Abstract: FR-PO784
Selectively Increased Urinary Endotrophin Levels in T-Cell Mediated Kidney Transplant Rejection
Session Information
- Transplantation: Clinical - Biomarkers
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Alkaff, Firas F., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
- Kremer, Daan, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
- Rasmussen, Daniel Guldager Kring, Nordic Bioscience, Herlev, Herlev , Denmark
- Tepel, Martin, Odense Universitetshospital, Odense, Syddanmark, Denmark
- Thaunat, Olivier, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes , France
- van den Heuvel, Marius C., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
- Berger, Stefan P., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
- Genovese, Federica, Nordic Bioscience, Herlev, Herlev , Denmark
- Karsdal, Morten Asser, Nordic Bioscience, Herlev, Herlev , Denmark
- van den Born, Jacob, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
- Bakker, Stephan J.L., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
Background
Endotrophin (ETP) is a proteolytic fragment of collagen VI α3 chain and involved in adipose tissue homeostasis. However, upon renal tissue remodeling, collagen VI is increased and ETP is released. In this study we evaluated whether plasma and/or urinary ETP is associated with graft rejection in kidney transplant recipients (KTR).
Methods
This is a cross-sectional study among KTR who are enrolled in TransplantLines Biobank and Cohort Study. Blood and urine were collected on the same day as the biopsy procedure. Plasma and urinary ETP were measured using Enzyme-Linked Immunosorbent Assay. Diagnosis of graft rejection was according to the BANFF classification at the time the biopsies were taken.
Results
See Table for results. KTR with indication biopsy showed increased plasma ETP and urinary ETP/Creatinine ratio (ECR). Among patients who underwent indication biopsy, both plasma ETP and ECR were significantly correlated with C-reactive protein, serum creatinine, and eGFR but not with urinary protein excretion. Further, those with T-cell mediated rejection (TCMR) had higher ECR but similar plasma ETP level. In the logistic regression analysis, ECR was significantly associated with TCMR, even after adjustment for age, sex, eGFR, and 24-hour protein excretion (OR per doubling 1.39, 95%CI = 1.08-1.78, p = 0.011).
Conclusion
Our findings show that in urine, but not in plasma, ETP is selectively increased in TCMR independent of kidney function and proteinuria, suggesting increased renal ETP release upon TCMR. Further studies focusing on T-cell specific cytokines in collagen VI synthesis needs to be done.
| Protocol biopsies (n = 17) | Indication biopsies (n = 110) | TCMR in indication biopsy (n = 36) | non-TCMR in indication biopsy (n = 74) | |
| Plasma ETP (ng/mL) | 10.8 [9.2-11.7] | 18 [14.1-26.1]* | 18.2 [14.6-25.8]* | 17.6 [13.6-26.6]* |
| ECR (ng/mmol) | 273 [214-573] | 2070 [421-7153]* | 4323 [1801-13106]*# | 918 [308-5892]* |
66% male, age 54±15 years, eGFR 33.3±17.7 mL/min/1.73 m2, median 13 [5-71] months after transplantation. *p<0.001 compared to protocol biopsies. #p=0.003 compared to non-TCMR.
Funding
- Commercial Support – Astellas BV, and Chiesi Pharmaceuticals BV