Diabetes：尿蛋白质组学可用于早期诊断糖尿病肾病

糖尿病肾病（DN）是一种逐渐进展的肾脏疾病，由长期高血糖引起的糖尿病的重要并发症。在西方国家，糖尿病肾病是透析的最常见原因。早期发现糖尿病肾病或许能运用药物进行干预治疗，从而延迟或避免使用肾脏替代治疗。为此，德国研究者Zürbig P进行了一项关于运用尿蛋白质组学诊断糖尿病肾病的研究（Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy）。研究结论发表在Diabetes 2012年12月刊。Diabetes 影响因子为8.1。

该研究运用毛细血管耦合质谱仪(CE-MS)来分析尿中小分子量蛋白质组。共选用35例1型和2型糖尿病患者的尿标本进行研究，所有试验对象的尿标本以前均使用慢性肾功能不全的生物标记分类器作为诊断糖尿病肾病的标准。

研究发现，与把尿白蛋白作为诊断糖尿病肾病的标准相比较(AUC 0.67)，使用毛细血管耦合质谱仪(CE-MS)能在大量蛋白尿出现前5年就可检测出阳性结果(AUC 0.93)。统计分析后得出使用以前诊断慢性肾功能不全的生物标记分类器作为诊断糖尿病肾病的标准已经过时。白蛋白分泌增加之前，胶原蛋白片段已经开始减少。因此，胶原蛋白片段是发生大量蛋白尿3-5年前的主要标记物。

该研究得出：早期测定尿中特定的胶原蛋白片段可以非损伤性判断糖尿病肾病发生风险。

doi: 10.2337/db12-0348
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Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy

Petra Zürbig1⇓, George Jerums2, Peter Hovind3, Richard J. MacIsaac4, Harald Mischak1,5, Stine E. Nielsen3, Sianna Panagiotopoulos2, Frederik Persson3 and Peter Rossing3

Diabetic nephropathy (DN) is a progressive kidney disease, a well-known complication of long-standing diabetes. DN is the most frequent reason for dialysis in many Western countries. Early detection may enable development of specific drugs and early initiation of therapy, thereby postponing/preventing the need for renal replacement therapy. We evaluated urinary proteome analysis as a tool for prediction of DN. Capillary electrophoresis–coupled mass spectrometry was used to profile the low–molecular weight proteome in urine. We examined urine samples from a longitudinal cohort of type 1 and 2 diabetic patients (n = 35) using a previously generated chronic kidney disease (CKD) biomarker classifier to assess peptides of collected urines for signs of DN. The application of this classifier to samples of normoalbuminuric subjects up to 5 years prior to development of macroalbuminuria enabled early detection of subsequent progression to macroalbuminuria (area under the curve [AUC] 0.93) compared with urinary albumin routinely used to determine the diagnosis (AUC 0.67). Statistical analysis of each urinary CKD biomarker depicted its regulation with respect to diagnosis of DN over time. Collagen fragments were prominent biomarkers 3–5 years before onset of macroalbuminuria. Before albumin excretion starts to increase, there is a decrease in collagen fragments. Urinary proteomics enables noninvasive assessment of DN risk at an early stage via determination of specific collagen fragments.