Abstract: SA-PO784
CKD Is Associated with a Pro-Angiogenic and Inflammatory Profile Even in Post-Transplant CKD
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Jalal, Diana I., University of Iowa, Iowa City, Iowa, United States
- Renner, Brandon, University of Colorado Denver Med Campus, Aurora, Colorado, United States
- Ten eyck, Patrick, University of Iowa, Iowa City, Iowa, United States
- Laskowski, Jennifer, University of Colorado School of Medicine, Greenwood Village, Colorado, United States
- Cooper, James E., University of Colorado at Denver, Denver, Colorado, United States
- Sun, Mingyao, University of Iowa, Iowa City, Iowa, United States
- Attanasio, Massimo, University of Iowa, Iowa City, Iowa, United States
- Thurman, Joshua M., University of Colorado School of Medicine, Greenwood Village, Colorado, United States
Background
Cardiovascular disease (CVD) is the most common cause of death in native and post-transplant chronic kidney disease (CKD). Circulating microparticles (MP) are increased in CKD and may reflect vascular injury and inflammation, important non-traditional risk factors for CVD. Here, we sought to identify novel biomarkers of vascular injury and inflammation common in both native and post-transplant CKD.
Methods
Proteomic analyses were conducted on plasma and MP of 9 healthy controls, 9 stage 3/4 native CKD patients, and 9 stage 3/4 post-transplant CKD patients. Somalogic SOMAscan assay, a highly sensitive assay that uses aptamers to quantify >1,300 proteins, was used. Ingenuity pathway analyses (IPA) were conducted.
Results
We identified 44 plasma proteins common to both native and post-transplant CKD vs healthy controls; the most significant being angiogenic proteins. IPA indicated Ephrin receptor signaling, serine biosynthesis, and transforming growth factor (TGF)-β as the top pathways activated in both CKD groups. The MP analyses indicated higher levels of 18 proteins common in both native and post-transplant CKD patients vs healthy controls. These proteins included cystatin C, β2-microglobulin, and renin precursor protein. Biomarkers of inflammation and fibrosis were most pronounced with IPA indicating acute phase response, insulin-like growth factor-1, tumor necrosis factor-α, and interleukin-6 signaling activation.
Conclusion
We have identified new putative pathways of vascular injury and inflammation in CKD. Pathways of angiogenesis and inflammation were significantly activated in CKD patients’ plasma and MPs, respectively. Considering the high levels of MP renin precursor protein, the MPs most likely originated in the kidney. The activated pathways common in both native and post-transplant CKD suggest similar mechanisms of CVD in both groups of CKD.
Funding
- NIDDK Support