尿视黄醇结合蛋白、尿肝型脂肪酸结合蛋白、血成纤维细胞生长因子-21、血转化生长因子-β联合诊断早期糖尿病肾病的价值

    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

      摘要
    • 摘要: 目的分析尿视黄醇结合蛋白(retinol binding protein,RBP)、尿肝型脂肪酸结合蛋白(liver type fatty acid binding protein,L-FABP)、血成纤维细胞生长因子-21(fibroblast growth factor-21,FGF-21)、转化生长因子-β(transforming growth factor-β,TGF-β)联合诊断早期糖尿病肾病(diabetic nephropathy,DN)的价值。方法选取2019年3月至2020年2月到咸宁市中心医院就诊的2型糖尿病(type 2 diabetes mellitus,T2DM)患者129例,根据尿微量白蛋白/肌酐(urinary albumin/creatinine,UA/CR)比值将所有患者分为DM对照组(n=48)、DN微量蛋白尿组(n=43)及DN大量蛋白尿组(n=38)3组;同期选择于我院体检的39名健康人作为正常对照组。采用免疫比浊法测定各组受检者尿RBP、尿微量白蛋白(microalbumin,mAlb)水平;采用酶联免疫法测定各组受检者尿L-FABP水平,采用酶联免疫法检测各组受检者血FGF-21、TGF-β、三酰甘油(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白-胆固醇(high density lipoprotein-cholesterol,HDL-C)、低密度脂蛋白-胆固醇(low density lipoprotein-cholesterol,LDL-C)水平;采用全自动生化检测仪检测各组受检者血清空腹血糖(fasting plasma glucose,FPG)、餐后2 h血糖、平均血糖、24 h尿蛋白定量(24 h urinary protein,24 h UP)、糖化血红蛋白(haemoglobin A1c,HbA1c)、血清白蛋白、血红蛋白(hemoglobin,Hb)、血肌酐(serum creatinine,Scr)、血尿素氮(blood urea nitrogen,BUN)、血尿酸(serum uric acid,SUA)水平;采用改良MDRD方程计算肾小球滤过率(glomerular filtration rate,GFR)。采用Pearson相关性分析尿RBP、尿L-FABP、血FGF-21以及血TGF-2与肾功能的关系。采用受试者工作特征曲线(receiver operator characteristic curve,ROC)曲线分析尿RBP、尿L-FABP、血FGF-21、血TGF-β与四者联合在诊断DN中的价值。结果 DM对照组、DN微量蛋白尿组及DN大量蛋白尿组的尿RBP(56.32±6.24)mg/L、(78.86±14.22) mg/L、(103.25±16.57) mg/L比(37.33±5.13) mg/L、尿L-FABP(39.56±4.51) μg/g、(89.69±11.88) μg/g、(196.38±36.21) μg/g比(13.45±1.33) μg/g、血FGF-21(254.85±25.19)μg/L、(305.42±30.36)μg/L、(354.12±35.67)μg/L比(209.36±19.32)μg/L及血TGF-β(427.36±43.74)ng/L、(543.89±63.45)ng/L、(672.13±82.16)ng/L比(356.24±39.15)ng/L水平均明显高于正常对照组(P<0.05);DM对照组、DN微量蛋白尿组及DN大量蛋白尿组的Scr(62.35±18.51) μmol/L、(68.52±27.96) μmol/L、(127.94±109.60) μmol/L比(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比(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比(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比(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比(3.54±1.02)μg/L、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)-1比(113.51±24.87)mL·min-1·(1.73m2)-1水平与正常对照组相比,均明显增高(P<0.05);DM对照组、DN微量蛋白尿组及DN大量蛋白尿组FPG(8.87±3.43)mmol/L、(9.74±4.29)mmol/L、(9.35±3.96)mmol/L比(5.21±0.43)mmol/L、餐后2 h血糖(12.42±5.31)mmol/L、(14.86±4.75)mmol/L、(13.71±5.43)mmol/L比(6.12±1.05)mmol/L、平均血糖(12.14±4.47)mmol/L、(13.38±4.62)mmol/L、(12.87±4.36) mmol/L比(5.22±0.21) mmol/L、HbA1c(8.41±2.31)%、(8.84±2.35)%、(8.76±3.08)%比(5.63±2.02)%均明显高于正常对照组(P<0.05);DM对照组、DN微量蛋白尿组及DN大量蛋白尿组TG(1.26±0.88)mmol/L、(1.48±0.11)mmol/L、(1.71±0.09)mmol/L比(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比(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比(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比(2.76±0.33)mmol/L、血清白蛋白(42.49±3.96)g/L、(39.64±4.45)g/L、(37.82±4.94)g/L比(39.51±3.08)g/L水平均明显高于正常对照组(P<0.05),Hb(129.12±16.23)g/L、(126.33±19.45)g/L、(117.72±24.93)g/L比(134.22±10.13)g/L水平均明显低于正常对照组(P<0.05)。Pearson相关性分析可得,尿RBP、血FGF-21、血TGF-β与Scr、BUN、SUA、24 h UP、mAlb、eGFR呈显著正相关(P<0.05),尿L-FABP与Scr、BUN无明显相关(P>0.05),与SUA、24 h UP、mAlb、eGFR呈显著正相关(P<0.05)。ROC曲线分析得知,尿RBP、尿L-FABP、血FGF-21、血TGF-β单独诊断DN的曲线下面积(area under curve,AUC)分别为0.725、0.756、0.749、0.715,四者联合诊断的DN的AUC为0.901。结论 DN患者尿RBP、尿L-FABP、血FGF-21及血TGF-β表达水平明显异常,四者联合应用对早期DN具有显著的诊断价值。

       

      Abstract: 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.

       

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