尿中性粒细胞明胶酶相关脂质运载蛋白/肌酐比值在2型糖尿病肾损伤的早期诊断及病情评估中的临床应用
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摘要
目的:探讨尿中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)/肌酐比值在2型糖尿病患者肾脏损伤的早期诊断及病情评估中的临床应用价值。方法:纳入2型糖尿病患者112例,根据尿白蛋白/肌酐比值(urinary albumin/creatinine ratio,UACR)将患者分为尿白蛋白正常(normo-albuminuria, NA)组(38例)、微量白蛋白尿(micro-albuminuria, MA)组(36例)及临床白蛋白尿(clinical albuminuria, CA)组(38例),并以同期32例健康体检者作为正常对照。采用化学发光微粒子免疫检测法测定各组的尿NGAL浓度,并计算尿NGAL/肌酐比值。比较正常对照组及2型糖尿病各组的尿NGAL水平,并与其他临床指标作相关性分析。结果:2型糖尿病各组的尿NGAL/肌酐比值均明显高于正常对照组[正常对照组,9.13(3.92～17.36) ng/mg;NA组,16.46(6.94～27.07) ng/mg;MA组,20.16(6.76～44.35) ng/mg;CA组,26.89(10.60～56.94) ng/mg](P<0.05),而在2型糖尿病各组间,CA组、MA组的NGAL/肌酐比值明显高于NA组(P<0.05)。相关性分析显示,尿NGAL/肌酐比值与UACR、糖尿病病程、糖化血红蛋白(glycated hemoglobin, HbA1c)呈正相关(P<0.05)。结论 :与尿微量白蛋白相比,尿NGAL/肌酐比值可能较更早提示2型糖尿病患者的肾脏损伤,并可在一定程度上评估其疾病严重程度。
Objective:To investigate the application of urinary neutrophil gelatinase associated lipocalin(NGAL)/crea-tinineratio in the early diagnosis and assessment of severity of renal injury in patients with type 2 diabetes mellitus(T2 DM). Methods: A group of 112 T2 DM patients were recruited. Based on urinary albumin/creatinine ratio(UACR), diabetic patients were divided into three groups: 38 cases with normal albuminuria(NA group), 36 cases with minimal albu-minuria(MA group) and 38 cases with clinical albuminuria(CA group). And, 32 healthy subjects were served as controls(NC group). Urinary NGAL/creatinine ratio was calculated and compared among the groups and their correlations with other clinical parameters were analyzed. Results: Urinary NGAL/creatinine ratio in T2 DM groups [NA, 16.46(6.94-27.07) ng/mg;MA, 20.16(6.76-44.35) ng/mg;CA, 26.89(10.60-56.94) ng/mg] was markedly increased than that in the normal control group [9.13(3.92-17.36) ng/mg](P<0.05). In the T2 DM groups, urinary NGAL/creatinine ratio in CA group was significantly higher than that in NA group(P<0.05). Correlation analysis showed that urinary NGAL/creatinine ratio was positively correlated with UACR, duration of diabetes and glycated hemoglobin(HbA1 c)(P<0.05). Conclusions: Urinary NGAL could be an earlier marker than minimal albuminuria for detecting renal injury in T2 DM. Furthermore, urinary NGAL level can evaluate the severity of renal injury.
Objective:To investigate the application of urinary neutrophil gelatinase associated lipocalin(NGAL)/crea-tinineratio in the early diagnosis and assessment of severity of renal injury in patients with type 2 diabetes mellitus(T2 DM). Methods: A group of 112 T2 DM patients were recruited. Based on urinary albumin/creatinine ratio(UACR), diabetic patients were divided into three groups: 38 cases with normal albuminuria(NA group), 36 cases with minimal albu-minuria(MA group) and 38 cases with clinical albuminuria(CA group). And, 32 healthy subjects were served as controls(NC group). Urinary NGAL/creatinine ratio was calculated and compared among the groups and their correlations with other clinical parameters were analyzed. Results: Urinary NGAL/creatinine ratio in T2 DM groups [NA, 16.46(6.94-27.07) ng/mg;MA, 20.16(6.76-44.35) ng/mg;CA, 26.89(10.60-56.94) ng/mg] was markedly increased than that in the normal control group [9.13(3.92-17.36) ng/mg](P<0.05). In the T2 DM groups, urinary NGAL/creatinine ratio in CA group was significantly higher than that in NA group(P<0.05). Correlation analysis showed that urinary NGAL/creatinine ratio was positively correlated with UACR, duration of diabetes and glycated hemoglobin(HbA1 c)(P<0.05). Conclusions: Urinary NGAL could be an earlier marker than minimal albuminuria for detecting renal injury in T2 DM. Furthermore, urinary NGAL level can evaluate the severity of renal injury.
引文
[1] Huang YM, Xu D, Long J, et al. The spectrum of chronic kidney disease in China:a national study based on hospitalized patients from 2010 to 2015[J/OL]. Nephrology(Carlton),2018-08-09[2018-12-19].https://www.ncbi.nlm.nih.gov/pubmed/30198082.
[2] Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic kidney disease:a report from an ADA Consensus Conference[J].Diabetes Care,2014,37(10):2864-2683.
