Detection of diabetic nephropathy from advanced glycation endproducts (AGEs) differs in plasma and urine, and is dependent on the method of preparation
Detection of diabetic nephropathy from advanced glycation endproducts (AGEs) differs in plasma and urine, and is dependent on the method of preparation
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DOI：
10.1007/s00726-013-1533-x
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发表时间：
2014-02-01
期刊：
影响因子：
3.5
通讯作者：
Mauer, Michael
中科院分区：
文献类型：
--
作者：
Beisswenger, Paul J.;Howell, Scott K.;Mauer, Michael
晚期糖基化终产物（AGEs）和氧化产物（OP）的增加被认为是糖尿病肾病（DN）的致病因素。我们在糖尿病肾病自然史研究的103名年轻、正常白蛋白尿、血压正常的1型糖尿病患者中，研究了不同血浆和尿液标本中AGEs和OP与DN进展的关系。主要终点是电子显微镜测量的肾小球基底膜（GBM）宽度从基线到5年的变化;系膜体积分数的变化是次要终点。快速进展者（FP）定义为GBM增厚率的上四分位数（n = 24）;缓慢进展者（SP）为其余（n = 79）。采用液相色谱-三重四极杆质谱法测定了4种AGEs [3-脱氧葡萄糖醛酮和甲基乙二醛氢咪唑酮（DG 3 H1，MGH 1）和羧甲基赖氨酸和乙基赖氨酸（CML，CEL）]以及2种氧化产物蛋氨酸亚砜和氨基己二酸。在第5年对10 K血浆肌酐和血浆蛋白水解酶（PPD）进行测量，并在5年内的4个时间点对尿10 K肌酐进行测量。FP患者的尿滤液CEL水平显著较高，但在调整HbA 1c、性别和糖尿病持续时间后并不如此。FP组MGHI、CEL和CML血浆滤液水平显著高于SP组（p < 0.05）。在PPD中，仅MGHI显示FP相对于SP的临界水平显著更高（p = 0.067），而其他产品均未显示相关性。AGE和OP测量与系膜扩张无关。在血浆糖化血红蛋白中，第5年时HbA 1c占GBM宽度变异的4.7%。当将MGHI、CEL和CML添加到模型中时，GBM宽度的变化比例增加至11.6%（增加6.9%）。
Increased advanced glycation endproducts (AGEs) and oxidation products (OPs) have been proposed as pathogenic for diabetic nephropathy (DN). We investigated the relationship between AGEs and OPs measured in different plasma and urine preparations, and progression of DN in 103 young, normoalbuminuric, normotensive participants with type 1 diabetes in the Natural History of Diabetic Nephropathy Study. The primary endpoint was electron microscopy-measured change in glomerular basement membrane (GBM) width from baseline to 5 years; change in mesangial fractional volume was a secondary endpoint. Fast progressors (FP) were defined as the upper quartile (n = 24) of rate of GBM thickening; slow progressors (SP) were the remainder (n = 79). Four AGEs [3-deoxyglucosone and methylglyoxal hydroimidazolones (DG3H1, MGH1) and carboxymethyl and ethyl lysine (CML, CEL)], and two oxidation products methionine sulfoxide and aminoadipic acid were measured by liquid chromatography, triple quadrupole mass spectrometry. Measurements were done on 10 K plasma filtrates and plasma proteolytic digests (PPD) at year 5, and at four time points over 5 years for urinary 10 K filtrates. Urinary filtrate CEL levels were significantly higher in FP, but not after adjustment for HbA1c, sex, and duration of diabetes. MGHI, CEL, and CML plasma filtrate levels were significantly higher in FP relative to SP (p < 0.05). In PPD, only MGHI showed borderline significantly higher levels in FP relative to SP (p = 0.067), while no other product showed correlation. AGE and OP measurements were not correlated with mesangial expansion. In plasma filtrates, HbA1c at year 5 accounted for 4.7 % of the variation in GBM width. The proportion of variation in GBM width was increased to 11.6 % when MGHI, CEL, and CML were added to the model (6.9 % increase).