糖化肽与2型糖尿病近端肾小管功能障碍有关。
Glycated peptides are associated with proximal tubule dysfunction in type 2 diabetes mellitus.
作者信息
Petrica Ligia, Vlad Adrian, Gluhovschi Gheorghe, Zamfir Alina, Popescu Cristina, Gadalean Florica, Dumitrascu Victor, Vlad Daliborca, Popescu Roxana, Velciov Silvia, Gluhovschi Cristina, Bob Flaviu, Milas Oana, Ursoniu Sorin
机构信息
Department of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Department of Diabetes and Metabolic Diseases, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
出版信息
Int J Clin Exp Med. 2015 Feb 15;8(2):2516-25. eCollection 2015.
BACKGROUND
Advanced glycation end-products have been involved in the pathogenesis of proximal tubule dysfunction which characterizes diabetic tubulopathy.
METHODS
A total of 76 Type 2 diabetes mellitus patients and 28 healthy controls were evaluated concerning a potential association of glycated peptides with proximal tubule dysfunction by assessing urine albumin:creatinine ratio, urinary alpha1-microglobulin, urinary neutrophil gelatinase-associated lipocalin, plasma and urinary advanced glycation end-products, plasma asymmetric dimethyl-arginine, serum cystatin C. Fully automated chip-nanoelectrospray ionization and high-capacity ion trap multistage mass spectrometry characterized the urinary proteomic profile.
RESULTS
The urinary glycated proteins displayed a molecular weight of 15,121.4 Da in normoalbuminuric patients and of 30,180.4 Da in microalbuminuric patients. Urinary alpha1-microglobulin and neutrophil gelatinase-associated lipocalin correlated with urinary advanced glycation end-products (R(2)=0.586; R(2)=0.415), urine albumin: creatinine ratio (R(2)=0.292; R(2)=0.116), estimated glomerular filtration rate (R(2)=0.172; R(2)=0.135), serum cystatin C (R(2)=0.146; R(2)=0.129), but not with asymmetric dimethyl-arginine. In multivariable regression analysis models, the correlations for urinary alpha1-microglobulin and neutrophil gelatinase-associated lipocalin remained significant with urine albumin: creatinine ratio, urinary advanced glycation end-products, estimated glomerular filtration rate (P<0.0001, R(2)=0.674; P<0.0001, R(2)=0.551; P<0.0001, R(2)=0.482).
CONCLUSIONS
In patients with Type 2 diabetes mellitus urinary glycated peptides are associated with proximal tubule dysfunction. The proteomic patterns of urinary glycated peptides could differentiate normo- from microalbuminuric patients and may explain a potential relation between the size and the glycation status of glycated peptides, and the extent of proximal tubule dysfunction. The lack of correlation between parameters of endothelial dysfunction and proximal tubule dysfunction cannot exclude glomerular involvement in early diabetic nephropathy.
背景
晚期糖基化终产物参与了近端肾小管功能障碍的发病机制，近端肾小管功能障碍是糖尿病肾小管病变的特征。
方法
通过评估尿白蛋白：肌酐比值、尿α1-微球蛋白、尿中性粒细胞明胶酶相关脂质运载蛋白、血浆和尿晚期糖基化终产物、血浆不对称二甲基精氨酸、血清胱抑素C，对76例2型糖尿病患者和28例健康对照者进行评估，以探讨糖化肽与近端肾小管功能障碍之间的潜在关联。采用全自动芯片-纳电喷雾电离和高容量离子阱多级质谱对尿蛋白质组学图谱进行表征。
结果
正常白蛋白尿患者尿糖化蛋白的分子量为15,121.4 Da，微量白蛋白尿患者为30,180.4 Da。尿α1-微球蛋白和中性粒细胞明胶酶相关脂质运载蛋白与尿晚期糖基化终产物（R²=0.586；R²=0.415）、尿白蛋白：肌酐比值（R²=0.292；R²=0.116）、估计肾小球滤过率（R²=0.172；R²=0.135）、血清胱抑素C（R²=0.146；R²=0.129）相关，但与不对称二甲基精氨酸无关。在多变量回归分析模型中，尿α1-微球蛋白和中性粒细胞明胶酶相关脂质运载蛋白与尿白蛋白：肌酐比值、尿晚期糖基化终产物、估计肾小球滤过率的相关性仍然显著（P<0.0001，R²=0.674；P<0.0001，R²=0.551；P<0.0001，R²=0.482）。
结论
在2型糖尿病患者中，尿糖化肽与近端肾小管功能障碍相关。尿糖化肽的蛋白质组学模式可区分正常白蛋白尿和微量白蛋白尿患者，并可能解释糖化肽的大小与糖化状态以及近端肾小管功能障碍程度之间的潜在关系。内皮功能障碍参数与近端肾小管功能障碍之间缺乏相关性不能排除肾小球参与早期糖尿病肾病。
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