我们的目标是确定亚洲早发 2 型糖尿病 (T2DM) 患者中七种主要候选蛋白质生物标志物与糖尿病肾病 (DKD) 进展的关联。824 名 T2DM 患者（发病年龄≤40 岁）根据每年估计肾小球滤过率 (eGFR) 较基线下降 >3ml/min/1.73m2 或 >40%。血浆富含亮氨酸的 α-2-糖蛋白 1 (pLRG1)、肿瘤坏死因子受体 1 (pTNF-R1)、色素上皮衍生因子 (pPEDF)、尿 α-1-微球蛋白 (uA1M)、肾损伤分子 1 (使用酶联免疫测定法测量 uKIM-1)、触珠蛋白 (uHP) 和尿调节素 (uUMOD)。在 5.7 年的随访中，25.2% 的患者为 DKD 进展者。 pLRG1、pTNF-R1、pPEDF、uA1M、uKIM-1 和 uHP 水平升高与 DKD 进展相关。调整临床协变量后，pTNF-R1 水平与 DKD 进展之间的关联仍然存在（OR 1.84，95% CI 1.44-2.34，p<0.001）。 pTNF-R1 的作用部分是通过高血糖 (8%) 和白蛋白尿 (10%) 介导的。将 pTNF-R1 纳入基于临床变量的模型将预测 DKD 进展的受试者工作特征曲线下面积提高了 0.02，从 0.72 (95% CI 0.68-0.76) 提高到 0.74 (95% CI 0.70-0.78)，p =0.099。在七种主要候选蛋白中，pTNF-R1 部分通过高血糖和白蛋白尿介导，有力地预测了患有年轻发病 T2DM 的亚洲人的 DKD 进展。版权所有 © 2024。由 Elsevier B.V. 出版。

We aim to determine the association of seven major candidate protein biomarkers and diabetic kidney disease (DKD) progression among Asians with young-onset type 2 diabetes mellitus (T2DM).824 T2DM patients (onset ≤ 40 years old) were classified as DKD progressors based on yearly estimated glomerular filtration rate (eGFR) decline of >3 ml/min/1.73 m2 or >40 % from baseline. Plasma leucine-rich α-2-glycoprotein 1 (pLRG1), tumor necrosis factor-receptor 1 (pTNF-R1), pigment epithelium-derived factor (pPEDF), urinary α-1-microglobulin (uA1M), kidney injury molecular 1 (uKIM-1), haptoglobin (uHP) and uromodulin (uUMOD) were measured using enzyme-linked immunoassays.Over 5.7 years of follow-up, 25.2 % of patients were DKD progressors. Elevated levels of pLRG1, pTNF-R1, pPEDF, uA1M, uKIM-1 and uHP were associated with DKD progression. The association between pTNF-R1 levels and DKD progression persisted after adjusting for clinical covariates (OR 1.84, 95 %CI 1.44-2.34, p < 0.001). The effects of pTNF-R1 were partially mediated through hyperglycemia (8 %) and albuminuria (10 %). Inclusion of pTNF-R1 in a clinical variable-based model improved the area under the receiver operating characteristics curve for predicting DKD progression by 0.02, from 0.72 (95 %CI 0.68-0.76) to 0.74 (95 %CI 0.70-0.78), p = 0.099.Among seven major candidate proteins, pTNF-R1 partially mediated through hyperglycemia and albuminuria, robustly predicted DKD progression among Asians with young-onset T2DM.Copyright © 2024. Published by Elsevier B.V.