Abstract: FR-PO907
Accelerated suPAR-Mediated Kidney Disease in the Solitary Functioning Kidney
Session Information
- Glomerular Diseases: Podocyte Biology - II
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1204 Podocyte Biology
Authors
- Wang, Xuexiang, Rush University Medical Center, Chicago, Illinois, United States
- Li, Jing, Rush University, Chicago, Illinois, United States
- Zhu, Ke, Rush University Medical Center, Chicago, Illinois, United States
- Samelko, Beata, Rush University Medical Center, Chicago, Illinois, United States
- Garrett, Michael R., University of Mississippi Medical Center, Jackson, Mississippi, United States
- Wei, David Changli, Rush University, Chicago, Illinois, United States
- Reiser, Jochen, Rush University Medical Center, Chicago, Illinois, United States
Background
Kidney mass and number of functioning nephrons are determinants of renal long-term health. Single functioning kidney (SFK) is a rare disease (1:1500 at birth) resulting in early onset chronic kidney disease (CKD) in over 50% of those affected. Similarly, kidney donors may have an increased risk for future CKD. The underlying mechanisms are not clear. The soluble urokinase receptor (suPAR) is an immune-derived circulating factor implicated in pathogenesis and prediction of CKD incidence and progression. We hypothesized that SFK condition could be more sensitive to increased suPAR levels and examined 3 different rodent models of SFK.
Methods
Uninephrectomy and sham surgeries were performed on C57B/6 mice, suPAR transgenic/knockout models or littermate controls. The minipumps with different concentrations of LPS were implanted subcutaneously. Proteinuria and suPAR were followed for 4 weeks. In congenital SKF rat model (HSRA), the recombinant human suPAR protein was injected intravenously into HSRA single kidney rats (HSRA-S) and two-kidney controls (HSRA-C). Proteinuria and beta3 integrin activity were assessed.
Results
Urinary protein slowly increased in nephrectomized suPAR transgenic mice, while the littermate controls with nephrectomy showed no change. LPS infusion resulted in increased level of serum and urine suPAR in C57B/6 mice. Interestingly, SFK models had a higher serum suPAR and substantially higher proteinuria, compared to the sham two-kidney groups. In contrast, uPAR deficient SFK mice were protected from LPS induced proteinuria. HSRA-S rats revealed an increase of proteinuria compared to HSRA-C after the recombinant human suPAR injection. The activity of the suPAR receptor beta3 integrin was increased in the kidney of HSRA-S rats following administration of suPAR.
Conclusion
Increased circulating suPAR levels, either induced by LPS, or from suPAR transgenic models or extrinsically injected, induce proteinuria in uninephrectomized mice or congenital SFK rats, when compared to their two-kidney controls. These findings suggest the importance of suPAR in SFK, possibly in kidney donors and support findings that suPAR cause declined renal function. Monitoring circulating suPAR levels might be important in understanding the pathogenesis and risk-control for patients who are born with or remain having only one functional kidney.
Funding
- Clinical Revenue Support