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[4]张春雷,曾学辉,李忠新,等.尿KIM-1和NGAL在糖尿病肾病早期诊断中的应用[J].现代检验医学杂志,2015,30(1):52-54.
[5] Retnakaran R, Cull CA, Thorne KI,et al. Risk factors for renal dysfunction in type 2 diabetes:U.K. Prospective Diabetes Study 74[J]. Diabetes,2006,55(6):1832-1839.
[6] Satirapoj B. Tubulointerstitial Biomarkers for Diabetic Nephropathy[J]. J Diabetes Res,2018,2018:2852398.
[7] Yaqoob M, McClelland P, Patrick AW, et al. Evidence of oxidant injury and tubular damage in early diabetic nephropathy[J]. QJM,1994,87(10):601-607.
[8] Buonafine M, Martinez-Martinez E, Jaisser F. More than a simple biomarker:the role of NGAL in cardiovascular and renal diseases[J]. Clin Sci(Lond),2018,132(9):909-923.
[9] Lippi G, Cervellin G. Neutrophil gelatinase-associated lipocalin:a more specific assay is needed for diagnosing renal injury[J]. Clin Chim Acta,2012,413(13-14):1160-1161.
[10] Shang W, Wang Z. The Update of NGAL in Acute Kidney Injury[J]. Curr Protein Pept Sci,2017,18(12):1211-1217.
[11] Wu J, Shao X, Lu K, et al. Urinary RBP and NGAL Levels are Associated with Nephropathy in Patients with Type2 Diabetes[J]. Cell Physiol Biochem,2017,42(2):594-602.
[12] Wu J, Ding Y, Zhu C, et al. Urinary TNF-αand NGAL are correlated with the progression of nephropathy in patients with type 2 diabetes[J]. Exp Ther Med,2013,6(6):1482-1488.
[13] Bolignano D, Lacquaniti A, Coppolino G, et al. Neutrophil gelatinase-associated lipocalin as an early biomarker of nephropathy in diabetic patients[J]. Kidney Blood Press Res,2009,32(2):91-98.
[14] Yang YH, He XJ, Chen SR, et al. Changes of serum and urine neutrophil gelatinase-associated lipocalin in type-2diabetic patients with nephropathy:one year observational follow-up study[J]. Endocrine,2009,36(1):45-51.
[15] Fu WJ, Xiong SL, Fang YG, et al. Urinary tubular biomarkers in short-term type 2 diabetes mellitus patients:a cross-sectional study[J]. Endocrine,2012,41(1):82-88.
[2] Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic kidney disease:a report from an ADA Consensus Conference[J].Diabetes Care,2014,37(10):2864-2683.
[3]中华医学会糖尿病学分会微血管并发症学组.糖尿病肾病防治专家共识(2014年版)[J].中华糖尿病杂志,2014,6(11):792-801.
[4]张春雷,曾学辉,李忠新,等.尿KIM-1和NGAL在糖尿病肾病早期诊断中的应用[J].现代检验医学杂志,2015,30(1):52-54.
[5] Retnakaran R, Cull CA, Thorne KI,et al. Risk factors for renal dysfunction in type 2 diabetes:U.K. Prospective Diabetes Study 74[J]. Diabetes,2006,55(6):1832-1839.
[6] Satirapoj B. Tubulointerstitial Biomarkers for Diabetic Nephropathy[J]. J Diabetes Res,2018,2018:2852398.
[7] Yaqoob M, McClelland P, Patrick AW, et al. Evidence of oxidant injury and tubular damage in early diabetic nephropathy[J]. QJM,1994,87(10):601-607.
[8] Buonafine M, Martinez-Martinez E, Jaisser F. More than a simple biomarker:the role of NGAL in cardiovascular and renal diseases[J]. Clin Sci(Lond),2018,132(9):909-923.
[9] Lippi G, Cervellin G. Neutrophil gelatinase-associated lipocalin:a more specific assay is needed for diagnosing renal injury[J]. Clin Chim Acta,2012,413(13-14):1160-1161.
[10] Shang W, Wang Z. The Update of NGAL in Acute Kidney Injury[J]. Curr Protein Pept Sci,2017,18(12):1211-1217.
[11] Wu J, Shao X, Lu K, et al. Urinary RBP and NGAL Levels are Associated with Nephropathy in Patients with Type2 Diabetes[J]. Cell Physiol Biochem,2017,42(2):594-602.
[12] Wu J, Ding Y, Zhu C, et al. Urinary TNF-αand NGAL are correlated with the progression of nephropathy in patients with type 2 diabetes[J]. Exp Ther Med,2013,6(6):1482-1488.
[13] Bolignano D, Lacquaniti A, Coppolino G, et al. Neutrophil gelatinase-associated lipocalin as an early biomarker of nephropathy in diabetic patients[J]. Kidney Blood Press Res,2009,32(2):91-98.
[14] Yang YH, He XJ, Chen SR, et al. Changes of serum and urine neutrophil gelatinase-associated lipocalin in type-2diabetic patients with nephropathy:one year observational follow-up study[J]. Endocrine,2009,36(1):45-51.
[15] Fu WJ, Xiong SL, Fang YG, et al. Urinary tubular biomarkers in short-term type 2 diabetes mellitus patients:a cross-sectional study[J]. Endocrine,2012,41(1):82-88.