Urinary Exosomal mRNA of WT1 as Diagnostic and Prognostic Biomarker for Diabetic Nephropathy
Urinary Exosomal mRNA of WT1 as Diagnostic and Prognostic Biomarker for Diabetic Nephropathy
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DOI：
10.2152/jmi.65.208
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发表时间：
2018-08-01
影响因子：
0.7
通讯作者：
Doi, Toshio
中科院分区：
文献类型：
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作者：
Abe, Hideharu;Sakurai, Akiko;Doi, Toshio
糖尿病肾病（DN）是终末期肾衰竭的主要原因，与其他肾脏疾病原因相比，其发病率和死亡率增加。蛋白尿通常是DN存在的第一个临床指标。然而，白蛋白尿或蛋白尿是各种肾脏疾病患者的常见症状。因此，需要用于诊断DN的特异性生物标志物。DN的主要标志是肾小球足细胞的进行性损伤和死亡，导致蛋白质泄漏到尿液中。足细胞释放的尿外泌体是含有起源细胞信息的微泡。足细胞衍生的信号转导因子（PDSTFs）是评估足细胞损伤的良好候选者。糖尿病肾病和微小病变型肾病患者尿外泌体中PDSTFs的表达谱不同。此外，外泌体中的PDSTF分子来源于高糖条件下的原代鼠足细胞。在尿外泌体中的PDSTF中，Wilms肿瘤1（WT 1）水平反映了患者中糖尿病肾小球的损伤。尿外泌体WT1可以预测eGFR在随后几年的下降。总之，尿外泌体WT1是改善DN患者危险分层的有用生物标志物。
Diabetic nephropathy (DN) is the major cause of end-stage renal failure and is associated with increased morbidity and mortality as compared to other causes of renal disease. Albuminuria is often the first clinical indicator of the presence of DN. However, albuminuria or proteinuria is a common symptom in patients with various renal disorders. Therefore, specific biomarkers for the diagnosis of DN are required. A primary hallmark of DN is the progressive damage and death of glomerular podocytes, resulting in the leaking of proteins into the urine. Urinary exosomes released by podocytes are microvesicles containing information of the originated cells. Podocyte-derived signal transduction factors (PDSTFs) are good candidates to assess podocyte injuries. The profile of PDSTFs in urinary exosomes from patients with DN is different from that from patients with minimal change nehrotic syndrome. In addition, PDSTFs molecules in exosomes were derived from primary murine podocytes under high glucose conditions. Among PDSTFs in urinary exosomes, Wilms tumor 1 (WT1) levels reflected damage of diabetic glomeruli in the patients. Urinary exosomal WT1 can predict the decline in eGFR for the following several years. In conclusion, urinary exosomal WT1 is a useful biomarker to improve risk stratification in patients with DN.