Study On Association Between Urinary Liver-type Fatty Acid Binding Protein And Inflammatory Response In Chronic Kidney Disease

Objective: Some studies have shown that liver-type fatty acid binding protein is a sensitive biomarker that can early predict tubulerinterstitial damage.In recent years,some researchers found that L-FABP was related to the progress of chronic kidney disease.This study aims to understand the molecular mechanism of L-FABP in the progress of chronic kidney disease,risk factors of the progress of kidney function,specificity and sensitivity of L-FABP predicting the progress of kidney function by testing urinary L-FABP,serum and urinary TNF-α,serum MCP-1,and collecting clinical biochemical indicators.Methods: 141 patients with chronic kidney disease diagnosed on clinic in our hospital for the first time were enrolled from December 2014 to December 2015.The simplified MDRD formula was applied to evaluate glomerular filtration rate.They were divided into five groups according to CKD stages.38 cases of normal healthy adults were enrolled as the control group during the same time in our hospital examination center.The patients’ clinical data of general condition and serum or urinary indexes were recorded,including gender,age,smoking history,drinking history,history of high blood pressure,height,weight,systolic blood pressure(SBP),diastolic blood pressure(DBP),renal biopsy report,hemoglobin(HGB),serum albumin(ALB),alanine aminotransferase(ALT),aspertate aminotransferase(AST),blood urea nitrogen(BUN),serum creatinine(SCr),blood uric acid(UA),β2 microglobulin(β2-MG),total cholesterol(CHOL),triglyceride(TG),high-density lipoprotein(HDL),low density lipoprotein(LDL),fasting blood glucose(FBG),C-reactive protein(CRP),the initial 24 hours urinary protein quantitative(uPRO),urine osmotic pressure(Uosm),urinary creatinine(uCr).The level of urinary L-FABP,serum and urinary TNF-α,serum MCP-1 were measured by enzyme-linked immunosorbent assay.The results of urinary L-FABP and urinary TNF-α had to be divided by urinary creatinine.All data were processed and analysed by SPSS13.0 software.Results: 1 The general data: There were 141 cases of patients with CKD.86 patients had renal pathologic results,including 46 cases of membranous nephropathy,11 minimal change disease,9 IgA nephropathy,3 amyloidosis,2 lupus nephritis and 15 other cases.CKD patients(male 102 cases,female 39 cases),with mean age(47.14±15.39).There were 38 cases of the control group(male 20 cases,female 18 cases),with average age(41.94±13.52).SBP,DBP,BUN,SCr,UA,β2-MG,CHOL,TG,LDL,HDL of CKD group were higher than the control group and ALB,eGFR were lower than the control group.The difference was statistically significant.There were no statistical significance between the two groups in gender,age,BMI,ALT,AST,FBG.2 The simplified MDRD formula was applied to evaluate glomerular filtration rate.They were divided into five groups according to CKD stages.CKD 1 group(eGFR≥90 ml/min/1.73m~2),44 cases,28 male and 16 female,mean age(41.55±14.22);CKD 2 group(60≤eGFR < 90 ml/min/1.73m~2),26 cases,20 male and 6 female,mean age(48.12±15.60);CKD 3 group(30≤eGFR<60 ml/min/1.73m~2)25 cases,19 male and 6 female,mean age(51.40±16.22);CKD 4 group(15≤eGFR<30 ml/min/1.73m~2)21 caese,16 male and 5 female,mean age(50.25±17.08);CKD 5 group(eGFR<15 ml/min/1.73m~2)25 cases,19 male and 6 female,mean age(49.24±13.03).Among five groups,there were no statistical significance in gender,age,DBP,BMI,ALT,AST,FBG,uPRO(P﹥0.05),whereas eGFR,SBP,HGB,CRP,ALB,BUN,SCr,UA,β2-MG,CHOL,TG,LDL,HDL and Uosm were significantly different(P﹤0.05).Chi-square test revealed the history of high blood pressure was different(χ2=20.297,P =0.000).3 The change of urinary L-FABP 3.1 Compared with control group,urinary L-FABP in the CKD group was obviously higher,the difference was statistically significant [(46.78 + 19.83)ug/g · Cr vs(8.23 + 4.72)u g/g · Cr,P < 0.05].3.2 Comparison among the five groups: urinary L-FABP increased with CKD stages.The difference was statistically significant[(25.19±10.92)μg/g·Cr vs(31.71±15.80)μg/g·Cr vs(41.85±17.44)μg/g·Cr vs(51.78±15.25)μg/g·Cr