Abstract: TH-PO1157
Living Kidney Donation Is Accompanied by Persistently Increased Urine Pellet Nephrin mRNA in the First Year After Donation
Session Information
- Transplantation: Clinical - Pretransplant Management
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
- Naik, Abhijit S., University of Michigan, Ann Arbor, Michigan, United States
- Cibrik, Diane Marie, University of Kansas Hospital, Parkville, Missouri, United States
- Samaniego-Picota, Milagros D., Henry Ford Health Services, Detroit, Michigan, United States
- Wang, Su Qing, University of Michigan, Ann Arbor, Michigan, United States
- Chowdhury, Mahboob A., University of Michigan, Ann Arbor, Michigan, United States
- Wiggins, Roger C., University of Michigan, Ann Arbor, Michigan, United States
Background
Living kidney donation is associated with increased long-term risk of CKD/ESRD post-donation. Diabetes and hypertension are reported to be associated with ESRD. The remaining kidney is rarely biopsied and thus mechanisms behind progression remain unproven. Parallel data from uni-nephrectomized rat models shows podocyte hypertrophic stress, detachment and depletion, progressive proteinuria and FSGS. While proteinuria is common among donors vs. matched non-donors, it is often low grade
Methods
We used urine pellet nephron segment specific mRNA markers expressed per creatinine to understand biology of the remaining kidney early post-donation. Donor urine samples were divided by time of collection. Group 0, before donation; Group 1, 1-2days post donation; Group 2, 10-14days and Group 3, 6-12months post donation. Linear mixed model clustering for patients was used to assess trends across two podocyte specific markers (podocin, nephrin), a distal collecting duct marker (Aqp2) and a marker of innate immunity/profibrotic activity (TGFbeta1) and proteinuria
Results
72 donors provided 178 urine samples for the analysis. Figure 1 reveals that proteinuria and podocin, Aqp2 and TGFbeta1 mRNAs were increased immediately post donation (referenced to Group 0) but normalized by 2weeks post-donation. Nephrin remained significantly increased over the first year.
Conclusion
All markers showed evidence for hypertrophic kidney stress immediately post-TP. Sustained increased urinary nephrin mRNA in living donors after TP may represent hypertrophic adaptation to the single kidney state requiring up-regulation of nephrin to maintain increased filtration slit length. Whether higher level nephrin mRNA expression is related to future risk of progressive kidney disease remains to be tested.
Coefficient Plot demonstrating change in 4 markers at Group1, 2 and 3 ( relative to time 0)
Funding
- NIDDK Support