Value of urinary retinol binding protein,urinary hepatic fatty acid binding protein,serum fibroblast growth factor-21 and transforming growth factor-β in the diagnosis of early diabetic nephropathy

Objective To explore the value of urinary retinol binding protein(RBP),urinary hepatic fatty acid binding protein(L-FABP),serum fibroblast growth factor-21(FGF-21)and transforming growth factor-β(TGF-β)in the diagnosis of early diabetic nephropathy(DN).Methods From March2019 to February 2020,129 hospitalized patients with type 2 diabetes mellitus(T2DM)were divided into three groups of DM control(n=48),DN microalbuminuria(n=43)and DN massive proteinuria(n=38)according to urinary microalbumin/creatinine(UACR)ratio. In the same period,39 healthy subjects receiving physical examination were selected as normal control group. Urinary levels of RBP and microalbumin(mAlb)were measured by immunoturbidimetry;urinary levels of L-FABP and serum levels of FGF-21and TGF by enzyme-linked immunosorbent assay(ELISA). Triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C);serum levels of fasting blood glucose(FPG),2-hour postprandial blood glucose,mean blood glucose,24-hour urinary protein(24 h UP),glycosylated hemoglobin(HbA1c),albumin,hemoglobin(Hb),serum creatinine(Scr),urea nitrogen(BUN)and serum uric acid(SUA)were measured by an automatic biochemical detector. Glomerular filtration rate(GFR)was calculated by modified MDRD equation. Pearson's correlation was employed for examining the relationship between urinary RBP,urinary L-FABP,blood FGF-21and blood TGF-2 and renal function. The value of combining urinary RBP,urinary L-FABP,blood FGF-21 and TGF-β in the diagnosis of DN were analyzed by receiver operator characteristic(ROC curve).Results Urinary RBP(56.32±6.24) mg/L,(78.86±14.22) mg/L,(103.25±16.57) mg/L vs(37.33±5.13) mg/L,urinary L-FABP(39.56±4.51) μg/g,(89.69±11.88) μg/g,(196.38±36.21)μg/g vs(13.45±1.33)μg/g,blood FGF-21(254.85±25.19)μg/L,(305.42±30.36)μg/L,(354.12±35.67)μg/L vs(209.36±19.32)μg/Land TGF- β(427.36±43.74)ng/L,(543.89±63.45)ng/L,(672.13±82.16)ng/L vs(356.24±39.15)ng/Lin DM control,DN microalbuminuria and DN macroalbuminuria groups. The levels were significantly higher than those in normal control group(P<0.05). Compared with normal control group,the levels of Scr(62.35±18.51)μmol/L,(68.52±27.96)μmol/L,(127.94±109.60)μmol/L vs(67.89±11.54)μmol/L,BUN(6.01±2.43)mmol/L,(6.37±2.16)mmol/L,(9.65±4.18)mmol/L vs(4.16±0.42)mmol/L,SUA(356.69±34.51)mmol/L,(359.23±36.42)mmol/L,(364.56±41.43)mmol/L vs(288.91±25.77)mmol/L,24 h UP(0.05±0.25)g/24h,(0.36±0.26)g/24h,(0.77±0.28)g/24h vs(0.03±0.17)g/24h,mAlb(6.94±1.63)μg/L,(8.32±1.75)μg/L,(10.46±1.91)μg/L vs(3.54±1.02)μg/Land eGFR(139.65±51.24) mL·min^-1·(1.73m²)^-1,(134.25±63.81) mL·min^-1·(1.73m²)^-1,(86.99±56.76)mL·min^-1·(1.73m²)^-1vs(113.51±24.87)mL·min^-1·(1.73m²)^-1were significantly higher in DM control,DN microalbuminuria and DN macroalbuminuria groups(P<0.05). Blood glucose related parameters were significantly higher in DM control,DN microalbuminuria and DN massive proteinuria groups than those in normal control group(P<0.05). The levels of TG(1.26±0.88)mmol/L,(1.48±0.11)mmol/L,(1.71±0.09)mmol/L vs(0.93±0.97)mmol/L,TC(4.67±0.49)mmol/L,(5.23±0.53)mmol/L,(6.81±0.61)mmol/L vs(3.41±0.33)mmol/L,HDL-C(1.19±0.27)mmol/L,(1.26±0.33)mmol/L,(1.42±0.54)mmol/L vs(1.67±0.23)mmol/L,LDL-C(2.41±0.66)mmol/L,(2.53±0.81)mmol/L,(3.21±1.27)mmol/L vs(2.76±0.33)mmol/L,serum albumin(42.49±3.96) g/L,(39.64±4.45) g/L,(37.82±4.94) g/L vs (39.51±3.08) g/L and Hb(129.12±16.23)g/L,(126.33±19.45)g/L,(117.72±24.93)g/L vs(134.22±10.13)g/Lwere significantly higher in DM control,DN microalbuminuria and DN macroalbuminuria groups than those in normal control group(P<0.05)and the levels of Hb were significantly lower than those in normal control group(P<0.05). Pearson's correlation analysis indicated that urinary RBP,blood FGF-21 and TGF- βwere significant positively correlated with urinary L-FABP and Scr,BUN,SUA,24 h UP,mAlb and eGFR(P<0.05). ROC curve analysis revealed that AUC for urinary RBP,urinary L-FABP,blood FGF-21 and blood TGF-β diagnosing DN alone was 0.725,0.756,0.749 and 0.715 and diagnosing DN jointly 0.901.Conclusion The levels of urinary RBP,urinary L-FABP,serum FGF-21 and TGF-β are abnormal in DN patients. The combined application of the four factors has significant diagnostic value for early DN.