Kidney Week

Abstract: FR-PO454

Analysis of the Plasma Proteome Reveals Dysregulation of Molecular Pathways in Patients with Stage 4 CKD

Session Information

• CKD: Risk Factors for Incidence and Progression - II
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Chronic Kidney Disease (Non-Dialysis)

• 301 CKD: Risk Factors for Incidence and Progression

Authors

• Kulikowski, Ewelina, Resverlogix Corp, Calgary, Alberta, Canada

Ewelina Kulikowski,

• Wasiak, Sylwia, Resverlogix Corp, Calgary, Alberta, Canada

Sylwia Wasiak,

• Tsujikawa, Laura, Resverlogix Corp, Calgary, Alberta, Canada

Laura Tsujikawa,

• Halliday, Christopher, Resverlogix Corp, Calgary, Alberta, Canada

Christopher Halliday,

• Stotz, Stephanie, Resverlogix Corp, Calgary, Alberta, Canada

Stephanie Stotz,

• Gilham, Dean, Resverlogix Corp, Calgary, Alberta, Canada

Dean Gilham,

• Jahagirdar, Ravi, Resverlogix Corp, Calgary, Alberta, Canada

Ravi Jahagirdar,

• Kalantar-Zadeh, Kamyar, University of California Irvine, School of Medicine, Orange, California, United States

Kamyar Kalantar-Zadeh,

• Robson, Richard Austin, CHristchurch Clinical Studies Trust, Christchurch, New Zealand

Richard Austin Robson,

• Sweeney, Michael, Resverlogix Inc., San Francisco, California, United States

Michael Sweeney,

• Johansson, Jan O., Resverlogix Inc., San Francisco, California, United States

Jan O. Johansson,

• Wong, Norman C. W., Resverlogix Corp, Calgary, Alberta, Canada

Norman C. W. Wong,

Background

Chronic kidney disease (CKD) is associated with progressive loss of renal function. To gain insight into molecular mechanisms and biological consequences of pathway dysregulation in CKD, plasma proteome profiling of stage 4 CKD patients was performed using a novel somamer-based approach coupled to bioinformatics.

Methods

Eight subjects with stage 4 CKD not on dialysis (mean eGFR=20 ml/min/1.73m²) and eight matched control subjects (mean eGFR=78.5 ml/min/1.73m²) participated in the study. Plasma samples were collected for analysis with the SOMAscan® 1.3K platform, which detects 1305 proteins in a multiplexed, sensitive and reproducible manner. Proteomics data were analysed with Ingenuity Pathway Analysis (IPA®).

Results

SOMAscan® proteomic analysis of plasma from CKD versus control subjects identified 289 differentially expressed proteins (difference>10%, p<0.05). 191 of those proteins were upregulated by more than 50% in CKD plasma relative to controls. Many of the enriched markers correlate with CKD progression, including cystatin C, B2M, LCN2, LFABP and FGF23. Other differentially expressed proteins include cytokines and their soluble receptors, adhesion molecules, metalloproteases, complement, coagulation and fibrinolytic factors. IPA® bioinformatics of the plasma proteome confirmed an upregulation of pathways known to be activated in CKD such as the inflammatory and immune response, endothelial dysfunction, thrombosis, renin-angiotensin system, calcification and oxidative stress.

Conclusion

This study provides an exhaustive list of plasma proteins that are dysregulated in stage 4 CKD. In combination with pathway analysis, this CKD plasma proteome contributes new knowledge of molecular processes that accompany CKD and potential new disease markers.