Abstract: SA-PO111
Proteomic Analysis of the Tubulointerstitium Characterizes Extracellular Matrix Changes in Acute Tubular Necrosis
Session Information
- AKI: Mechanisms - AKI-CKD Transition
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Satoskar, Anjali A., Ohio State University Medical Center, Columbus, Ohio, United States
- Shapiro, John P., Ohio State University Medical Center, Columbus, Ohio, United States
- Merchant, Michael, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Klein, Jon B., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Nadasdy, Tibor, Ohio State University Medical Center, Columbus, Ohio, United States
- Rovin, Brad H., Ohio State University Medical Center, Columbus, Ohio, United States
- Parikh, Samir V., Ohio State University Medical Center, Columbus, Ohio, United States
Background
Acute tubular necrosis (ATN) is the most common form of acute kidney injury (AKI) in the hospital setting. Urine proteomic analyses have been extensively performed in AKI, but the kidney proteome has largely been unexplored. Here, we performed unbiased proteomics on the tubuloniterstitium (TI) from kidney biopsies with ATN to identify kidney specific proteomic signatures that characterize ATN.
Methods
Laser microdissection was performed on FFPE kidney biopsy tissue from 8 ATN and 8 living transplant donor kidney biopsy controls (LTx). The TI was isolated and total protein was extracted and submitted for HPLC-MS/MS analysis using the Oribtrap Elite. Label free quantification followed by global normalization of spectral count data was performed. Proteomic expression of ATN was compared to LTx. Statistical significance was considered if 2-fold change and P<0.01.
Results
All patients had biopsy proven ATN. The average serum creatinine in ATN was 5.7mg/dl (SD: ± 2.7). Overall, 86 proteins were upregulated and 44 downregulated in ATN compared to LTx. The top upregulated markers included extracellular matrix (ECM) proteins implicated in AKI to CKD transition, ER stress proteins, and wound repair proteins (Figure 1). Meanwhile, transport, metabolism, and mitochondrial markers were suppressed. Pathway analysis revealed activation of remodeling of epithelial adheren junctions, acute phase response signaling, and coagulation and suppression of metabolic pathways.
Conclusion
Kidney proteomic evaluation demonstrates overexpression of ECM proteins in ATN that previously have been implicated in CKD progression and may reflect AKI to CKD transition. These markers could serve as novel therapeutic targets to arrest injury early and prevent progression to chronic kidney disease.
Figure 1. Markers overexpressed in ATN compared to controls
Funding
- NIDDK Support