Alterations in the Circulating Proteome Associated with Albuminuria

Area of Science:

• Proteomics
• Nephrology
• Biomarker Discovery

Background:

• Albuminuria is a critical indicator in Chronic Kidney Disease (CKD) diagnosis, staging, and prognosis.
• While GFR decline is well-studied, the proteomic underpinnings of albuminuria remain less explored.
• Understanding circulating proteins associated with albuminuria can offer new insights into CKD pathogenesis.

Purpose of the Study:

• To investigate circulating proteins associated with higher levels of albuminuria in individuals with CKD.
• To identify novel protein targets and signaling pathways implicated in albuminuria.
• To validate proteomic findings across diverse CKD cohorts.

Main Methods:

• Employed a large-scale proteomic platform to analyze nearly 7000 circulating proteins.
• Conducted cross-sectional and longitudinal analyses in the African American Study of Kidney Disease and Hypertension (AASK) cohort.
• Replicated findings in independent cohorts: Atherosclerosis Risk in Communities (ARIC) study and Chronic Renal Insufficiency Cohort (CRIC).

Main Results:

• Identified 104 proteins significantly associated with albuminuria in the AASK cohort.
• Successfully replicated a substantial proportion of these associations in the ARIC and CRIC cohorts.
• Strongest associations were observed for LMAN2, TNFSFR1B, and members of the ephrin superfamily, with pathway analysis confirming ephrin family enrichment.

Conclusions:

• Large-scale proteomic analysis in CKD patients identified numerous proteins linked to albuminuria.
• The findings suggest a significant role for ephrin signaling in the progression of albuminuria.
• This research provides potential novel biomarkers and therapeutic targets for managing CKD.