NGAL测定在糖尿病肾脏疾病中的价值及其与炎症因子的相关性
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摘要
目的观察血、尿中性粒细胞明胶酶相关载脂蛋白(NGAL)以及炎症细胞因子在2型糖尿病(T2DM)肾脏疾病(DKD)患者体内的变化,探讨NGAL是否是与微炎症有关的DKD早期诊断和监测病情的标志物。方法 T2DM患者93例,分为正常白蛋白尿(NA)组(n=31)、微量白蛋白尿(MA)组(n=31)和大量白蛋白(CA)组(n=31),另选取正常对照(NC)组(n=31)。ELISA法测定血、尿NGAL,血白介素(IL)-10、IL-6、肿瘤坏死因子(TNF-α)和尿单核细胞趋化蛋白-1(MCP-1)水平,分析血、尿NGAL与肾功能相关指标(尿蛋白、血肌酐)、炎症细胞因子、糖脂代谢之间的相关关系。结果 (1)与NC组比较,T2DM组血NGAL、IL-6、TNF-α和尿NGAL、MCP-1水平显著增高(P<0.05);血IL-10水平显著减低(P<0.05)。(2)与NC组比较,T2DM的NA组血、尿NGAL水平显著升高,差异有统计学意义(P<0.05)。(3)T2DM组间比较:三组间尿NGAL差异有统计学意义(P<0.05),随尿蛋白水平降低而逐渐递减;CA组的血NGAL显著高于MA组和NA组(P<0.05)。(4)逐步线性回归显示T2DM患者中尿白蛋白/肌酐(UACR)(t=445.034,P<0.001)、TNF-α(t=13.822,P<0.001)是尿NGAL影响因子,与尿NGAL呈正相关关系;糖化血红蛋白(t=3.266,P=0.002)、UACR(t=2.065,P=0.011)是血NGAL影响因子,与血NGAL呈正相关关系。结论 T2DM体内存在炎症细胞因子水平的变化。NGAL可能是T2DM慢性炎症和糖代谢紊乱中一个重要的连结点,血、尿NGAL是DKD敏感的早期诊断和监测病情的指标。
Objective To observe the changes of blood and urine NGAL and inflammatory cytokines in patients with type 2 diabetic kidney disease( DKD) and to explore whether NGAL is a marker of early diagnosis and monitoring of DKD associated with microinflammation. Methods Ninety-three patients with T2 DM had normal albuminuria( NA)( n = 31),microalbuminuria( MA)( n = 31) and a large number of albumin( CA) NC)( n = 31). Serum levels of NGAL,blood IL-10,IL-6,TNF-α and urinary MCP-1 were measured by ELISA. The correlation between blood and urine NGAL and renal function( urinary protein,serum creatinine),inflammatory cytokines and glucose and lipid metabolism were analyzed. Results(1) Compared with NC group,the levels of blood NGAL,IL-6,TNF-α and NGAL and MCP-1 in T2 DM group were significantly increased(P < 0. 05).(2) Compared with NC group,the level of NGAL in blood and urine of T2 DM NA group was significantly increased,the difference was statistically significant( P < 0. 05).(3) In comparison with T2 DM group: the difference of urinary NGAL among the three groups was statistically significant( P < 0. 05),and gradually decreased with the decrease of urinary protein level.The blood NGAL in CA group was significantly higher than that in MA group and NA group( P < 0. 05).(4) Stepwise linear regression showed that urinary albumin/creatinine( UACR)( t = 445. 034,P < 0. 001) and TNF-( t =13. 822,P < 0. 001) were the influencing factors of urine NGAL in patients with T2 DM,and positively correlated with urine NGAL. Glycosylated hemoglobin( t = 3. 266,P = 0. 002) and urine ACR( t = 2. 065,P = 0. 011) were the blood NGAL influencing factors,and positively correlated with blood NGAL. Conclusion There is a significant change in the level of inflammatory cytokines in T2 DM patients. NGAL may be an important link between chronic inflammation and glucose metabolism in T2 DM. Blood and urine NGAL is an indicator of DKD-sensitive early diagnosis and monitoring of the disease.
