Abstract: TH-PO888
Procurement Retardation Improves Organ Recovery
Session Information
- Transplantation: Donation and Access
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Samson, Chloé, INSERM U1155, Paris, France
- Drouin, Sarah, INSERM U1155, Paris, France
- Buob, David, Assistance Publique - Hopitaux de Paris, Paris, France
- Hadchouel, Juliette, INSERM U1155, Paris, France
- Galichon, Pierre, INSERM U1155, Paris, France
Group or Team Name
- Mécanismes de l'insuffisance rénale aigüe et réparation.
Background
The conditioning of the donor is crucial to avoid delayed graft function (DGF), which occurs in nearly 30% of cases and is associated with graft loss. A third of brain-dead donors have a recovered cardiac arrest (RCA), thus leading to a first episode of renal ischemia before procurement. Even if ischemia is known to be deleterious, studies conducted so far did not find an association between the donor's RCA and DGF. We hypothesize that the time interval (TRCA) between the RCA (1st ischemia) and the graft's procurement (2nd ischemia) could influence the function and survival of the graft. Using the French CRISTAL database, we found that a TRCA shorter than 3 days is associated with an increased risk of DGF.
Several data suggest that proliferative cells are more sensitive to stress than non-proliferative ones. Given that an acute injury induces the proliferation of tubular cells, a procurement occurring during the proliferative phase of the tubular epithelium induced by the RCA-mediated ischemia could favor DGF. We used a mouse model to test this hypothesis and identify mechanisms responsible for the increased risk of DGF after an 'early' 2nd ischemia.
Methods
To mimic the situation of a donor with RCA, we performed two renal ischemias separated by either 2 or 5 days ('early' and 'late' 2nd ischemia), using a vascular occluder we recently developed. We evaluated the Glomerular Filtration rate (GFR) 24h after each ischemia by measuring the transcutaneous excretion kinetics of FITC-sinistrin (MediBeacon®). The histological analysis was carried out 24h after the 2nd ischemia by evaluating (i) the tubular injury and (ii) the cellular response using markers of proliferation (BrdU) and cell death (TUNEL).
Results
Comparably to the human data, the GFR following an early 2nd ischemia is lower than after a late 2nd ischemia. There was also a trend towards increased tubular lesions in the early group compared to the late one.
Our future goal is to examine the effects of inhibiting proliferation after an early 2nd ischemia on the function and structure of the kidney (short & long-term after ischemias).
Conclusion
Our results suggest that delaying kidney procurement after RCA could ameliorate the function and survival of the graft. Given that it concerns a frequent situation, our study could improve the quality of grafts by recommending an optimal time interval for procurement after an RCA.
Funding
- Private Foundation Support