National Health Commission (NHC) Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
Department of Endocrinology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
Front Endocrinol (Lausanne). 2024 Aug 20;15:1443573. doi: 10.3389/fendo.2024.1443573. eCollection 2024.
Several urinary biomarkers have good diagnostic value for diabetic kidney disease (DKD); however, the predictive value is limited with the use of single biomarkers. We investigated the clinical value of Luminex liquid suspension chip detection of several urinary biomarkers simultaneously.
The study included 737 patients: 585 with diabetes mellitus (DM) and 152 with DKD. Propensity score matching (PSM) of demographic and medical characteristics identified a subset of 78 patients (DM = 39, DKD = 39). Two Luminex liquid suspension chips were used to detect 11 urinary biomarkers according to their molecular weight and concentration. The biomarkers, including cystatin C (CysC), nephrin, epidermal growth factor (EGF), kidney injury molecule-1 (KIM-1), retinol-binding protein4 (RBP4), α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), vitamin D binding protein (VDBP), tissue inhibitor of metalloproteinases-1 (TIMP-1), tumor necrosis factor receptor-1 (TNFR-1), and tumor necrosis factor receptor-2 (TNFR-2) were compared in the DM and DKD groups. The diagnostic values of single biomarkers and various biomarker combinations for early diagnosis of DKD were assessed using receiver operating characteristic (ROC) curve analysis.
Urinary levels of VDBP, RBP4, and KIM-1 were markedly higher in the DKD group than in the DM group ( < 0.05), whereas the TIMP-1, TNFR-1, TNFR-2, α1-MG, β2-MG, CysC, nephrin, and EGF levels were not significantly different between the groups. RBP4, KIM-1, TNFR-2, and VDBP reached < 0.01 in univariate analysis and were entered into the final analysis. VDBP had the highest AUC (0.780, < 0.01), followed by RBP4 (0.711, < 0.01), KIM-1 (0.640, = 0.044), and TNFR-2 (0.615, = 0.081). However, a combination of these four urinary biomarkers had the highest AUC (0.812), with a sensitivity of 0.742 and a specificity of 0.760.
The urinary levels of VDBP, RBP4, KIM-1, and TNFR-2 can be detected simultaneously using Luminex liquid suspension chip technology. The combination of these biomarkers, which reflect different mechanisms of kidney damage, had the highest diagnostic value for DKD. However, this finding should be explored further to understand the synergistic effects of these biomarkers.
几种尿生物标志物对糖尿病肾病（DKD）具有良好的诊断价值；然而，使用单一生物标志物的预测价值有限。我们研究了同时使用Luminex 液相悬浮芯片检测几种尿生物标志物的临床价值。
这项研究包括 737 名患者：585 名患有糖尿病（DM），152 名患有 DKD。采用倾向评分匹配（PSM）对人口统计学和医学特征进行匹配，确定了 78 名患者亚组（DM=39 名，DKD=39 名）。根据分子质量和浓度，使用两种 Luminex 液相悬浮芯片检测 11 种尿生物标志物。生物标志物包括胱抑素 C（CysC）、足细胞蛋白（nephrin）、表皮生长因子（EGF）、肾损伤分子 1（KIM-1）、视黄醇结合蛋白 4（RBP4）、α1-微球蛋白（α1-MG）、β2-微球蛋白（β2-MG）、维生素 D 结合蛋白（VDBP）、金属蛋白酶组织抑制剂 1（TIMP-1）、肿瘤坏死因子受体 1（TNFR-1）和肿瘤坏死因子受体 2（TNFR-2）。使用受试者工作特征（ROC）曲线分析比较 DM 和 DKD 组中各生物标志物的诊断价值。
DKD 组尿液 VDBP、RBP4 和 KIM-1 水平明显高于 DM 组（ < 0.05），而 TIMP-1、TNFR-1、TNFR-2、α1-MG、β2-MG、CysC、nephrin 和 EGF 水平在两组间无显著差异。RBP4、KIM-1、TNFR-2 和 VDBP 在单因素分析中均 < 0.01，进入最终分析。VDBP 的 AUC 值最高（0.780， < 0.01），其次是 RBP4（0.711， < 0.01）、KIM-1（0.640，=0.044）和 TNFR-2（0.615，=0.081）。然而，这四种尿生物标志物的组合具有最高的 AUC（0.812），其灵敏度为 0.742，特异性为 0.760。
可以使用 Luminex 液相悬浮芯片技术同时检测 VDBP、RBP4、KIM-1 和 TNFR-2 的尿液水平。这些反映不同肾脏损伤机制的生物标志物的组合对 DKD 具有最高的诊断价值。然而，需要进一步探讨这一发现，以了解这些生物标志物的协同作用。
