Abstract: SA-PO791
Downregulation of Renoprotective Factors Is Associated with Outcome in CKD
Session Information
- CKD: Epidemiology, Risk Factors, Prevention - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1901 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Perco, Paul, Medical University Innsbruck, Innsbruck, Austria
- Rudnicki, Michael, Medical University Innsbruck, Innsbruck, Austria
- Kerschbaum, Julia, Medical University Innsbruck, Innsbruck, Austria
- Leierer, Johannes, Medical University Innsbruck, Innsbruck, Austria
- Mayer, Gert J., Medical University Innsbruck, Innsbruck, Austria
Background
An imbalance of nephroprotective factors and renal damaging molecules contributes to development and progression of chronic kidney diseases. Molecules with renoprotective properties and capacity to induce renal repair might serve as biomarkers, drug targets as well as therapeutic options themselves. In this study we determined the potential of renoprotective factors to predict disease progression in a set of chronic kidney disease (CKD) patients.
Methods
Gene expression profiles were determined for 197 previously published proteins with renoprotective properties in renal biopsies of 63 CKD patients with different disease diagnoses. The statistical analysis of microarray method was used to identify downregulated factors in the group of progressive patients as compared to those showing a stable course of disease with a false discovery rate < 5%. Progression was defined as reaching end-stage renal disease or doubling of serum creatinine. Significance of renoprotective factors to predict course of disease was in addition analysed in time-to-event analysis using Kaplan Meier curves and log-rank statistics. Cox regression models were used to adjust for the clinical parameters estimated glomerular filtration rate (eGFR) and diagnosis type.
Results
The six renoprotective factors dicarbonyl and L-xylulose reductase (DCXR), epidermal growth factor (EGF), glutathione S-transferase mu 1 (GSTM1), kininogen 1 (KNG1), nitric oxide synthase 3 (NOS3), and uromodulin (UMOD) were significantly downregulated in the group of progressive patients and were also significantly associated with outcome in time to event analysis. DCXR (p-val = 0.0277), EGF (p-val = 0.0264), GSTM1 (p-val = 0.0039), and KNG1 (p-val = 0.0372) remained significant after adjustment for eGFR and diagnosis in Cox regression analysis thus being independently associated with outcome. This is to our knowledge the first study describing the prognostic potential for DCXR in human CKD samples with literature evidence already being available for the other three markers showing significance in our cohort.
Conclusion
We identified a set of four renoprotective factors being downregulated in progressive CKD patients on the mRNA level and independently associated with disease outcome.
Funding
- Government Support - Non-U.S.