Relationship Between Urinary Liver-type Fatty Acid Binding Protein And Tubular Interstitial Lesion In IgA Nephropathy

Objective: To observe the changes of urinary liver-type fatty acid binding protein(L-FABP) and oxidation stress index in patients with Ig A nephropathy(Ig AN) after ACEI/ARB treatment, so as to explore the relationship between L-FABP and tubular interstitial lesion(TIL) in Ig AN.Methods: 52 patients with Ig AN diagnosed on clinic and renal biopsy in our hospital 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. All Ig AN patients received ACEI or ARB. Patients’ general situations(including gender, age, blood pressure, etc) were recorded. Serum albumin, alanine aminotransferase, total cholesterol, low density lipoprotein cholesterin, serum creatinine, urea nitrogen, serum uric acid, β2-microglobulin and 24-h urinary protein were also measured before and after 3 and 6 months of treatment, estimated glomerular filtration rate was calculated by CKD-EPI equation. Urinary levels of L-FABP and 8-OHd G were measured by an enzyme-linked immunosorbent assay(ELISA), serum SOD levels were measured by a colorimetry method, urine creatinine levels were measured by a Jaffe’s assay. The results of urinary L-FABP and 8-OHd G had to be divided by urine creatinine values. All the data were processed and analysed by SPSS13.0 software.Results:(1) 52 cases of Ig AN patients, 29 males and 23 females, mean age(38.77±10.08) years; healthy control group: 52 cases of men, 28 males and 24 females, mean age(40.04±11.66) years. There was no significant difference in sex, age, BMI, ALB, ALT, TC, LDL-C between the two groups(P>0.05), whereas SBP, DBP, Scr, BUN, UA, β2-MG, u Pr, the degree of tubular atrophy/interstitial fibrosis were significantly different(P<0.01).(2) Compared with control group, urinary levels of L-FABP(8.88±1.73μg/g.Cr vs 121.86±57.42μg/g.Cr, P<0.01), 8-OHd G(4.46±1.44ng/mg.Cr vs 23.39±8.29 ng/mg.Cr, P<0.01) were significantly higher and serum SOD(149.98±21.38 U/ml vs 86.23±13.42U/ml, P<0.01) was significantly lower in patients with Ig AN.(3) According to the degree of TIL in the Oxford Classification, Ig AN patients were divided into three groups: T0 group, 17 cases, 7 males and 10 females, mean age(31.24±6.65) years; T1 group, 19 cases, 12 males and 7 females, mean age(43.16±9.87) years; T2 group, 16 cases, 10 males and 6 females, mean age(41.56±9.18) years. In T0, T1 and T2 group, u Pr(0.98±0.21g/d vs 2.49±0.86g/d vs 3.67±1.40g/d), urinary levels of L-FABP(58.60±14.84μg/g.Cr vs 131.80±33.43μg/g.Cr vs 177.28±41.19μg/g.Cr), 8-OHd G(14.60±3.49ng/mg.Cr vs 24.52±4.00ng/mg.Cr vs 31.39±6.62 ng/mg.Cr) and serum SOD(100.82±6.99U/ml vs 83.75±7.44U/ml vs 73.65±8.74U/ml) were significantly different(P<0.05), whereas there was no significant difference in sex, BMI, DBP, ALB, ALT, TC among the three groups(P>0.05). Compared with T0 group, SBP, Scr, BUN, UA, β2-MG were significantly higher, e GFR was significantly lower in groups T1 and T2(P<0.05), and LDL-C was also significantly higher in T2 group, which was significantly different(P<0.05). However there was no significant difference in SBP, LDL-C, Scr, BUN, UA, β2-MG, e GFR between T1 and T2 group(P>0.05).