Abstract: TH-PO1110
Longitudinal and Cross-Sectional Analysis of Kidney Transplant Urine mRNAs Reveals Glomerular Disease as an Important Driver of Long-Term Graft Loss
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
- Naik, Abhijit S., University of Michigan, Ann Arbor, Michigan, United States
- Samaniego-Picota, Milagros D., Henry Ford Health Services, Detroit, Michigan, United States
- Cibrik, Diane Marie, University of Kansas Hospital, Parkville, Missouri, 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
Biopsies from failing allografts (El-Zoghby) and longitudinal protocol biopsies in two studies (Nankivell; Stegal) suggest that glomerular disease (GD) is associated with late graft loss. In a10yr study Stegal reported GD to be more prevalent than IFTA. To understand why kidney transplants fail over time, we utilized nephron segment specific urine pellet mRNA markers to enable non-invasive analysis of injury patterns
Methods
Longitudinal and cross sectional urine samples covering 20years post-TP for all comers were collected. Two podocyte markers (podocin, nephrin), a distal tubular/collecting duct marker (aquaporin2) and marker of innate immune/profibrotic activity (TGFBeta1) were measured in spot urine samples and normalized to creatinine. Baseline 2kidney (2K) values for 4 markers were obtained from 98 healthy controls and used to derive 1K normal values.
Results
380 recipients provided 1997 urine pellets. All markers increased immediately after TP but downtrended towards expected ranges. Over 20yrs there was a steady increase in both podocyte markers (UPod:CR,UNeph:CR) compatible with increasing podocyte detachment rate. The ratio of podocin to nephrin (UPod:Neph) a marker of podocyte hypertrophic stress increased markedly after TP, and remained elevated above 2K control. Downstream tubular injury marker (Aqp:CR) remained elevated in the short-intermediate term compatible with tubule-interstitial injury but by 3years decreased to 2K level. The ratio of the glomerular to tubular marker (UPod:Aqp2) continued to increase after TP reflecting increasingly glomerular vs. tubular injury. Urine pellet TGFbeta1CR remained elevated above 2K level suggesting ongoing TP injury.
Conclusion
Urine pellet mRNA data are compatible with long-term protocol biopsy data suggesting that GD is an important driver of long-term kidney allograft failure.
Funding
- NIDDK Support