Lopez-Silva Carolina, Surapaneni Aditya, Schmidt Insa M, Upadhyay Dhairya, Srivastava Anand, Palsson Ragnar, Stillman Isaac E, Rhee Eugene P, Waikar Sushrut S, Grams Morgan E
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Division of Precision Medicine, NYU Grossman School of Medicine, New York City, NY.
Kidney Med. 2024 Oct 16;6(12):100920. doi: 10.1016/j.xkme.2024.100920. eCollection 2024 Dec.
RATIONALE & OBJECTIVE: Diabetic kidney disease (DKD) is one of the leading causes of end-stage kidney disease globally. We aim to identify proteomic and metabolomic correlates of histologically confirmed DKD that may improve our understanding of its pathophysiology.
A cross-sectional study.
SETTING & PARTICIPANTS: A total of 434 Boston Kidney Biopsy Cohort participants.
Histopathological diagnosis of DKD on biopsy.
Proteins and metabolites associated with DKD.
We performed linear regression to identify circulating proteins and metabolites associated with a histopathological diagnosis of DKD (n = 81) compared with normal or thin basement membrane (n = 27), and other kidney diseases without diabetes (n = 279). Pathway enrichment analysis was used to explore biological pathways enriched in DKD. Identified proteins were assessed for their discriminative ability in cases of DKD versus a distinct set of 48 patients with diabetes but other kidney diseases.
After adjusting for age, sex, estimated glomerular filtration, and albuminuria levels, there were 8 proteins and 1 metabolite that differed between DKD and normal/thin basement membrane, and 84 proteins and 11 metabolites that differed between DKD and other kidney diseases without diabetes. Five proteins were significant in both comparisons: C-type mannose receptor 2, plexin-A1, plexin-D1, renin, and transmembrane glycoprotein NMB. The addition of these proteins improved discrimination over clinical variables alone of a histopathological diagnosis of DKD on biopsy among patients with diabetes (change in area under the curve 0.126; = 0.008).
A cross-sectional approach and lack of an external validation cohort.
Distinct proteins and biological pathways are correlated with a histopathological diagnosis of DKD.
糖尿病肾病（DKD）是全球终末期肾病的主要病因之一。我们旨在确定经组织学证实的DKD的蛋白质组学和代谢组学关联因素，以增进我们对其病理生理学的理解。
一项横断面研究。
共有434名波士顿肾活检队列参与者。
活检时DKD的组织病理学诊断。
与DKD相关的蛋白质和代谢物。
我们进行线性回归，以确定与DKD组织病理学诊断相关的循环蛋白和代谢物（n = 81），并与正常或薄基底膜（n = 27）以及无糖尿病的其他肾脏疾病（n = 279）进行比较。通路富集分析用于探索DKD中富集的生物学通路。评估所鉴定蛋白质在DKD与另一组48例患有糖尿病但患有其他肾脏疾病的患者之间的鉴别能力。
在调整年龄、性别、估计的肾小球滤过率和蛋白尿水平后，DKD与正常/薄基底膜之间有8种蛋白质和1种代谢物存在差异，DKD与无糖尿病的其他肾脏疾病之间有84种蛋白质和11种代谢物存在差异。在两项比较中，有5种蛋白质具有显著性：C型甘露糖受体2、丛蛋白A1、丛蛋白D1、肾素和跨膜糖蛋白NMB。添加这些蛋白质后，与仅使用临床变量相比，对糖尿病患者活检时DKD组织病理学诊断的鉴别能力有所提高（曲线下面积变化0.126；P = 0.008）。
横断面研究方法且缺乏外部验证队列。
不同的蛋白质和生物学通路与DKD的组织病理学诊断相关。
