Identification of Putative Kidney-Derived Proteins in Plasma using Nanoparticle Enrichment

Abstract Many diseases, including diabetes and hypertension, can lead to kidney damage, often resulting in long-term health complications and organ failure. Both animal and human studies have documented a causal relationship between high dietary sodium intake and elevated blood pressure. We explored a proteomics analysis of plasma samples to detect early kidney damage in response to a high sodium (HS) diet through the quantification of putative kidney-derived proteins in plasma for early disease detection. Plasma samples from 7 female baboons fed a high sodium diet for 6 weeks were collected before and after the HS diet challenge. Plasma samples were analyzed using a novel nanoparticle enrichment protocol. Using Seer’s Proteograph XT workflow, we identified 2,294 plasma proteins across all samples. Of these, 2,139 proteins were annotated with gene IDs, including 453 proteins previously identified in kidney lysate. 1,969 of these proteins are annotated in the Human Protein Atlas as expressed in the kidney, and 37 are classified as elevated. 97 proteins were only detected in plasma samples collected after the 6 week HS diet. We also identified 35 nominally significant differentially abundant proteins (p0.05), with 84% of these detected at higher abundance after HS exposure. Additional proteins were identified in two animals that demonstrated an increase in blood pressure in response to the HS diet. Our analysis reports an increase in putative kidney-derived proteins in plasma after HS diet exposure, and demonstrates the suitability of the Seer’s Proteograph technology to identify potential biomarkers for kidney tissue damage.