| Objective:To test the changes of urinary and local tissues liver-type fatty acid binding protein(L-FABP)and angiotensin?(Ang?),explore the role and potential mechanism of L-FABP in IgAN,especially tubular interstitial lesion(TIL).Methods:37 patients with IgAN diagnosed on clinic and renal biopsy in our hospital between September 2014 and June 2015 were enrolled,they were divided into three groups according to the degree of TIL in the Oxford Classification: T0 group(tubular atrophy/interstitial fibrosis<25%),T1 group(tubular atrophy/interstitial fibrosis 25%~50%),T2 group(tubular atrophy/interstitial fibrosis>50%).52 cases of age and sex-matched healthy controls.Patients' general situations(including gender,age,BMI,etc)were recorded.Serum albumin(ALB),alanine aminotransferase(ALT),total cholesterol(TC),low density lipoprotein cholesterin(LDL-C),serum creatinine(Scr),urea nitrogen(BUN),?2-microglobulin(?2-MG),serum uric acid(UA)and 24-h urinary protein(uPr)were also measured,estimated glomerular filtration rate(e GFR)was calculated by CKD-EPI equation.Urinary levels of L-FABP and Ang ?were measured by an enzyme-linked immunosorbent assay(ELISA),and the correction of urine creatinine values.Intrarenal L-FABP and Ang ?dyeing with immunohistochemical,and semi-quantitative analysis using image analysis software.All the data were processed and analysed by SPSS16.0 software.Results:1 general case:37 cases of IgAN patients in experimental group,24 males and 13 females,mean age(39.57±10.31)years;healthy control group: 37 cases of men,21 males and 16 females,mean age(41.41±11.94)years.There was no significant difference in Sex,Age,BMI,ALT,TC and LDL-C between the two groups(P>0.05),whereas SBP,DBP,Scr,BUN,UA,?2-MG,uPr,TIL were significantly higher and ALB,eGFR were significantly lower in patients with IgAN,which was significantly different(P<0.01).2 In IgAN group:1)In T0,T1 and T2 group,Scr,uPr,the degree of TIL,uL-FABP,uAng?and eGFR were significantly different(P<0.05),whereas there was no significant difference in Sex,BMI,ALT,TC among the three groups(P>0.05);2)Compared with T0 group,Age,SBP,DBP,BUN,UA,?2-MG were significantly higher lower in groups T1 and T2(P<0.05).Then LDL-C was significantly higher,and ALB was significantly lower in T2 group,which was significantly different(P<0.05).However there was no significant difference in Age,SBP,DBP,BUN,UA,?2-MG between T1 and T2 group(P>0.05).3 Expression level of L-FABP: 1)Compared with control group,urinary levels of L-FABP(112.42±51.65ng/mg.Cr vs 9.31±1.66ng/mg.Cr)were significantly higher in patients with IgAN,which was significantly different(P<0.01);In T0,T1 and T2 group,urine level of L-FABP(52.08±12.44ng/mg.Cr vs 125.51±36.58ng/mg.Cr vs 157.84±34.94ng/mg.Cr)are elevated with the severity of TIL,both two are statistically significant(P<0.01);2)Renal tissue L-FABP(rL-FABP)immunohistochemical staining:L-FABP was diffusely expressed throughout the proximal tubules,mainly in the cytoplasma and nucleus of the tubular epithelial cells,and L-FABP staining positive area is increased and the chroma deepened with the severity of TIL.The semi-quantitative analysis show that,T0,T1 and T2,three groups of rL-FABP average optical density(AOD)(0.145±0.004 vs 0.224±0.042 vs 0.528±0.067)progressive increase,the difference was statistically significant(P< 0.01).4 Expression level of Ang?: 1)Compared with control group,urinary levels of Ang ?(6391.3±2274.6ng/mg.Cr vs 995.58±119.58ng/mg.Cr)were significantly higher in patients with IgAN,which was significantly different(P<0.01);In T0,T1 and T2 group,urine level of Ang?(3466.20±947.19ng/mg.Cr vs 6775.40±756.29ng/mg.Cr vs 8994.30±705.67ng/mg.Cr)are elevated with the severity of TIL,both two are statistically significant(P<0.01);2)Renal tissue Ang?