(4) The changes of clinical index before and after treatment: at 3 and 6 months, SBP, DBP, LDL-C of Ig AN patients were decreased compared with baseline(P<0.05), ALB, ALT, TC, Scr, BUN, UA, β2-MG, e GFR had no significant changes before and after treatment(P>0.05), whereas at 6 months, u Pr was decreased compared with baseline [1.22(0.44,1.96)g/d vs 2.15(1.14,3.28) g/d, P<0.05].(5) The changes of urinary L-FABP before and after treatment: urinary levels of L-FABP at 3 months(83.64±32.39μg/g.Cr vs 121.86±57.42μg/g.Cr), 6 months(51.02±22.74μg/g.Cr vs 121.86±57.42 μg/g.Cr) were decreased compared with baseline(P<0.05).(6) The changes of urinary 8-OHd G, serum SOD before and after treatment: urinary levels of 8-OHd G at 3 months(15.25±4.32ng/mg.Cr vs 23.39±8.29ng/mg.Cr), 6 months(10.78±3.51ng/mg.Cr vs 23.39±8.29 ng/mg.Cr) were decreased compared with baseline(P<0.05) and serum SOD at 3 months(103.69±15.67U/ml vs 86.23±13.42U/ml), 6 months(121.51±14.01U/ml vs 86.23±13.42 U/ml) were increased compared with baseline(P<0.05).(7) The correlation analysis of urinary L-FABP levels and some clinical data: the levels of urinary L-FABP in Ig AN patients were correlated positively with SBP(r=0.645, P<0.01), DBP(r=0.345, P<0.05), LDL-C(r=0.476, P<0.01), Scr(r=0.751, P<0.01), BUN(r=0.588, P<0.01), UA(r=0.610, P<0.01), β2-MG(r=0.677, P<0.01), u Pr(r=0.962, P<0.01), urinary 8-OHd G(r=0.958, P<0.01), the degree of tubular atrophy/interstitial fibrosis(r=0.866, P<0.01), correlated negatively with serum SOD(r=-0.931, P<0.01), e GFR(r=-0.758, P<0.01), and not correlated with sex, age, BMI, ALB, ALT, TC(P>0.05).(8) The correlation analysis of urinary 8-OHd G levels and some clinical data: the levels of urinary 8-OHd G in Ig AN patients were correlated positively with age(r=0.283, P<0.05), SBP(r=0.602, P<0.01), DBP(r=0.301, P<0.05), LDL-C(r=0.485, P<0.01), Scr(r=0.750, P<0.01), BUN(r=0.609, P<0.01), UA(r=0.609, P<0.01), β2-MG(r=0.630, P<0.01), u Pr(r=0.921, P<0.01), the degree of tubular atrophy/interstitial fibrosis(r=0.856, P<0.01), correlated negatively with serum SOD(r=-0.964, P<0.01), e GFR(r=-0.770, P<0.01), and not correlated with sex, BMI, ALB, ALT, TC(P>0.05).(9) The correlation analysis of serum SOD levels and some clinical data: the levels of serum SOD in Ig AN patients were correlated negatively with age(r=-0.329, P<0.05), SBP(r=-0.596, P<0.01), DBP(r=-0.350, P<0.05), LDL-C(r=-0.480, P<0.01), Scr(r=-0.803, P<0.01), BUN(r=-0.647, P<0.01), UA(r=-0.662, P<0.01), β2-MG(r=-0.665, P<0.01), u Pr(r=-0.908, P<0.01), the degree of tubular atrophy/interstitial fibrosis(r=-0.840, P<0.01), correlated positively with e GFR(r=0.773, P<0.01), and not correlated with sex, BMI, ALB, ALT, TC(P>0.05).(10) Stepwise multiple regression analysis: urinary L-FABP was taken as a dependent variable. SBP, DBP, LDL-C, Scr, BUN, UA, β2-MG, SOD, e GFR, u Pr, urinary 8-OHd G were incorporated into the model as independent variables. The regression model revealed that urinary 8-OHd G(B=3.955, P=0.000) and u Pr(B=17.248, P=0.000) were the independent predictors of urinary L-FABP in Ig AN patients.Conclusions: Urinary levels of L-FABP in patients with Ig AN are elevated with the severity of tubular atrophy/interstitial fibrosis, so it is a TIL biomarker that can be used to monitor the progress of kidney disease and also protects TIL via antioxidant effect.