Objective To observe the changes of blood and urine NGAL and inflammatory cytokines in patients with type 2 diabetic kidney disease( DKD) and to explore whether NGAL is a marker of early diagnosis and monitoring of DKD associated with microinflammation. Methods Ninety-three patients with T2 DM had normal albuminuria( NA)( n = 31),microalbuminuria( MA)( n = 31) and a large number of albumin( CA) NC)( n = 31). Serum levels of NGAL,blood IL-10,IL-6,TNF-α and urinary MCP-1 were measured by ELISA. The correlation between blood and urine NGAL and renal function( urinary protein,serum creatinine),inflammatory cytokines and glucose and lipid metabolism were analyzed. Results(1) Compared with NC group,the levels of blood NGAL,IL-6,TNF-α and NGAL and MCP-1 in T2 DM group were significantly increased(P < 0. 05).(2) Compared with NC group,the level of NGAL in blood and urine of T2 DM NA group was significantly increased,the difference was statistically significant( P < 0. 05).(3) In comparison with T2 DM group: the difference of urinary NGAL among the three groups was statistically significant( P < 0. 05),and gradually decreased with the decrease of urinary protein level.The blood NGAL in CA group was significantly higher than that in MA group and NA group( P < 0. 05).(4) Stepwise linear regression showed that urinary albumin/creatinine( UACR)( t = 445. 034,P < 0. 001) and TNF-( t =13. 822,P < 0. 001) were the influencing factors of urine NGAL in patients with T2 DM,and positively correlated with urine NGAL. Glycosylated hemoglobin( t = 3. 266,P = 0. 002) and urine ACR( t = 2. 065,P = 0. 011) were the blood NGAL influencing factors,and positively correlated with blood NGAL. Conclusion There is a significant change in the level of inflammatory cytokines in T2 DM patients. NGAL may be an important link between chronic inflammation and glucose metabolism in T2 DM. Blood and urine NGAL is an indicator of DKD-sensitive early diagnosis and monitoring of the disease.
引文
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[6]Evangelia D,Anila D,Konstantinos L,et al.Improvements in the management of diabetic nephropathy[J].Rev Diabet Stud,2015,12(1-2):119-33.
[7]Lampropoulou I T,Stangou M,Papagianni A,et al.TNF-αand microalbuminuria in patients with type 2 diabetes mellitus[J].Diabetes Res,2014,2014:394206.
[8]Shoukry A,Bdeer Sel-A,El-Sokkary R H.Urinary monocyte chemoattractant protein-1 and vitamin D-binding protein as biomarkers for early detection of diabetic nephropathy in type 2 diabetes mellitus[J].Mol Cell Biochem,2015,408(1-2):25-35.
[9]Okada T,Nagao T,Matsumoto H,et al.Histological predictors for renal prognosis in diabetic nephropathy in diabetes mellitus type2 patients with overt proteinuria[J].Nephrology,2012,17(1):68-75.
[10]Yürük Y,ldrm Z,Nayr A,et al.Neutrophil gelatinase-associated lipocalin as an early sign of diabetic kidney injury in children[J].Clin Res Pediatr Endocrinol,2015,7(4):274-9.
[11]Moresco R N,Sangoi M B,De Carvalho J A,Diabetic nephropathy:traditional to proteomic markers[J].Clin Chim Acta,2013,421:17-30.
[12]Kim S S,Song S H,Kim I J,et al.Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients[J].Diabetes Res Clin Pract,2012,97(2):251-7.
[13]Shen S J,Hu Z X,Li Q H,et al.Implications of the changes in serum neutrophil gelatinase-associated lipocalin and cystatin C in patients with chronic kidney disease[J].Nephrology(Carlton),2014,19(3):129-35.
