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=36 YEAR=2023 URL=https://www.frontierspartnerships.org/articles/10.3389/ti.2023.10840 DOI=10.3389/ti.2023.10840 ISSN=1432-2277 ABSTRACT=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 (LewDA). Leukocytes of those LewDA rats were exposed to 8-methoxy psoralen, and illuminated with UV-A. The ECP doses assessed were 10 × 106 and 100 × 106 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 (p = 0.0004). In this context, the application of leukocytes from LewDA sensitized rats accelerated the rejection (8.7 ± 0.45, p = 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.