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Circulating Protein and Metabolite Correlates of Histologically Confirmed Diabetic Kidney Disease. | LitMetric
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 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).Limitations : A cross-sectional approach and lack of an external validation cohort.Conclusions : Distinct proteins and biological pathways are correlated with a histopathological diagnosis of DKD.
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