Kidney Week

Abstract: SA-PO920

Progressive Changes in Urine Extracellular Vesicle Molecular Signatures Predict Phase of AKI

Session Information

• Pathology and Lab Medicine - 2
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

• 1800 Pathology and Lab Medicine

Authors

• Ng, Monica S., Kidney Health Service, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Monica S. Ng, MBBS, PhD

• Chiang, Sophie Chin-Ya, Kidney Health Service, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Sophie Chin-Ya Chiang

• Wang, Xiangju, Kidney Health Service, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Xiangju Wang

• Healy, Helen G., Kidney Health Service, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Helen G. Healy, MBBS, PhD

• Kassianos, Andrew J., Kidney Health Service, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Andrew J. Kassianos, PhD

Background

Acute kidney injury (AKI) carries risks of severe complications including kidney failure and death. Urine extracellular vesicles (uEVs) released by cells in the urinary tract may have biomarker potential for assessing phase of AKI.

Methods

50ml urine collected from people with evolving (n=3) and recovering (n=3) stage 3 AKI. Evolving AKI group had rise in serum creatinine and recovering AKI group had improving serum creatinine. uEVs were isolated using sequential centrifugation and size exclusion chromatography. uEVs were confirmed using electron microscopy and uEV related proteins were confirmed with mass spectrometry. uEVs were stained for cell source (podocyte: podocin; mesangial: CD90; endothelial: CD31; tubular: mucin-1; proximal tubule: CD10, CD13) and inflammatory cytokine receptors (interleukin (IL)-1R1, IL-1R2, IL-6R, IL-2R). Stained uEVs were measured by multiparametric spectral flow cytometry. Counts were normalised to urine creatinine and compared using t-tests with correction for multiple comparisons.

Results

People with recovering AKI had increased uEVs compared to people with evolving AKI (mean: 7.89 x 10⁶ uEVs/μmol creatinine vs 1.64 x 10⁶ uEVs/μmol creatinine, p=0.048). Compared to people with evolving AKI, people with recovering AKI excreted more uEVs expressing CD90 (mean: 2,605 uEVs/μmol creatinine vs 407 uEVs/μmol creatinine, p=0.039), CD31 (mean: 8,833 uEVs/μmol creatinine vs 2,772 uEVs/μmol creatinine, p=0.012), mucin-1 (mean: 464,330 EVs/μmol creatinine vs 81,535 uEVs/μmol creatinine, p=0.015), IL-1R1 (mean: 8,481 uEVs/μmol creatinine vs 727 uEVs/μmol creatinine, p=0.030) and IL-2R (mean: 58,799 uEVs/μmol creatinine vs 1,671 uEVs/μmol creatinine, p=0.003) [Fig 1].

Conclusion

People with recovering AKI excrete more uEVs from mesangial, endothelial and tubular cells compared to people with evolving AKI. The inflammatory signatures of uEVs have biomarker potential for profiling AKI phase.

Fig 1-Concentration of uEVs expressing different surface markers from people with evolving and recovering AKI. * p<0.05, ** p<0.01.

Funding

• Government Support – Non-U.S.