Kidney Week

Abstract: FR-PO930

Characterization of the Urine Proteome in 769 Patients with Early-Stage CKD

Session Information

• CKD Epidemiology, Risk Factors, Prevention - II
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Meier, Marisa Dorothea, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany

Marisa Dorothea Meier,

• Li, Yong, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany

Yong Li,

• Borisov, Oleg, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany

Oleg Borisov,

• Uluvar, Burulça, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany

Burulça Uluvar,

• Kottgen, Anna, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany

Anna Kottgen,

• Haug, Stefan, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany

Stefan Haug,

Background

Analyses of urinary proteins aim to identify new biomarkers for early disease detection, prognosis and therapeutic response in patients with chronic kidney disease (CKD). Hence, we used the antibody-based Olink Explore 3072 platform to quantify 2925 proteins in urine samples from 769 participants of the German Chronic Kidney Disease (GCKD) study and present a comprehensive characterization of the urine proteome at unprecedented scale.

Methods

Proteins were quantified in urine samples from persons with eGFR >45 and ≤60 mL/min/1.73 m² and UACR <300 mg/g. Protein detectability was computed as percentage of samples with Normalized Protein Expression above protein-specific limits of detection. Urine dilution was corrected before association and correlation analyses. Plasma detectability of 1463 corresponding proteins (Olink 1536 panel) and comparisons to urine were based on >52,000 participants of the UK Biobank.

Results

In total, 1926 of 2925 (65.8%) proteins had detectability >10% in urine. Of these, 593 (20.3%) were highly detectable (>80%), showing a strong overrepresentation for proteins from extracellular exosomes and extracellular regions. Highly detectable urine proteins were enriched for specific expression in liver, placenta, lung, and kidney, and for molecular functions as proteolytic enzymes or cell adhesion proteins. We found significant associations with participant characteristics for 342 urine proteins, including sex (268 proteins, e.g., prostate-specific MSMB and KLK3 were higher in men), age (20 proteins, e.g. RGMA, CILP) and BMI (54 proteins, e.g. IL1RN, IL1A). Correlation analyses revealed multiple clusters of co-regulated proteins (e.g. AZU1, PRTN3, MPO, all components of azurophilic granules in neutrophils). Compared to plasma, 16 of 1463 proteins (1.1%) had significantly higher detectability in urine, 105 (7.2%) were equally detectable, and 1342 (91.7%) had lower detectability.

Conclusion

The Olink Explore 3072 technology is suitable for urine proteomics with large sample sizes, and yields biologically plausible correlations and associations. The obtained information about detectability, composition and phenotypic associations of the urine proteome represents a basis for biomarker discovery, and facilitates future, more targeted studies in CKD and other diseases.

Funding

• Government Support – Non-U.S.