Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China; Institute of Endocrinology and Metabolism, Shandong University, Jinan, China; Key Laboratory of Endocrinology and Metabolism, Shandong Province in Medicine and Health, Jinan, China; Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China; Institute of Endocrinology and Metabolism, Shandong University, Jinan, China; Key Laboratory of Endocrinology and Metabolism, Shandong Province in Medicine and Health, Jinan, China.
Arch Med Res. 2019 Jul;50(5):249-256. doi: 10.1016/j.arcmed.2019.08.007. Epub 2019 Oct 5.
Urokinase-type plasminogen activator receptor (uPAR) and its soluble form (suPAR) are new injury biomarkers that have been recently suggested to play a vital role in renal diseases.
We evaluated the expression of uPAR and the serum concentration of suPAR in type 2 diabetes (TDM) patients with diabetic kidney disease (DKD) to determine the role of this molecule as a biomarker in DKD. The uPAR immunohistochemical staining was performed in biopsy-confirmed DKD renal tissues. Meanwhile, the serum suPAR, Interleukin-18 (IL-18) and C-reactive protein (CRP) levels of 70 diabetic patients with or without DKD and 15 healthy controls were measured.
The uPAR expression in DKD patients was significantly increased compared to that in healthy controls and was widely colocalized with the podocyte marker WT1. Meanwhile, serum suPAR and IL-18 levels gradually increased as DKD progressed to the advanced stage. Moreover, serum suPAR and IL-18 levels were negatively correlated with eGFR (ρ = ‒0.734, ρ = ‒0.462, p <0.01) and positively correlated with the urine protein to creatinine ratio (UP/CR) (ρ = 0.730, ρ = 0.440, p <0.01). The suPAR AUC performed better than the IL-18 AUC for the diagnosis of proteinuria (0.845 vs. 0.753, p <0.01) and the decline of renal function (0.895 vs. 0.796, p <0.01).
The uPAR expressed in the renal tissues of DKD patients. The soluble form of uPAR, suPAR, can be detected in the serum of DKD patients and has a better diagnostic efficiency in the diagnosis of proteinuria and renal dysfunction in patients with TDM than that of IL-18.
尿激酶型纤溶酶原激活物受体（uPAR）及其可溶性形式（suPAR）是新的损伤生物标志物，最近有研究表明其在肾脏疾病中发挥着重要作用。
我们评估了 2 型糖尿病（T2DM）合并糖尿病肾病（DKD）患者中 uPAR 的表达和血清 suPAR 浓度，以确定该分子作为 DKD 生物标志物的作用。对活检证实的 DKD 肾组织进行 uPAR 免疫组织化学染色。同时，检测了 70 例伴有或不伴有 DKD 的糖尿病患者和 15 例健康对照者的血清 suPAR、白细胞介素-18（IL-18）和 C 反应蛋白（CRP）水平。
与健康对照组相比，DKD 患者的 uPAR 表达显著增加，且与足细胞标志物 WT1 广泛共定位。同时，随着 DKD 进展到晚期，血清 suPAR 和 IL-18 水平逐渐升高。此外，血清 suPAR 和 IL-18 水平与 eGFR 呈负相关（r = -0.734，r = -0.462，p <0.01），与尿蛋白/肌酐比值（UP/CR）呈正相关（r = 0.730，r = 0.440，p <0.01）。suPAR 的 AUC 对蛋白尿（0.845 比 0.753，p <0.01）和肾功能下降（0.895 比 0.796，p <0.01）的诊断效能优于 IL-18。
DKD 患者肾脏组织中表达 uPAR。DKD 患者血清中可检测到 uPAR 的可溶性形式 suPAR，其对 T2DM 患者蛋白尿和肾功能障碍的诊断效率优于 IL-18。
