血清中性粒细胞明胶酶相关脂质运载蛋白、胱抑素C及尿白蛋白肌酐比值、N-乙酰-β-D-氨基葡萄糖苷酶检测在早期糖尿病肾脏疾病中的应用价值
|
摘要
目的探讨血清中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、胱抑素C(Cys-C)及尿白蛋白肌酐比值(UACR)、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)在早期糖尿病肾病(EDN)中的应用价值。方法选取eGFR>60 ml/(min·1.73 m~2)的T2DM患者430例,按UACR水平分为正常蛋白尿组(NA,UACR<30 mg/g)165例、微量蛋白尿组(MA,30≤UACR<300 mg/g)155例及大量蛋白尿组(HA,UACR≥300 mg/g)110例。另选门诊健康体检者175名为正常对照组(NC)。检测各组血NGAL、Cys-C及UACR、NAG水平并行统计学分析。结果与NC组比较,NA组NAG、NGAL升高,MA组NGAL、Cys-C、UACR、NAG也升高(P<0.01)。与NA组比较,MA组NGAL、UACR、NAG升高(P<0.01)。HA组各项指标较其他组升高(P<0.01)。相关性分析显示,UACR与NAG、Cys-C、NGAL均呈正相关(r为0.583、0.569、0.513)。多因素Logistic回归分析显示,Cys-C、UACR是EDN独立的风险因素。UACR、NAG、Cys-C、NGAL的受试者工作特征(ROC)曲线下面积(AUC)依次为0.973、0.864、0.778、0.759,单项检测NAG敏感性最高(90.2%),Cys-C特异性最大(94.5%)。结论 4种标志物与EDN密切相关,Cys-C、UACR是EDN独立的风险因素;NAG是早于尿白蛋白出现的反应肾小管间质损伤非常敏感的指标;NGAL作为一种新型的生物学标志物与EDN的损伤程度密切相关,是糖尿病肾脏疾病(DKD)发生发展重要的动态监测指标。4项指标联合检测的诊断效能最大(敏感性97.4%、特异性98.5%)。
Objective To investigate the application value of serum neutrophil gelatinase-associated lipocalin(NGAL), cystatin C(Cys-C), urinary albumin creatinine rate(UACR) and N-acetyl-β-Dglucosaminidase(NAG) in early diabetic nephropathy. Methods A total of 430 type 2 diabetes mellitus(T2 DM) inpatients with estimated glomerular filtration rate(eGFR) > 60 ml/(min. 1.73 m~2) were divided into groups of normal albumin(NA,n= 165),microalbumin(MA,n= 155),high albumin(HA,n=110). 150 health people were selected as the normal control(NC). All subjects had the detections of serum NGAL,Cys-C, urinary UACR and NAG. Results Compared with NC group, NA group had higher NGA L and NAG levels(P<0. 01),MA group had higher levels of NGAL,Cys-C,UACR and NAG(P<0. 01). Compared with NA group, MA group had higher levels of NGAL,UACR and NAG(P<0. 01). Every index increased in HA group when compared with other 3 groups. Correlation analysis showed that UACR was positively correlated with NAG,Cys-C and NGAL(r=0. 583,0. 569 and 0. 513,respectively). Multiple logistic regression analysis showed that Cys-C and UACR were closely related independent predictor in early diabetic nephropathy. The receiver operator characteristic curve(ROC) area under curve(AUC) of UACR(0. 973) was the biggest, following by NAG(0. 864),Cys-C(0. 778) and NGAL(0. 759). The sensitivity of NAG was the highest(90. 2%),and the specificity of Cys-C was the biggest(94. 5%). Conclusion These four markers were all closely related to early diabetic kidney disease(DKD). Cys-C and UACR were independent risk factors for DKD. NAG is hypersensitive index for early renal tubuloirnterstitial injury and NGAL was hypersensitive and dynamic monitoring indicator in the development of diabetes. The four combined indexes have high diagnostic efficiency with sensitivity97. 4% and specificity 98. 5%.
