Background: The damage following ischaemia-reperfusion injury (IRI) after transplant seems to play a role on the pathogenesis of local (ischaemic cholangiopathy-IC) and remote organ (acute kidney injury-AKI) complications after liver transplantation (LT). Aim of the study was to evaluate this relationship. Methods: Sixty-two consecutive LT patients with common bile duct sample retrieved after liver graft reperfusion, before biliary anastomosis (2014–2015) were enrolled. The occurrence of post-tx IC was recorded and related to post-tx bile duct injury. The occurrence of AKI (KDIGO 2012 GL) in the first-week post- tx was also recorded. Histologic examination and immunohistochemistry of the common bile duct were conducted to evaluate bile duct injury (Biliary epithelial cell loss, Mural stroma necrosis, Inflammation, Peribiliary vascular plexus damage, Arteriolonecrosis, Thrombosis, Periluminal, and deep peribiliary glands damage), apoptosis, and proliferation of cholangiocytes in peribiliary glands. Results: Five patients (8.1%) developed IC (4 DCD, 1 DBD). The 4 DCD patients showed severe post-tx histological damage defined as combined damage of mural stroma (necrosis > 50%), perivascular plexus and peribiliary glands (p = 0.018), longer agonal phase (25 vs 16 min, p = 0.048), asystolic phase (34 vs 27 min, p = 0.039) and dWIT (59, vs 41 min, p = 0.015), higher post-tx peak AST (328 vs 55 min, p = 0.042). All the 5 IC patients, with median pre-tx creatinine 0.9 mg/dL, developed post-tx AKI (2 pts Stage 1, 1 pt Stage 2 and 2 pts Stage 3). No differences in apoptosis and proliferation were detected. Conclusion: The occurrence of IC is characterized by more severe damage related to the IRI and is more frequent in DCD patients. The development of AKI, despite normal pre-tx renal function in all these patients supports the hypothesis of a common pathogenetic mechanism mediated by IRI, that acts both at the local and remote organ level. The evaluation of VEGF and HIFs (under completion) will further clarify the underlying mechanisms. The study was supported by ESOT Grant.

Acute kidney injury in patients with ischaemic cholangiopathy post liver transplantation: the ischemia riperfusion injury as a common pathogenetic mechanism / Tinti, F; Umbro, L; Mancinelli, R; Franchitto, A; Onori, P; Gaudio, E; Muiesan, P; Hubscher, Sg; Mitterhofer, Ap. - In: TRANSPLANT INTERNATIONAL. - ISSN 0934-0874. - 32:S2(2019), pp. 423-423. ((Intervento presentato al convegno 19th Congress of the European Society for Organ Transplantation tenutosi a Copenhagen, Denmark.

Acute kidney injury in patients with ischaemic cholangiopathy post liver transplantation: the ischemia riperfusion injury as a common pathogenetic mechanism

Tinti, F;Umbro, L;Mancinelli, R;Franchitto, A;Onori, P;Gaudio, E;Mitterhofer, AP
2019

Abstract

Background: The damage following ischaemia-reperfusion injury (IRI) after transplant seems to play a role on the pathogenesis of local (ischaemic cholangiopathy-IC) and remote organ (acute kidney injury-AKI) complications after liver transplantation (LT). Aim of the study was to evaluate this relationship. Methods: Sixty-two consecutive LT patients with common bile duct sample retrieved after liver graft reperfusion, before biliary anastomosis (2014–2015) were enrolled. The occurrence of post-tx IC was recorded and related to post-tx bile duct injury. The occurrence of AKI (KDIGO 2012 GL) in the first-week post- tx was also recorded. Histologic examination and immunohistochemistry of the common bile duct were conducted to evaluate bile duct injury (Biliary epithelial cell loss, Mural stroma necrosis, Inflammation, Peribiliary vascular plexus damage, Arteriolonecrosis, Thrombosis, Periluminal, and deep peribiliary glands damage), apoptosis, and proliferation of cholangiocytes in peribiliary glands. Results: Five patients (8.1%) developed IC (4 DCD, 1 DBD). The 4 DCD patients showed severe post-tx histological damage defined as combined damage of mural stroma (necrosis > 50%), perivascular plexus and peribiliary glands (p = 0.018), longer agonal phase (25 vs 16 min, p = 0.048), asystolic phase (34 vs 27 min, p = 0.039) and dWIT (59, vs 41 min, p = 0.015), higher post-tx peak AST (328 vs 55 min, p = 0.042). All the 5 IC patients, with median pre-tx creatinine 0.9 mg/dL, developed post-tx AKI (2 pts Stage 1, 1 pt Stage 2 and 2 pts Stage 3). No differences in apoptosis and proliferation were detected. Conclusion: The occurrence of IC is characterized by more severe damage related to the IRI and is more frequent in DCD patients. The development of AKI, despite normal pre-tx renal function in all these patients supports the hypothesis of a common pathogenetic mechanism mediated by IRI, that acts both at the local and remote organ level. The evaluation of VEGF and HIFs (under completion) will further clarify the underlying mechanisms. The study was supported by ESOT Grant.
2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1350749
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