Application Of Novel Urinary Biomarkers In Early Diagnosis And Progression Assessment Of Acute Kidney Injury In Patients With Decompensated Cirrhosis

Objective:By detecting urinary neutrophil gelatinase-associated lipocalin(NGAL),insulin-like growth factor binding protein-7(IGFBP-7),tissue inhibitor of metalloproteinases-2(TIMP-2)and kidney injury molecule-1(KIM-1),To determine the differences in the expression of urinary NGAL,IGFBP-7·TIMP-2 and KIM-1 in patients with decompensated cirrhosis and acute kidney injury(AKI)in cirrhosis.Furthermore,combined with the clinical data,the risk prediction model of AKI in cirrhotic patients and the prediction model of AKI progression based on novel urinary biomarkers were constructed to provide evidence for early clinical intervention.Methods:The clinical data of patients with decompensated cirrhosis without AKI at the time of admission at the Department of Infectious Diseases of the First Affiliated Hospital of Naval Medical University from November 2020 to February 2023 and urinary samples were collected the morning after admission.The concentrations of urinary NGAL,IGFBP-7,TIMP-2 and KIM-1 were detected by ELISA.According to the diagnostic criteria for AKI recommended by the International Ascites Club and the definition of AKI outcome,they were divided into AKI group and non-AKI group according to the occurrence of AKI during hospitalization.According to the disease outcome of AKI patients during hospitalization,they were divided into progressive and non-progressive groups.The urinary NGAL,IGFBP-7·TIMP-2,KIM-1 and main clinical data of patients in AKI group and non-AKI group,progressive group and non-progression group were used as variables for univariate analysis,the variables with statistical significance in univariate analysis were further analyzed by multivariate analysis,and the predictive model was constructed,the ROC curve was drawn and the area(AUC)value under the curve was calculated to evaluate the predictive effectiveness of the model.Results:Part 1:A total of 230 patients with decompensated cirrhosis admitted to the Department of Infectious Diseases of the First Affiliated Hospital of Naval Medical University from November 2020 to February 2023 were collected,including 79 patients in the AKI group and 151 in the non-AKI group.Univariate analysis showed that urinary NGAL,urinary IGFBP-7·TIMP-2,mean arterial pressure,albumin,serum sodium,prothrombin time,white blood cell count,platelet count,MELD score,total bilirubin,bacterial infection ratio,and upper gastrointestinal bleeding ratio were statistically significant(t=11.22,9.55,-2.23,-2.08,-2.01,3.95,2.49,-1.98,4.36,2.79,χ~2=25.73,10.07,all P<0.050),Statistically significant clinical data from univariate analysis were included in binary logistic regression analysis,and the results showed that bacterial infection(non-hematologic infection OR=4.404,95%CI 2.087～9.295,P<0.001;hematologic infection OR=7.381,95%CI 2.493～21.857,P<0.001),upper gastrointestinal bleeding(OR=3.335,95%CI 1.374～8.097,P=0.008),and MELD score(OR=1.093,95%CI 1.042～1.147,P<0.001)was the main risk factor for AKI,and the AUC value of the predicted model was 0.762.Statistically significant clinical data from univariate analysis,urinary NGAL,urinary IGFBP-7·TIMP-2 and urinary KIM-1 were included in binary logistic regression analysis,and the results showed that MELD score(OR=1.077,95%CI 1.007～1.151,P=0.030),urinary NGAL(OR=1.022,95%CI 1.015～1.030,P<0.001),urinary IGFBP-7·TIMP-2(OR=1.020,95%CI 1.012～1.027,P<0.001)were the main risk factors for AKI.The AUC value of the prediction model was 0.915,which was higher than that of the prediction model without novel biomarkers,MELD score,urinary NGAL and urinary IGFBP-7·TIMP-2(AUC=0.762,0.686,0.859,0.819).Part 2:According to the outcome of AKI patients during hospitalization,they were divided into a progressive group of 22 patients and a non-progressive group of 57 patients.Univariate analysis showed that urinary NGAL,urinary IGFBP-7·TIMP-2,total bilirubin,prothrombin time,serum sodium,MELD score,Upper gastrointestinal bleeding ratio and bacterial infection ratio were significantly different between the two groups(t=3.28,2.99,3.48,2.41,-2.31,4.03,χ~2=8.91,6.19,all P<0.050).Statistically significant clinical data from univariate analysis were included in binary logistic regression analysis,and the results showed that MELD score(OR=1.178,95%CI1.068～1.300,P=0.001)and upper gastrointestinal bleeding(OR=5.339,95%CI 1.529～18.648,P=0.009)was the main risk factor for AKI progression,and the AUC value of the predicted model was 0.802.Statistically significant clinical data from univariate analysis,urinary NGAL and urinary IGFBP-7·TIMP-2 were included in binary logistic regression analysis,and the results showed that MELD score(OR=1.195,95%CI 1.071～1.334,P=0.002),upper gastrointestinal bleeding(OR=6.185,95%CI 1.560～24.524,P=0.010)and urinary NGAL(OR=1.012,95%CI 1.003～1.021,P=0.007)were the main risk factors for AKI progression.The AUC value of the prediction model was 0.869,which was higher than that of the prediction model without new biomarkers,MELD score and urinary NGAL(AUC=0.802,0.760,0.680).Conclusion:AKI has a high incidence in patients with decompensated cirrhosis,and patients with severe bacterial infections,upper gastrointestinal bleeding,and high MELD scores should be warned during treatment.The prediction model constructed by MELD score,urinary NGAL and urinary IGFBP-7·TIMP-2 has better prediction value for patients with cirrhosis complicated with AKI.Patients with high MELD score and upper gastrointestinal bleeding are at greater risk for AKI progression,and the prediction model constructed in combination with urinary NGAL has strong predictive value for AKI progression.The inclusion of urinary NGAL and urinary IGFBP-7·TIMP-2 in the clinical evaluation of patients with decompensated cirrhosis has a certain guiding effect on clinical practice.It is necessary to strengthen the assessment and take targeted intervention measures early in clinical practice.