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Abstract: SA-PO797

Urinary Proteomics in CKD Associated with Glomerular Endothelial Cell Injury

Session Information

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Kim, Ji Eun, Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Jeong, Jinseon, Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Moon, Jong joo, Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Kim, Yong Chul, Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Yang, Seung Hee, Kidney Research Institute, Seoul National University, Seoul, Korea (the Republic of)
  • Kim, Yon Su, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
Background

A number of studies have been conducted on the identification of urinary proteomics associated with the progression of chronic kidney disease (CKD). In the course of CKD, any injury to the glomerular structure is likely to affect the glomerular endothelial cell. In this study, we sought to identify proteomic markers that increase in CKD with endothelial cell injury.

Methods

Label-free quantitative proteomic analysis based on liquid chromatography- tandem mass spectrometry (LC-MS/MS) was performed on urine samples obtained from 9, 11, and 10 patients in CKD stage 1, 3 and 5, respectively. Quantitative proteomic analysis based on Tandem mass tag (TMT) was also performed for primary cultured glomerular endothelial cells (GECs) before and after inducing hypoxia injury through maintenance in hypoxia chamber for 24 hours. Selection of differentially expressed proteins (DEPs) was based on false discovery rate-adjusted p-value <0.05.

Results

The mean estimated glomerular filtration rate of patients with CKD stages 1, 3, and 5 were 110.1 + 17.9, 43.2 + 12.5, and 10.5 + 3.0, respectively. We identified 65, 198, and 650 DEPs between CKD 1 and CKD 3, between CKD 3 and CKD 5, and between CKD 1 and CKD 5, respectively, when the urinary proteins were identified in these CKD patients. When comparing the proteins expressed before and after hypoxia injury in the GEC cell, we identified 4032 DEPs in the first experimental set and 3194 DEPs in the second set. Only 8 of these proteins showed significant results in both urine of CKD patients and endothelial cells. Among these 8, there were only 5 significant results between CKD 3 and 5 and between CKD 1 and 5, and there were no significant results between CKD 1 and 3. Among the significant proteins, IGFBP3, APOL1, and PROS1 increased more than 1.5 fold with hypoxia injury on GEC and increasing CKD stages, whereas HILPDA and MUC1 increased with GEC injury and decreased with increasing CKD stages.

Conclusion

We have identified specific urinary proteins that change with endothelial cell injury and CKD progression, and further analysis of the diagnostic value of these proteins for chronic renal failure and endothelial cell damage is needed.