Abstract: TH-PO1112
Donor Nephrectomy Selectively Increases Proximal Tubular Proteins in Urinary Vesicles
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
- Blijdorp, Charles J., Erasmus Medical Center, Rotterdam, Netherlands
- Severs, David, Erasmus Medical Center, Rotterdam, Netherlands
- Budde, Ricardo, Erasmus Medical Center, Rotterdam, Netherlands
- Hoenderop, Joost, Radboud university medical center, Nijmegen, Netherlands
- Bindels, René J., Radboud university medical center, Nijmegen, Netherlands
- Cuevas, Catherina A., Erasmus Medical Center, Rotterdam, Netherlands
- Zietse, Robert, Erasmus Medical Center, Rotterdam, Netherlands
- Hoorn, Ewout J., Erasmus Medical Center, Rotterdam, Netherlands
Background
Donor nephrectomy causes hyperfiltration and hypertrophy of the remaining kidney. Uninephrectomy in rats causes a selective increase in proximal tubular proteins. Accordingly, we hypothesize that human donor nephrectomy increases proximal tubular proteins.
Methods
Nineteen kidney donors were included in this study. Kidney volume was calculated from CT scans prior to donation. Urine was collected prior to and three months after donor nephrectomy. Urinary extracellular vesicles (uEVs) were isolated and used as non-invasive read-out for renal tubular protein abundance. uEVs were quantified using nanoparticle tracking analysis. The following proteins were analyzed in uEVs using ultracentrifugation and immunoblotting: NHE3, NaPi-IIa and cubilin (proximal tubule), NKCC2 (thick ascending limb), NCC (distal convoluted tubule), and AQP2 (collecting duct). Relative protein abundance was expressed per remaining kidney volume.
Results
Donor nephrectomy reduced kidney volume by 50±3%, creatinine clearance by 38±10%, and uEV excretion by 20%. The relative abundance of proximal tubular proteins in uEVs increased significantly, whereas no change occurred in distal nephron proteins (Figure).
Conclusion
Donor nephrectomy selectively increases proximal tubular proteins in uEVs. This may be due to hyperfiltration and hypertrophy occurring in this segment. It may also explain why a kidney volume reduction of ~50% is accompanied by a decrease in uEV excretion of only 20%. These results provide insight in the changes after kidney donation and are relevant when analyzing uEVs in kidney donors.
Funding
- Private Foundation Support