patients had sepsis,and there was 9 patients developed AKI within 12 hours.[TIMP-2]·[IGFBP-7]of patients in AKI group was significantly higher than those of patients in non-AKI group[1.970(ng/ml)~2(1.170-2.875)vs.0.290(ng/ml)~2(0.143-0.600),p<0.001].The AUC of[TIMP-2]·[IGFBP-7]in predicting AKI after 12 hours was 0.966.The best cut-off level was 0.76(ng/ml)~2,the sensitivity was 1.00,the specificity was 0.81,the positive predictive value was 0.38,and the negative predictive value was 0.95.7.Relationship between[TIMP-2]·[IGFBP-7]and development of AKI in patients undergone cardiac surgery with CPB:Among 286 enrolled patients,26 patients underwent cardiac surgery with CPB,and there was 3 patients developed AKI after 12 hours.[TIMP-2]·[IGFBP-7]of patients in AKI group was significantly higher than those of patients in non-AKI group[1.430(ng/ml)~2 (1.010-3.430)vs.0.240(ng/ml)~2(0.160-0.480),p<0.001].The AUC of[TIMP-2]·[IGFBP-7]in predicting AKI after 12 hours was 0.859.The best cut-off level was 0.970(ng/ml)~2,the sensitivity was 0.88,the specificity was 0.93,the positive predictive value was 0.97,and the negative predictive value was 0.98.Conclusion:[TIMP-2]·[IGFBP-7]could be used for early prediction of AKI.It is of great clinical value for early detection of AKI severity,use of CRRT and prognosis of critically ill patients.