Circulating Protein and Metabolite Correlates of Histologically Confirmed Diabetic Kidney Disease

作者：Carolina Lopez-Silva, Aditya Surapaneni, Insa M. Schmidt, D. Upadhyay, Anand Srivastava, Ragnar Pálsson, Isaac E. Stillman, Eugene P. Rhee, Sushrut S. Waikar, Morgan E. Grams · 发表于：Kidney Medicine · 年份：2024 · DOI：10.1016/j.xkme.2024.100920 · 被引用次数：6 · 研究领域：Chronic Kidney Disease and Diabetes、Metabolomics and Mass Spectrometry Studies、Dialysis and Renal Disease Management

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. Study Design A cross-sectional study. Setting & Participants A total of 434 Boston Kidney Biopsy Cohort participants. Predictors Histopathological diagnosis of DKD on biopsy. Outcomes Proteins and metabolites associated with DKD. Analytical Approach 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. Results 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 discrim...