vs(76.16±24.91)μg/g·Cr,P<0.05].4 The change of urinary TNF-α,serum TNF-α,serum MCP-14.1 Compared with control group,urinary TNF-α,serum TNF-α,serum MCP-1 in the CKD group were obviously higher,the differences were statistically significant,[respectively(23.92±3.29)ng/mg·Cr vs(18.08±5.69)ng/mg·Cr,(17.16±7.09)pg/ml vs(13.07±6.05)pg/ml,(210.55±52.46)pg/ml vs(186.18±70.97)pg/ml,P<0.05].4.2 Comparison among the five groups: urinary TNF-α,serum TNF-α,serum MCP-1 increased with CKD stages [respectively(13.82±7.94)ng/mg·Cr vs(14.85±7.66)ng/mg·Cr vs(26.64±11.75)ng/mg·Cr vs(31.32±12.51)ng/mg·Cr vs(41.61±16.36)ng/mg·Cr,(14.90±6.69)pg/ml vs(15.26±5.02)pg/ml vs(18.11±5.91)pg/ml vs(20.70±1.96)pg/ml vs(22.37±3.02)pg/ml,(167.98± 56.53)pg/ml vs(175.17±84.99)pg/ml vs(194.84±69.34)pg/ml vs(202.82± 96.53)pg/ml vs(210.90±84.32)pg/ml].The difference was statistically significant(P<0.05).5 Patients were divided into four groups according to quartiles of distribution range of urinary L-FABP: I group: urinary L-FABP≤23.01μg/g·Cr;Ⅱgroup: urinary L-FABP 23.18~53.26μg/g·Cr;Ⅲgroup: urinary L-FABP 53.62~75.12μg/g·Cr;Ⅳ group: urinary L-FABP≥75.84μg/g·Cr.SBP,CRP,ALB,BUN,SCr,UA,β2-MG,urinary TNF-α,serum TNF-α,serum MCP-1 increased and HGB,Uosm declined.The differences were statistically significant(P﹤0.05).6 86 patients who had renal biopsy reports were divided into two groups according to the area of interstitial fibrosis or renal tubular atrophy in PAS staining.The group A was great than or equal to 5% and the group B was less than 5%.Group A had 58 cases and group B had 28 cases.Between the two groups,SBP,DBP,HGB,ALB,SCr,eGFR,β2-MG,Uosm,urinary L-FABP had differences,whereas CRP,BUN,UA,CHOL,TG,HDL,LDL,FBG,uPRO,serum MCP-1,urinary TNF-α,serum TNF-α had no statistical significance.7 The correlation analysis 7.1 Univariate analysis revealed the following variables to be positively and significantly associated with urinary L-FABP level: BUN,SCr,β2-MG,urinary TNF-α,serum MCP-1.HGB and eGFR were negatively and significantly associated with urinary L-FABP level.Age,SBP,DBP,BMI,CRP,ALB,UA,CHOL,TG,HDL,LDL,FBG,Uosm,uPRO,serum TNF-α were not correlated with urinary L-FABP level.7.2 Univariate analysis revealed the following variables to be positively and significantly associated with urinary TNF-α level: age,SBP,CRP,ALB,BUN,SCr,UA,β2-MG,uPRO,urinary L-FABP.HGB,Uosm and eGFR were negatively and significantly associated with urinary TNF-α level.DBP,BMI,CHOL,TG,HDL,LDL,FBG,serum TNF-α and serum MCP-1 were not correlated with urinary TNF-α level.8 Multiple linear regression analysis 8.1 Urinary L-FABP was taken as a dependent variable.Age,SBP,DBP,BMI,HGB,CRP,ALB,ALT,AST,BUN,SCr,eGFR,UA,β2-MG,CHOL,TG,HDL,LDL,FBG,Uosm,uPRO,urinary TNF-α,serum TNF-α,serum MCP-1 were incorporated into the model as independent variables.The regression model revealed that ALB,eGFR,β2-MG,urinary TNF-α,serum MCP-1 were the independent predictors of urinary L-FABP in CKD patients.8.2 e GFR was taken as a dependent variable.Age,SBP,DBP,BMI,HGB,CRP,ALB,ALT,AST,BUN,SCr,eGFR,UA,β2-MG,CHOL,TG,HDL,LDL,FBG,Uosm,uPRO,urinary TNF-α,serum TNF-α,serum MCP-1,urinary L-FABP were incorporated into the model as independent variables.The regression model revealed that age,SBP,ALB,BUN,β2-MG,HDL,uPRO,urinary L-FABP were the independent predictors of urinary L-FABP in CKD patients.9 The accuracy of urinary L-FABP predicting the progress of kidney function: ROC-AUC of urinary L-FABP was 0.708(95%CI 0.578~0.837,P<0.01),whereas ROC-AUC of uPRO was 0.555(95%CI 0.46~0.65,P<0.01).Urinary L-FABP was superior to uPRO in the accuracy of predicting the progress of kidney function(cut off 39.53μg/g·Cr,sensitivity 82.4%,specificity 55.6%).Conclusions:1 Urinary L-FABP can be an indicator of in early stage of kidney damage.Urinary L-FABP was associated with renal tubular interstitial damage and negatively associated with eGFR.The accuracy of predicting the progress of kidney function was better.2 Urinary TNF-α and serum MCP-1 were the independent predictors of urinary L-FABP in CKD patients.L-FABP possibly played a important role by disturbing the kidney local inflammation reaction.