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Abstract: SA-PO1107

New Urine Biomarkers for Site-Unique Injuries in the Kidney

Session Information

Category: Pathology and Lab Medicine

  • 1502 Pathology and Lab Medicine: Clinical

Authors

  • Yamamoto, Keiko, Niigata University, Niigata, Japan
  • Miyazaki, Shigeru, Shinraku-en Hospital, Niigata, Japan
  • Yamamoto, Tadashi, Niigata University, Niigata, Japan

Group or Team Name

  • Biofluid Biomarker Center
Background

In kidney diseases, various sites, such as glomerulus and other sites are injured to appear functional impairments and symptoms varied according to the injured sites and its degree. We aimed to develop urine examination to obtain the kidney site-unique injuries by proteomic biomarker discovery. To select kidney site-unique proteins as candidates of urine biomarkers for these site injuries, various parts of the kidney sections were analyzed by proteomics. To validate usefulness of the biomarker candidates, we established antibody-based assays for measurement of these biomarker candidates in urine and examined relationship between the urine excretion and the degree of kidney injuries. Finally we could select several urine biomarkers for injuries at various parts such as the glomerulus, proximal tubule and interstitium.

Methods

Sections of human kidney parts (glomerulus, proximal tubule, distal tubule, collecting duct etc) were laser micro-dissected from formalin-fixed paraffin-embedded kidney sections and peptides were collected from these sections of kidney parts by the on-site direct digestion method for mass spectrometry (Orbitrap Fusion, Thermo Scientific). The proteomes of these kidney parts were compared each other and also with those of plasma and urine proteomes to select proteins, which were uniquely excreted from each site or part of the kidney. We established immunoassay system by using a surface plasmon resonance (SPR) device (ProteOn, Bio-Rad). Several site-unique urine proteins selected by proteomics: PRA2R1 and GPRC5C for glomerulus-, NPR1 for proximal tubule- and GGT5 for interstitium-injury) were quantitatively measured in urine samples from CKD patients (IgA nephropathy and diabetic nephropathy) by SPR for validation.

Results

Concentrations of the proteins increased significantly in urine with the stage of CKD: PRA2R1 and GPRC5C excretion in urine presumed to reflect the degree of glomerular injury, NPR1 to predict the proximal tubule reactions and GGT5 the interstitial expansion, indicating that these new urine biomarkers are useful for evaluation of kidney injuries more precisely as or more than the kidney biopsies or evaluation of kidney injuries more precisely.

Conclusion

Non-invasive urine tests for the new biomarkers may be beneficial for clinical quantitative evaluation of kidney site-unique injuries for precision medicine in the near future.

Funding

  • Commercial Support