MSACL 2026 Abstract

Assessing Urine as a Noninvasive Representation of the Plasma Proteome in Paired Samples

Katelyn Brusach, Brian Searle
Mayo Clinic, Rochester, MN

Katelyn Brusach, PhD (Presenter) The Mayo Clinic

Presenter Bio: Katelyn Brusach is a postdoctoral research fellow at the Mayo Clinic. Her research focuses on leveraging mass spectrometry-based proteomics to explore biofluids for pathophysiological insights, particularly in chronic metabolic and inflammation-driven diseases. She aims to identify protein signatures that can advance early diagnosis, personalized treatment, and noninvasive diagnostics in conditions such as chronic kidney, liver, and pancreatic diseases.

Relevant Financial Disclosures (within past 24 months, reported on Apr 22, 2026) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

INTRODUCTION:
Biofluid-based assays are critical in measuring patient status without requiring biopsy. While traditionally one marker or biofluid is targeted, the relationship between protein presence, absence, or relative quantification across biofluids may provide biological insight. Our previous research has demonstrated that urine is a noninvasive biofluid that may represent blood proteins without requiring venipuncture. This would allow for more accessible, noninvasive diagnostics without requiring blood draw. Historically, the processing of multiple biofluid proteomes is expensive and time consuming, which limits clinical applicability. In this study, we use a high-throughput method to measure the relationship between urine and plasma proteomes, specifically comparing how urine may represent blood as a surrogate biofluid. By characterizing the representation of blood markers in urine, we aim to better understand and measure disease less invasively.

METHODS:
We measured urine and plasma from a cohort of 15 paired urine and plasma samples. Blood and urine samples were collected within 5 minutes of each other to ensure true pairing. Samples were processed in parallel using a ThermoFisher KingFisher Flex and were run on an Orbitrap Astral mass spectrometer.

RESULTS:
In our combined samples, we observed a total of 887 proteins in plasma and 3500 proteins in urine. Of these proteins, 722 overlapped across biofluids. Within individual samples, up to 88.1% of plasma proteins were also observed in urine (mean: 53.1%, range: 27-88.1%). In addition to the overlapping proteins, 2778 proteins were uniquely observed in urine compared to 165 proteins unique to plasma.

DISCUSSION:
Our study demonstrates that urine may represent a subset of the plasma proteome. This supports that urine may reflect circulating proteins, presenting an opportunity for clinical measurements without requiring venipuncture. Proteins that overlap between biofluids should be evaluated depending on disease for biological relevance to determine if urine is a suitable surrogate measurement for current blood markers. Additionally, the proteins observed in urine should be evaluated for disease-specific protein profiles which can be noninvasively measured and may be more holistic than individual blood markers. Our rapid measurement of urine and plasma in parallel enables the opportunity for downstream clinical implementation. Ongoing work will expand this dataset and further investigate how to leverage these biofluids for more systemic clinical applications. These initial findings provide a foundation for evaluating urine as a noninvasive biofluid for proteomic measurement of circulating proteins.