Rossing Kasper, Mischak Harald, Dakna Mohammed, Zürbig Petra, Novak Jan, Julian Bruce A, Good David M, Coon Joshua J, Tarnow Lise, Rossing Peter
Steno Diabetes Center, Niels Steensens Vej 2, DK 2820 Gentofte, Denmark.
J Am Soc Nephrol. 2008 Jul;19(7):1283-90. doi: 10.1681/ASN.2007091025. Epub 2008 Apr 30.
Urinary biomarkers for diabetes, diabetic nephropathy, and nondiabetic proteinuric renal diseases were sought. For 305 individuals, biomarkers were defined and validated in blinded data sets using high-resolution capillary electrophoresis coupled with electrospray-ionization mass spectrometry. A panel of 40 biomarkers distinguished patients with diabetes from healthy individuals with 89% sensitivity and 91% specificity. Among patients with diabetes, 102 urinary biomarkers differed significantly between patients with normoalbuminuria and nephropathy, and a model that included 65 of these correctly identified diabetic nephropathy with 97% sensitivity and specificity. Furthermore, this panel of biomarkers identified patients who had microalbuminuria and diabetes and progressed toward overt diabetic nephropathy over 3 yr. Differentiation between diabetic nephropathy and other chronic renal diseases reached 81% sensitivity and 91% specificity. Many of the biomarkers were fragments of collagen type I, and quantities were reduced in patients with diabetes or diabetic nephropathy. In conclusion, this study shows that analysis of the urinary proteome may allow early detection of diabetic nephropathy and may provide prognostic information.
人们一直在寻找用于诊断糖尿病、糖尿病肾病和非糖尿病性蛋白尿性肾脏疾病的尿液生物标志物。对于305名个体,使用高分辨率毛细管电泳结合电喷雾电离质谱法在盲法数据集中定义并验证了生物标志物。一组40种生物标志物可将糖尿病患者与健康个体区分开来,灵敏度为89%,特异性为91%。在糖尿病患者中,102种尿液生物标志物在正常白蛋白尿患者和肾病患者之间存在显著差异,一个包含其中65种生物标志物的模型能够以97%的灵敏度和特异性正确识别糖尿病肾病。此外,这组生物标志物还能识别出患有微量白蛋白尿和糖尿病且在3年内发展为显性糖尿病肾病的患者。糖尿病肾病与其他慢性肾脏疾病之间的鉴别灵敏度达到81%,特异性达到91%。许多生物标志物是I型胶原蛋白的片段,糖尿病或糖尿病肾病患者体内这些片段的数量会减少。总之,这项研究表明,对尿液蛋白质组的分析可能有助于早期发现糖尿病肾病,并可能提供预后信息。