Urinary DcR2 is a novel biomarker for tubulointerstitial injury in patients with diabetic nephropathy
Urinary DcR2 is a novel biomarker for tubulointerstitial injury in patients with diabetic nephropathy
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尿DcR2是糖尿病肾病患者肾小管间质损伤的新型生物标志物
DOI：
10.1152/ajprenal.00689.2016
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发表时间：
2017-08-01
影响因子：
4.2
通讯作者：
He, Ya-Ni
中科院分区：
文献类型：
--
作者：
Chen, Jia;Zhang, Wei-Wei;He, Ya-Ni
肾小管间质损伤（TII）在糖尿病肾病（DN）的进展中起着至关重要的作用，但在 DN 管理中缺乏监测 TII 的特异性和敏感生物标志物。本研究旨在探讨尿诱饵受体 2 (uDcR2) 是否可以作为评估 DN 中 TII 的新型非侵入性生物标志物。我们招募了 311 名 2 型糖尿病患者和 139 名经肾活检确诊的 DN 患者。采用ELISA法测定uDcR2水平，免疫组化法检测肾DcR2表达。评估了uDcR2和肾DcR2以及肾功能参数之间的关联。受试者工作特征 (ROC) 曲线分析了 uDcR2 的曲线下面积 (AUC)，用于评估 TII。用近端和远端肾小管标记物对肾 DCR2 进行双染色；衰老标记物 p16、p21 和衰老相关 β-半乳糖苷酶 (SA-β-gal)；以及纤维化标记物胶原蛋白 I 和 IV。我们发现DcR2主要在肾近曲小管中表达； uDcR2 水平按蛋白尿层升高，与糖尿病患者的肾功能参数相关，并与 DN 中肾小管 DcR2 的百分比和 TII 评分相关。 uDcR2 通过 ROC 分析评估 DN 中 TII 的 AUC 为 0.909。几乎所有肾小管DcR2均与p16和p21共表达，并且近一半以上的肾小管DcR2呈SA-β-gal阳性，主要出现在DN的I型和IV型胶原蛋白阳性区域。我们的结果表明 uDcR2 有可能作为 TII 的新型生物标志物，并可能反映 DN 发病机制中肾近端肾小管细胞的衰老。
Tubulointerstitial injury (TII) plays a crucial role in the progression of diabetic nephropathy (DN), but lack of specific and sensitive biomarkers for monitoring TII in DN management. This study is to investigate whether urinary decoy receptor 2 (uDcR2) could serve as a novel noninvasive biomarker for assessing TII in DN. We recruited 311 type 2 diabetics and 139 DN patients who were diagnosed by renal biopsy. uDcR2 levels were measured by ELISA, and renal DcR2 expression was detected immunohistochemically. Associations between uDcR2 and renal DcR2 and renal functional parameters were evaluated. Receiver operating characteristics (ROC) curve analyzed area under the curve (AUC) of uDcR2 for assessing TII. Double staining was undertaken for renal DcR2 with proximal and distal tubular markers; senescent markers p16, p21, and senescence-associated beta-galactosidase (SA-beta-gal); and fibrotic markers collagen I and IV. We found DcR2 was primarily expressed in renal proximal tubules; uDcR2 levels were elevated per albuminuria stratum and correlated with renal functional parameters in diabetics and were associated with percentage of tubular DcR2 and TII score in DN. The uDcR2 had an AUC of 0.909 for assessing TII in DN by ROC analysis. Almost all tubular DcR2 was coexpressed with p16 and p21, and nearly more than one-half of tubular DcR2 was positive for SA-beta-gal, primarily in collagen I-and IV-positive regions of DN. Our results indicate uDcR2 could potentially serve as a novel biomarker for TII and may reflect senescence of renal proximal tubular cells in DN pathogenesis.