Objective To investigate the application value of serum neutrophil gelatinase-associated lipocalin(NGAL), cystatin C(Cys-C), urinary albumin creatinine rate(UACR) and N-acetyl-β-Dglucosaminidase(NAG) in early diabetic nephropathy. Methods A total of 430 type 2 diabetes mellitus(T2 DM) inpatients with estimated glomerular filtration rate(eGFR) > 60 ml/(min. 1.73 m~2) were divided into groups of normal albumin(NA,n= 165),microalbumin(MA,n= 155),high albumin(HA,n=110). 150 health people were selected as the normal control(NC). All subjects had the detections of serum NGAL,Cys-C, urinary UACR and NAG. Results Compared with NC group, NA group had higher NGA L and NAG levels(P<0. 01),MA group had higher levels of NGAL,Cys-C,UACR and NAG(P<0. 01). Compared with NA group, MA group had higher levels of NGAL,UACR and NAG(P<0. 01). Every index increased in HA group when compared with other 3 groups. Correlation analysis showed that UACR was positively correlated with NAG,Cys-C and NGAL(r=0. 583,0. 569 and 0. 513,respectively). Multiple logistic regression analysis showed that Cys-C and UACR were closely related independent predictor in early diabetic nephropathy. The receiver operator characteristic curve(ROC) area under curve(AUC) of UACR(0. 973) was the biggest, following by NAG(0. 864),Cys-C(0. 778) and NGAL(0. 759). The sensitivity of NAG was the highest(90. 2%),and the specificity of Cys-C was the biggest(94. 5%). Conclusion These four markers were all closely related to early diabetic kidney disease(DKD). Cys-C and UACR were independent risk factors for DKD. NAG is hypersensitive index for early renal tubuloirnterstitial injury and NGAL was hypersensitive and dynamic monitoring indicator in the development of diabetes. The four combined indexes have high diagnostic efficiency with sensitivity97. 4% and specificity 98. 5%.
引文
[1]Zhang L,Wang H,Long J,et al.Trends in chronic kidney dis-ease in china.N Engl J Med,2016,375:905-906.
[2]Mogensen CE,Christensen CK,Vittinghus E.The stages in diabetic renal disease,with emphasis on the stages of incipient diabetic nephropathy.Diabetes,1983,32:64-78.
[3]Tang SC,Leung JC,Lai KN.Diabetic tubulopathy:an emerging entity.Contrib Nephrol,2011,170:124-134.
[4]National Kidney Foundation.KDOQI clinical practice guideline for diabetes and CKD:2012 Update.Am J Kidney Dis,2012,60:850-886.
[5]National Kidney Foundation.K/DOQI clinical practice quidelines and clinical recommendations for diabetes and chronic kidney disease.Am J Kidney Dis,2007,49:S12-S154.
[6]程苏琴,朱美财.尿微量白蛋白在糖尿病肾损伤早期诊断中的价值.中华检验医学杂志,2005,28:740-741.
[7]De Jong PE,Curhan GC.Screening,monitoring,and treatment of albuminuria:Public health perspectives.J Am Soc Nephrol,2006,17:2120-2126.
[8]Singh D,Whooley MA,Lx JH,et al.Association of cystatin C and estimated GFR with inflammatory biomarkers:the heart and soul study.Nephrol Dial Transplant,2007,22:1087-1092.
[9]Inker LA,Schmid CH,Tighiouart H,et al.Estimating glomerular filtration rate from serum creatinine and cystatin C.N Engl J Med,2012,367:20-29.
[10]Shlipak MG,Mattes MD.Peralta CA.Update on cystatin C:incorporation inton clinical practice.Am J Kidney Dis,2013,27:1050-1053.
[11]童俊容,何凤,张虹,等.糖尿病肾病患者尿液中性粒细胞明胶酶相关脂质运载蛋白及肾损伤分子-1水平变化及意义.中国全科医学,2012,15:2785-2787.
[12]崔丽艳,张捷.中性粒细胞明胶酶相关脂质运载蛋白与肾脏疾病.中华检验医学杂志,2011,34:85.
[13]Singer E,Marko L,paragas N,et al.Neutrophil gelatinase-associated lipocalin:pathophysiology and clinical applications.Acta Physiol(Oxf),2013,207:663-672.
[14]Bolignano D,Lacquaniti A,Coppolino G,et al.Neutrophil gelatinase-associated lipocalin as an early biomarker of nephropathy in diabetic patients.Kidney Blood Press Res,2009,32:91-98.
[15]王依屹,张珏,鲁传翠,等.血清NGAL、Cys-C、和尿NAG联合检测在糖尿病肾病诊断中的临床意义.检验医学,2015,30:1096-1099.
