AUTHOR=Piñeiro Gaston J. , Lazo-Rodriguez Marta , Ventura-Aguiar Pedro , Ramirez-Bajo Maria J. , Banon-Maneus Elisenda , Lozano Miquel , Cid Joan , Hierro-Garcia Natalia , Cucchiari David , Revuelta Ignacio , Montagud-Marrahi Enrique , Palou Eduard , Bayés-Genís Beatriu , Campistol Josep M. , Diekmann Fritz , Rovira Jordi 

TITLE=Extracorporeal Photopheresis Improves Graft Survival in a Full-Mismatch Rat Model of Kidney Transplantation

JOURNAL=Transplant International

VOLUME=Volume 36 - 2023

YEAR=2023

URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2023.10840

DOI=10.3389/ti.2023.10840

ISSN=1432-2277

ABSTRACT=<p>Extracorporeal photopheresis (ECP) is an immunomodulatory therapy based on the infusion of autologous cellular products exposed to ultraviolet light (UV) in the presence of a photosensitizer. The study evaluates the ECP efficacy as induction therapy in a full-mismatch kidney transplant rat model. Dark Agouti to Lewis (DA-L) kidney transplant model has been established. ECP product was obtained from Lewis rat recipients after DA kidney graft transplantation (Lew<sup>DA</sup>). Leukocytes of those Lew<sup>DA</sup> rats were exposed to 8-methoxy psoralen, and illuminated with UV-A. The ECP doses assessed were 10 × 10<sup>6</sup> and 100 × 10<sup>6</sup> cells/time point. Lewis recipients received seven ECP infusions. DA-L model was characterized by the appearance of donor-specific antibodies (DSA) and kidney function deterioration from day three after kidney transplant. The dysfunction progressed rapidly until graft loss (6.1 ± 0.5 days). Tacrolimus at 0.25 mg/kg prolonged rat survival until 11.4 ± 0.7 days (<italic>p</italic> = 0.0004). In this context, the application of leukocytes from LewDA sensitized rats accelerated the rejection (8.7 ± 0.45, <italic>p</italic> = 0.0012), whereas ECP product at high dose extended kidney graft survival until 26.3 ± 7.3 days, reducing class I and II DSA in surviving rats. ECP treatment increases kidney graft survival in full-mismatch rat model of acute rejection and is a suitable immunomodulatory therapy to be explored in kidney transplantation.</p>