A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus
A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus
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DOI：
10.1007/s00125-011-2339-6
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发表时间：
2012-02-01
期刊：
影响因子：
8.2
通讯作者：
Ong, C. N.
中科院分区：
文献类型：
--
作者：
Ng, D. P. K.;Salim, A.;Ong, C. N.
我们进行了一项尿代谢组学研究，以了解非蛋白尿2型糖尿病患者的低估计GFR（eGFR）。eGFR低的病例（n = 44）和对照组（n = 46）的eGFR值分别< 60和千分之一日元60 ml min（-1）1.73 m（-2），这是使用肾脏疾病饮食改良公式计算的。通过液相色谱/质谱法（LC/MS）和GC/MS分析尿样。错误发现率用于调整多个假设检验，并使用最小绝对收缩和选择算子逻辑回归来选择最能预测低eGFR状态的代谢物。在校正多个假设检验后，11种GC/MS代谢物与低eGFR密切相关（最小调整p值= 2.62 x 10（-14），最大调整p值= 3.84 x 10（-2））。在回归分析中，辛醇、草酸、磷酸、苯甲酰胺、肌酐、3，5-二甲氧基扁桃酰胺和N-乙酰谷氨酰胺被选为预测的最佳子集，并允许对低eGFR进行极好的分类（AUC = 0.996）。在LC/MS中，在考虑多重假设检验后，19种代谢物仍具有显著性（最小调整p值= 2.04 x 10（-4），最大调整p值= 4.48 x 10（-2）），几种代谢物显示出与尿毒症毒素硫酸吲哚酚相关性更强的证据（调整p值= 3.03 x 10（-2））。排除了混杂因素对代谢物之间相关性的潜在影响。我们的研究对低eGFR产生了实质性的新见解，并为其检测提供了一系列潜在的尿液生物标志物。
We carried out a urinary metabolomic study to gain insight into low estimated GFR (eGFR) in patients with non-proteinuric type 2 diabetes.Patients were identified as being non-proteinuric using multiple urinalyses. Cases (n = 44) with low eGFR and controls (n = 46) had eGFR values < 60 and a parts per thousand yen60 ml min(-1) 1.73 m(-2), respectively, as calculated using the Modification of Diet in Renal Disease formula. Urine samples were analysed by liquid chromatography/mass spectrometry (LC/MS) and GC/MS. False discovery rates were used to adjust for multiple hypotheses testing, and selection of metabolites that best predicted low eGFR status was achieved using least absolute shrinkage and selection operator logistic regression.Eleven GC/MS metabolites were strongly associated with low eGFR after correction for multiple hypotheses testing (smallest adjusted p value = 2.62 x 10(-14), largest adjusted p value = 3.84 x 10(-2)). In regression analysis, octanol, oxalic acid, phosphoric acid, benzamide, creatinine, 3,5-dimethoxymandelic amide and N-acetylglutamine were selected as the best subset for prediction and allowed excellent classification of low eGFR (AUC = 0.996). In LC/MS, 19 metabolites remained significant after multiple hypotheses testing had been taken into account (smallest adjusted p value = 2.04 x 10(-4), largest adjusted p value = 4.48 x 10(-2)), and several metabolites showed stronger evidence of association relative to the uraemic toxin, indoxyl sulphate (adjusted p value = 3.03 x 10(-2)). The potential effect of confounding on the association between metabolites was excluded.Our study has yielded substantial new insight into low eGFR and provided a collection of potential urinary biomarkers for its detection.