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骨膜蛋白作为2型糖尿病肾损伤的组织和尿液生物标志物。

Periostin as a tissue and urinary biomarker of renal injury in type 2 diabetes mellitus.

作者信息

Satirapoj Bancha, Tassanasorn Surat, Charoenpitakchai Mongkon, Supasyndh Ouppatham

机构信息

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Department of Pathology, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

出版信息

PLoS One. 2015 Apr 17;10(4):e0124055. doi: 10.1371/journal.pone.0124055. eCollection 2015.

Abstract

BACKGROUND

Improving the early detection of diabetic nephropathy remains a great challenge in disease management. Periostin is a marker of renal tubular injury and related to progressive kidney injury in animal models of chronic kidney disease. The clinical implications of urinary periostin activities in patients with type 2 diabetes have not been evaluated.

METHODS

Urine samples were obtained from 30 healthy volunteers and 328 type 2 diabetic patients with normoalbuminuria (n=114), microalbuminuria (n=100) and macroalbuminuria (n=114). The excretion levels of urinary periostin were quantified with enzyme-linked immunosorbent assay. Immunohistochemical periostin expression was determined in kidney tissues from overt diabetic nephropathy.

RESULTS

Increased periostin expression in glomeruli and tubular epithelium in diabetic renal pathology was observed. Urinary periostin levels were significantly elevated in the patients of the normoalbuminuria [3.06 (IQR: 1.12, 6.77) ng/mgCr], microalbuminuria [8.71 (IQR: 5.09, 19.29) ng/mgCr] and macroalbuminuria [13.58 (IQR: 3.99, 16.19) ng/mgCr] compared with healthy controls [1.15 (IQR: 0.60, 1.63) ng/mgCr] (P<0.01).Increased urine periostin level significantly correlated with aging, high albuminuria and decline of GFR. Urine periostin ELISA also demonstrated high performance for the diagnosis of established normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes (AUC 0.78 (95%CI, 0.71 to 0.86), 0.99 (95%CI, 0.98 to 1.00) and 0.95 (95%CI, 0.91 to 0.98), respectively).

CONCLUSION

The study indicates that increased urine periostin levels can be detected in patients with type 2 diabetes before the onset of significant albuminuria. Urinary periostin is an associated renal derangement in patients with established diabetic nephropathy and it may be used as an early marker of diabetic renal injury.

摘要

背景

改善糖尿病肾病的早期检测仍是疾病管理中的一项重大挑战。骨膜蛋白是肾小管损伤的标志物,与慢性肾脏病动物模型中的进行性肾损伤有关。2型糖尿病患者尿骨膜蛋白活性的临床意义尚未得到评估。

方法

收集30名健康志愿者和328名2型糖尿病患者的尿液样本,这些患者分别为正常白蛋白尿(n = 114)、微量白蛋白尿(n = 100)和大量白蛋白尿(n = 114)。采用酶联免疫吸附测定法定量尿骨膜蛋白的排泄水平。在显性糖尿病肾病患者的肾组织中测定骨膜蛋白的免疫组化表达。

结果

在糖尿病肾脏病理中观察到肾小球和肾小管上皮细胞中骨膜蛋白表达增加。与健康对照[1.15(四分位间距:0.60,1.63)ng/mgCr]相比,正常白蛋白尿患者[3.06(四分位间距:1.12,6.77)ng/mgCr]、微量白蛋白尿患者[8.71(四分位间距:5.09,19.29)ng/mgCr]和大量白蛋白尿患者[13.58(四分位间距:3.99,16.19)ng/mgCr]的尿骨膜蛋白水平显著升高(P<0.01)。尿骨膜蛋白水平升高与年龄增长、高白蛋白尿和肾小球滤过率下降显著相关。尿骨膜蛋白酶联免疫吸附测定法对已确诊的正常白蛋白尿、微量白蛋白尿和大量白蛋白尿2型糖尿病的诊断也具有较高的效能(曲线下面积分别为0.78(95%可信区间,0.71至0.86)、0.99(95%可信区间,0.98至1.00)和0.95(95%可信区间,0.91至0.98))。

结论

该研究表明,在2型糖尿病患者出现明显白蛋白尿之前即可检测到尿骨膜蛋白水平升高。尿骨膜蛋白是已确诊糖尿病肾病患者肾脏紊乱的相关指标,可作为糖尿病肾损伤的早期标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f9/4401767/fdc94f69b9f2/pone.0124055.g001.jpg

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