Abstract: TH-PO1109
Circular RNA in Urine-Liquid Biopsy Biomarker of Acute Rejection in Kidney Transplantation
Session Information
- Transplantation: Clinical - Predictors of Outcomes - Biomarkers and Beyond
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1902 Transplantation: Clinical
Authors
- Kölling, Malte, University Hospital Zurich, Zurich, Switzerland
- Haddad, George, University Hospital Zurich, Zurich, Switzerland
- Kistler, Andreas D., Frauenfeld Cantonal Hospital, Frauenfeld, Switzerland
- Seeger, Harald, University Hospital Zurich, Zurich, Switzerland
- Huebel, Kerstin, University Hospital Zurich, Zurich, Switzerland
- Haller, Hermann G., Hannover Medical School, Hannover, Germany
- Wuthrich, Rudolf P., University Hospital Zurich, Zurich, Switzerland
- Lorenzen, Johan, University Hospital Zurich, Zurich, Switzerland
Background
Circular RNAs (circRNAs) are long non-coding RNA transcripts with strong gene regulatory function. Their circular structure guarantees stable detection in blood. We hypothesized that circRNAs are detectable in urine as well and serve as biomarker of acute T cell-mediated kidney allograft rejection.
Methods
A global urinary circRNA expression analysis was performed in patients with acute rejection compared to patients without rejection. Differentially concentrated circRNAs were validated in patients with acute rejection (n=62), in stable transplant patients (control, n=18) and rejection dependent concentrations were additionally analyzed after successful anti-rejection therapy (n=10). Biomarker specificity was verified in stable transplant patients with urinary tract infection (disease control, n=13).
Results
A distinct urinary circRNA transcriptome signature identified patients with acute rejection. CircRNAs hsa_circ_0001334 and hsa_circ_0071475 were strongly altered and thus validated in the whole cohort. Increased hsa_circ_0001334 concentrations were specifically confirmed in patients with acute rejection and returned to base level after anti-rejection therapy. Hsa_circ_0001334 showed promising biomarker value and prognostic potential in predicting higher decline of creatine clearance after one year of transplantation.
Conclusion
In conclusion, patients with acute rejection were identified by a specific urinary circRNA transcriptome signature and circRNA hsa_circ_0001334 was discovered as novel non-invasive diagnostic and prognostic biomarker of acute T cell-mediated kidney allograft rejection. Measuring concentrations of circRNAs in urine might thus serve as novel liquid biopsy in kidney transplant patients.