Kidney Week

Abstract: TH-OR80

CER-001, a Recombinant HDL, Modulates Ischemia/Reperfusion Injury (IRI) in Hypothermic (HMP) and Normothermic Perfusion (NMP) Solutions Through pAKT/eNOS Activation

Session Information

• Mechanisms and Single-Cell Transcriptional Profiles in Transplant Rejection and Ischemia Reperfusion Injury
  November 02, 2023 | Location: Room 115, Pennsylvania Convention Center
  Abstract Time: 05:51 PM - 06:00 PM

Category: Transplantation

• 2101 Transplantation: Basic

Authors

• Franzin, Rossana, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy

Rossana Franzin, PhD

• Stasi, Alessandra, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy

Alessandra Stasi,

• Fiorentino, Marco, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy

Marco Fiorentino,

• Scalera, Irene, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy

Irene Scalera,

• Campioni, Monica, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy

Monica Campioni,

• Cimmarusti, Maria Teresa, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy

Maria Teresa Cimmarusti,

• Castellano, Giuseppe, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy

Giuseppe Castellano,

• Sallustio, Fabio, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy

Fabio Sallustio,

• Pontrelli, Paola, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy

Paola Pontrelli,

• Simone, Simona, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy

Simona Simone,

• Gesualdo, Loreto, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy

Loreto Gesualdo,

Background

The growing use of expanded criteria donor leads to urgent need for efficient organ reconditioning strategies.CER-001 (Abionyx), a HDL lipoprotein particle, has shown clinical anti-inflammatory and protective vascular efficacy.This study aims to evaluate to role of CER-001 supplementation in perfusion solution to modulate IRI.

Methods

In an experimental model of donation in cardiac death (DCD), after 60 minutes of warm ischemia, pig kidneys were subjected to standard cold storage(12h).Oxygenated hypothermic and normothermic renal perfusion were carried out by PerKidney system(Aferetica) for 4h.Perfused organs were divided into the CTRL and CER-001 groups (CER-001 0.4 mg/ml) and compared to organs stored on ice (SCS).Endothelial cells exposed to H₂O₂, C5a and CER-001 (50-100 ug/ml) were analyzed by cell proliferation assay, qPCR, Western blot and FACS.

Results

During HMP and NMP treatments, resistances (mmHg/ml/min TEND CER-001 0.404 vs CTRL 0.766, change from T0, p=0.24) and flows significantly improved in CER-001 perfused group. ELISA data on perfusates showed a reduction in MCP-1, TNFα (CER-001 vs CTRL, p<0.05). In the SCS group, the tubules appeared dilated, interstitium with infiltrate, the floccule detached from the Bowman capsule. The use of CER-001 induced a reduction in the gene expression of IL-6 and Endothelin-1 in the CER-001 vs CTRL group. Urinary proteinuria measured during NMP was significantly decreased in CER-001 group. WB analysis revealed that CER-001 promoted the SR-BI-pAkt-eNOS pathway, the signaling pathway that through the phosphorylation of eNOS Serine 1177 lead to release of protective nitric oxide (NO). In vitro, CER-001 prevents apoptosis, endothelial dysfunction as observed by MTT and CD31/eNOS expression and reduced the levels of marker of endothelial activation (ICAM and VCAM).

Conclusion

The use of CER-001 in the perfusion liquid counteracted vasocostriction and inflammation and improved renal resistance during kidney perfusion, thereby increasing pool of organ for transplant.