Improving kidney preservation: HEMO2Life® supplementation rescues ischemia reperfusion injury
Résumé
Purpose: Static cold storage is a simple and inexpensive protocol for graft preservation. However, as transplant centers are driven to accept extended criteria donors, more susceptible to ischemia reperfusion injury (IRI), this protocol must be optimized. We tested the protection efficacy of supplementing UW with a new oxygen transporter developed for organ preservation, HEMO2life®.
Methods: Kidneys from Large White pigs were collected and preserved in UW for 24h before autotransplantation. Graft function was monitored, evaluations with transcriptomics and histological analysis were performed 1 month post reperfusion.
Results: Kidneys preserved with HEMO2life® presented an early recovery of diuresis (day 1 vs day 3) and function recovery was swifter with a lower creatinine peak (150.0±10.1 at day 1vs. 1250.3±69.9 at day 3). Moreover, histological evaluation revealed less IRI related lesions to the tubules in the HEMO2life® grafts. One month post transplant, graft histology was better in HEMO2life® grafts in regards to immune cell infiltration and tubulitis. Real time PCR analysis revealed that these grafts displayed lower expression of TLR4 and TGFβ, indicating lower innate immunity activation and activation of fibrosis, respectively. Moreover, HEMO2life® graft showed higher expression of FoxP3 mRNA, suggesting regulation of immune response. We are currently conducting long term analysis of HEMO2life® supplementation by immunohistofluorescence, real time PCR and proteomics.
Conclusions: Improving current static preservation protocols with HEMO2life® supplementation provided important benefits to graft outcome, both in the short and the long term. As only one additive to the preservation solution is needed, this strategy is easily translatable to the clinic and could critically improve graft quality as well as patients quality of life.