[14]6)Zyka A,Gala-Bdzińska A,Dumnicka P,et al.Is urinary NGAL determination useful for monitoring kidney function and assessment of cardiovascular disease?A 12-month observation of patients with type 2 diabetes[J].Dis Markers,2016:8489543.
[15]Patel M L,Sachan R,Misra R,et al.Prognostic significance of urinary NGAL in chronic kidney disease[J].Int J Nephrol Renovasc Dis,2015,8:139-44.
[16]Shvetsov M Y,Zheng A,Kozlovskaya L V.Urinary excretion of angiogenesis regulatory factors and renal injury markers in chronic glomerulonephritis:significance in the assessment of progression[J].Ter Arkh,2015,87(6):75-82.
[17]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):91-8.
[2]Cawood T J,Bashir M,Brady J et al.Urinary collagen IV andπGST:potential biomarkers for detecting localized kidney injury in diabetes-a pilot study[J].Am J Nephrol,2010,32(3):219-25.
[3]曾凡智,巧创淸,黄志红,等.硫酸庆大霉素诱导大鼠急性肾损伤模型血和尿NGAL、KIM-1的变化及意义[J].实用预防医学,2016,23(2):140-3.
[4]Nadkarni G N,Coca S G,Meisner A.Urinalysis findings and urinary kidney injury biomarker concentrations[J].BMC Nephrol,2017,618(1):218.
[5]Matsushita K,Woodward M,Bilo H J,et al.Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes:a meta-analysis[J].Lancet,2012,9854(380):1662-73.
[6]Evangelia D,Anila D,Konstantinos L,et al.Improvements in the management of diabetic nephropathy[J].Rev Diabet Stud,2015,12(1-2):119-33.
[7]Lampropoulou I T,Stangou M,Papagianni A,et al.TNF-αand microalbuminuria in patients with type 2 diabetes mellitus[J].Diabetes Res,2014,2014:394206.
[8]Shoukry A,Bdeer Sel-A,El-Sokkary R H.Urinary monocyte chemoattractant protein-1 and vitamin D-binding protein as biomarkers for early detection of diabetic nephropathy in type 2 diabetes mellitus[J].Mol Cell Biochem,2015,408(1-2):25-35.
[9]Okada T,Nagao T,Matsumoto H,et al.Histological predictors for renal prognosis in diabetic nephropathy in diabetes mellitus type2 patients with overt proteinuria[J].Nephrology,2012,17(1):68-75.
[10]Yürük Y,ldrm Z,Nayr A,et al.Neutrophil gelatinase-associated lipocalin as an early sign of diabetic kidney injury in children[J].Clin Res Pediatr Endocrinol,2015,7(4):274-9.
[11]Moresco R N,Sangoi M B,De Carvalho J A,Diabetic nephropathy:traditional to proteomic markers[J].Clin Chim Acta,2013,421:17-30.
[12]Kim S S,Song S H,Kim I J,et al.Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients[J].Diabetes Res Clin Pract,2012,97(2):251-7.
[13]Shen S J,Hu Z X,Li Q H,et al.Implications of the changes in serum neutrophil gelatinase-associated lipocalin and cystatin C in patients with chronic kidney disease[J].Nephrology(Carlton),2014,19(3):129-35.
[14]6)Zyka A,Gala-Bdzińska A,Dumnicka P,et al.Is urinary NGAL determination useful for monitoring kidney function and assessment of cardiovascular disease?A 12-month observation of patients with type 2 diabetes[J].Dis Markers,2016:8489543.
[15]Patel M L,Sachan R,Misra R,et al.Prognostic significance of urinary NGAL in chronic kidney disease[J].Int J Nephrol Renovasc Dis,2015,8:139-44.
[16]Shvetsov M Y,Zheng A,Kozlovskaya L V.Urinary excretion of angiogenesis regulatory factors and renal injury markers in chronic glomerulonephritis:significance in the assessment of progression[J].Ter Arkh,2015,87(6):75-82.
[17]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):91-8.