[16]Bolignano D,Lacpuaniti A,Coppolino G,et al.Neutrophil gelatinase-associated lipocalin as an early biomarker of nephropathy in diabetic patients.Kidney Blood Press Res,2009,32:91-98.
[17]Tang SC,Lai KN.The pathogenic role of the renal proximal tubular cell in diabetic nephropathy.Nephrol Dial Transplant,2012,27:3049-3056.
[18]Udomah FP,Ekrikpo U,Effa E,et al.Association between urinary N-acetyl-β-D-glucosaminidase and microalbuminuria in diabetic black Africans.Int J Nephrol,2012,2012:234-235.
[19]张晓青,宗成国,栾旭华,等.尿mAlb/Cr、NAG,、LAP检测对早期糖尿病肾病的诊断价值.中国现代医学杂志,2009,19:122-124.
[2]Mogensen CE,Christensen CK,Vittinghus E.The stages in diabetic renal disease,with emphasis on the stages of incipient diabetic nephropathy.Diabetes,1983,32:64-78.
[3]Tang SC,Leung JC,Lai KN.Diabetic tubulopathy:an emerging entity.Contrib Nephrol,2011,170:124-134.
[4]National Kidney Foundation.KDOQI clinical practice guideline for diabetes and CKD:2012 Update.Am J Kidney Dis,2012,60:850-886.
[5]National Kidney Foundation.K/DOQI clinical practice quidelines and clinical recommendations for diabetes and chronic kidney disease.Am J Kidney Dis,2007,49:S12-S154.
[6]程苏琴,朱美财.尿微量白蛋白在糖尿病肾损伤早期诊断中的价值.中华检验医学杂志,2005,28:740-741.
[7]De Jong PE,Curhan GC.Screening,monitoring,and treatment of albuminuria:Public health perspectives.J Am Soc Nephrol,2006,17:2120-2126.
[8]Singh D,Whooley MA,Lx JH,et al.Association of cystatin C and estimated GFR with inflammatory biomarkers:the heart and soul study.Nephrol Dial Transplant,2007,22:1087-1092.
[9]Inker LA,Schmid CH,Tighiouart H,et al.Estimating glomerular filtration rate from serum creatinine and cystatin C.N Engl J Med,2012,367:20-29.
[10]Shlipak MG,Mattes MD.Peralta CA.Update on cystatin C:incorporation inton clinical practice.Am J Kidney Dis,2013,27:1050-1053.
[11]童俊容,何凤,张虹,等.糖尿病肾病患者尿液中性粒细胞明胶酶相关脂质运载蛋白及肾损伤分子-1水平变化及意义.中国全科医学,2012,15:2785-2787.
[12]崔丽艳,张捷.中性粒细胞明胶酶相关脂质运载蛋白与肾脏疾病.中华检验医学杂志,2011,34:85.
[13]Singer E,Marko L,paragas N,et al.Neutrophil gelatinase-associated lipocalin:pathophysiology and clinical applications.Acta Physiol(Oxf),2013,207:663-672.
[14]Bolignano D,Lacquaniti A,Coppolino G,et al.Neutrophil gelatinase-associated lipocalin as an early biomarker of nephropathy in diabetic patients.Kidney Blood Press Res,2009,32:91-98.
[15]王依屹,张珏,鲁传翠,等.血清NGAL、Cys-C、和尿NAG联合检测在糖尿病肾病诊断中的临床意义.检验医学,2015,30:1096-1099.
[16]Bolignano D,Lacpuaniti A,Coppolino G,et al.Neutrophil gelatinase-associated lipocalin as an early biomarker of nephropathy in diabetic patients.Kidney Blood Press Res,2009,32:91-98.
[17]Tang SC,Lai KN.The pathogenic role of the renal proximal tubular cell in diabetic nephropathy.Nephrol Dial Transplant,2012,27:3049-3056.
[18]Udomah FP,Ekrikpo U,Effa E,et al.Association between urinary N-acetyl-β-D-glucosaminidase and microalbuminuria in diabetic black Africans.Int J Nephrol,2012,2012:234-235.
[19]张晓青,宗成国,栾旭华,等.尿mAlb/Cr、NAG,、LAP检测对早期糖尿病肾病的诊断价值.中国现代医学杂志,2009,19:122-124.