(r Ang?)immunohistochemical staining:Ang?was diffusely expressed throughout the proximal tubules,mainly in the cytoplasma of the tubular epithelial cells,glomerular mesangial cells and endothelial cell cytoplasm,small blood vessels are some expression,and Ang staining positive area is increased and ?the chroma deepened with the severity of TIL.The semi-quantitative analysis show that,T0,T1 and T2,three groups of rAng ?average optical density(AOD)(0.253±0.039 vs 0.502±0.093 vs 0.855±0.091)progressive increase,the difference was statistically significant(P< 0.01).5 Correlation analysis data: 1)The correlation analysis of urinary L-FABP levels and some clinical data: the levels of urinary L-FABP in IgAN patients were correlated positively with SBP(r=0.589,P<0.01),DBP(r=0.555,P<0.01),LDL-C(r=0.541,P<0.01),Scr(r=0.695,P<0.01),BUN(r=0.588,P <0.01),UA(r=0.613,P<0.01),?2-MG(r=0.592,P<0.01),uPr(r=0.888,P<0.01),the degree of TIL(r=0.772,P<0.01),uAng?(r=0.831,P<0.01),rL-FABP(AOD)(r=0.630,P<0.05),rAng?(AOD)(r=0.570,P<0.05),correlated negatively with eGFR(r=-0.687,P<0.01),and not correlated with Sex,Age,BMI,ALB,ALT,TC(P>0.05).2)The correlation analysis of renal tissue L-FABP levels and some clinical data: the levels of renal tissue L-FABP in IgAN patients were correlated positively with Scr(r=0.717,P<0.01),BUN(r=0.621,P<0.05),UA(r=0.574,P<0.05),uPr(r=0.564,P<0.05),the degree of TIL(r=0.781,P<0.01),r Ang?(AOD)(r=0.928,P<0.01),correlated negatively with eGFR(r=-0.801,P<0.01),and not correlated with Sex,Age,BMI,SBP,DBP,ALB,ALT,TC,LDL-C,?2-MG(P>0.05).3)The correlation analysis of urinary Ang levels and some clinical data: the levels of urinary ?Ang ?in IgAN patients were correlated positively with Age(r=0.501,P<0.01),SBP(r=0.481,P<0.01),DBP(r=0.454,P<0.01),LDL-C(r=0.539,P<0.01),Scr(r=0.749,P<0.01),BUN(r=0.721,P<0.01),UA(r=0.632,P<0.01),?2-MG(r=0.530,P<0.01),uPr(r=0.716,P<0.01),the degree of TIL(r=0.913,P<0.01),uL-FABP(r=0.831,P<0.01),rL-FABP(AOD)(r=0.728,P<0.01),rAng?(AOD)(r=0.696,P<0.01),correlated negatively with ALB(r=-0.408,P<0.05),eGFR(r=-0.842,P<0.01),and not correlated with Sex,BMI,ALT,TC(P>0.05).4)The correlation analysis of renal tissue Ang ?levels and some clinical data: the levels of renal tissue Ang in IgAN patients ?were correlated positively with Scr(r=0.560,P<0.05),UA(r=0.497,P<0.01),the degree of TIL(r=0.680,P<0.01),rL-FABP(AOD)(r=0.928,P<0.01),correlated negatively with ALB(r=-0.517,P<0.05),eGFR(r=-0.764,P<0.01),and not correlated with Sex,Age,BMI,SBP,DBP,ALT,TC,LDL-C,BUN,?2-MG,uPr(P>0.05).6 Stepwise multiple regression analysis: 1)Urinary L-FABP was taken as a dependent variable.After eliminating confounding factors,the regression model revealed that u Pr(B=49.58,P=0.000)were the independent predictors of urinary L-FABP in IgAN patients.2)Renal tissue L-FABP was taken as a dependent variable.After eliminating confounding factors,the regression model revealed that rAng?(B=0.496,P=0.000),Scr(B=0.03,P=0.01)were the independent factors of rL-FABP in IgAN patients.3)TIL was taken as a dependent variable.After eliminating confounding factors,the regression model revealed that uL-FABP(B=0.150,P=0.002),rL-FABP(B=33.621,P=0.021),uAng?(B=0.007,P=0.000),rAng?(B=18.971,P=0.03)were the independent predictors of TIL in IgAN patients.Conclusions:1 The urinary and renal tissue L-FABP are independent predictors of tubulointerstitial lesions(TIL)in IgA nephropathy(IgAN).2 The level of urinary L-FABP is a reliable biomarker for evaluation of renal tissue L-FABP in IgAN patients.3 In IgAN patients,urinary Ang?is a valid index to evaluate RAS activation.4 The renal local Ang? level is the independent factors of renal tissue L-FABP in IgAN. |
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