A Clinical Study Of Urine Liver-type Fatty Acid Binding Protein Combined With Matrix Metalloproteinase-7 In Predicting The Progression Of Patients With IgA Nephropathy

Objective: To investigate the efficacy of urine liver-type fatty acid binding protein(u L-FABP)combined with urine matrix metalloproteinase-7(u MMP-7)in predicting the progression of patients with IgA nephropathy(IgAN)by establishing a prospective IgAN cohort.Methods: Patients with IgAN who were hospitalized or outpatient treatment at the Affiliated Hospital of Guilin Medical University from August2019 to June 2021 were enrolled.The morning urine samples were collected from the patients at baseline,and the levels of u L-FABP and u MMP-7 were detected by enzyme-linked immunosorbent assay(ELISA),and corrected by urine creatinine.Collecting the clinical data of the enrolled patients: age,gender,body mass index(BMI),systolic blood pressure,diastolic blood pressure,mean arterial pressure,hemoglobin,serum albumin,fasting blood glucose,triglyceride,total cholesterol,serum creatinine,estimated glomerular filtration rate(e GFR),blood urea nitrogen,uric acid,cystatin C,24-hours proteinuria,microscopic hematuria and Oxford classification(MEST-C)of renal pathology.Defining the progression of patients with IgAN: >40% decrease in e GFR;or end-stage kidney disease(ESKD);or death.According to the 75 th percentile level,it was divided into low u L-FABP level group(<662.83 pg/mg Cr)and high u L-FABP level group(≥662.83 pg/mg Cr).Spearman correlation was used to analyze the correlation of u L-FABP,u MMP-7 and clinical data separately.Using Logistic regression to analyze risk factors for IgAN progression.Using the receiver operating characteristic(ROC)curves to analyze the area under the curve(AUC)of u L-FABP,u MMP-7,u L-FABP+u MMP-7,u L-FABP+u MMP-7+clinical data for predicting the progression of IgAN.Cox proportional hazards model was used to analyze different level of u L-FABP for predicting the progression of IgAN.Kaplan-Meier method was used to analyze the renal survival rate of IgAN patients with different u L-FABP levels.Results: A total of 78 IgAN patients were enrolled with a median follow-up of 16 months,including 7 patients(4 males and 3 females)in the progressive group and 71 patients(36 males and 35 females)in the non-progressive group.There were statistically significant differences between the two groups in age,systolic blood pressure,diastolic blood pressure,mean arterial pressure,serum creatinine,e GFR,blood urea nitrogen,uric acid,cystatin C,24-hours proteinuria,and Oxford classification(tubular atrophy/interstitial fibrosis)(P<0.05).The level of u L-FABP [984.24(716.79)pg/mg Cr vs403.84(339.76)pg/mg Cr] in the IgAN progression group was significantly higher than that in the non-progression group(P<0.05).The correlation analysis results show that the level of u L-FABP in IgAN patients was positively correlated with age,systolic blood pressure,serum creatinine,blood urea nitrogen,uric acid,cystatin C,24-hours proteinuria,Oxford classification(tubular atrophy/interstitial fibrosis)(P<0.05),negatively correlated with e GFR(P<0.001).The level of u MMP-7 in IgAN patients was positively correlated with age,Oxford classification(segmental glomerulosclerosis),Oxford classification(tubular atrophy/interstitial fibrosis)(P<0.05),negatively correlated with e GFR,fasting blood glucose(P<0.05).After adjusting for the confounding factors such as age,gender,mean arterial pressure,e GFR,24-hours proteinuria,Oxford classification(tubular atrophy/interstitial fibrosis),multivariate logistic regression model showed that u L-FABP was an independent risk factor for predicting the progression of patients with IgAN(OR=1.002,P<0.05,95%CI:1.000-1.004).Multivariate Cox proportional hazards model adjusted for clinical data showed that compared with the low u L-FABP level group,HR for predicting the progression of IgAN in the high u L-FABP level group was 7.628(P<0.05,95%CI:1.030-56.492).ROC curve analysis showed that AUC of u L-FABP,u MMP-7,u L-FABP+u MMP-7,u L-FABP+u MMP-7+clinical data for predicting the progression of IgAN were0.831(P<0.05,95%CI:0.656-1.000),0.732(P<0.05,95%CI:0.544-0.921),0.891(P<0.05,95%CI:0.819-0-963),0.954(P<0.001,95%CI:0.893-1.000).The mean renal survival time of patients with IgAN in the high u L-FABP level group(22.58±2.00 months vs 27.43±0.41 months)was decreased(Log Rank P<0.05).Conclusions:(1)Urine L-FABP is correlated with age,systolic blood pressure,serum creatinine,e GFR,blood urea nitrogen,uric acid,cystatin C,24-hours proteinuria and Oxford classification(tubular atrophy/interstitial fibrosis).(2)Urine L-FABP is an independent risk factor for predicting the progression of patients with IgAN and is expected to serve as a new biomarker.(3)The hazard model constructed by urine L-FABP+urine MMP-7+clinical data can improve the efficacy in predicting the progression of patients with IgAN.