Related Experiment Video
Updated: Jun 5, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Circulating Protein and Metabolite Correlates of Histologically Confirmed Diabetic Kidney Disease
Carolina Lopez-Silva1, Aditya Surapaneni2, Insa M Schmidt3
1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
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; P = 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.
Related Concept Videos
01:20Renal Corpuscle
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
01:15Diabetes: Symptoms, Diagnosis, and Complications
01:10Nephrons
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
01:21External Anatomy of the Kidney
The kidneys are located in the retroperitoneal space on either side of the vertebral column, protected posteriorly by the 11th and 12th ribs. The right kidney sits slightly lower than the left owing to the presence of the liver...