*Purpose: Extracorporeal photopheresis (ECP) is an immunomodulatory cell therapy based on the infusion of autologous cellular products exposed to ultraviolet light (UV), in the presence of a photosensitizer. Nowadays, the three main indications for ECP therapy are cutaneous T-cell lymphoma, graft-versus-host disease and pulmonary or heart transplant rejection. The aim of the present study is to evaluate ECP therapy for the prevention of rejection in full mismatch kidney transplant rat model.

*Methods: We have established the Dark Agouti to Lewis (DA-LEW) full-mismatch kidney transplant model. Calcineurin inhibitor, tacrolimus, was administered at different doses for 4 days. ECP product was obtained from LEW recipients at day 4 after DA kidney graft transplantation. Peripheral blood and spleen of those LEW rats were processed until cell suspension, which was exposed to 8-methoxypsoralen (300 ng/mL) and illuminated with UV-A light (2 J/cm²). Seven doses of ECP were administered to LEW recipients, the first doses at day 14 before transplantation, and the last one at day 14 after transplantation.

*Results: DA-LEW kidney transplant model was characterized by renal function deterioration from day 3 and progressed rapidly until graft loss and rat death, with a mean survival time (MST) of 6.125±0.45 days. Donor specific antibodies were detected from day 3. Kidney graft histological analysis showed cortical necrosis, peritubular capillaritis, thrombotic microangiopathy, interstitial infiltrated, mainly by polymorphonuclear leukocytes and macrophages, and C4d deposition on peritubular capillaries. Short treatment with Tacrolimus (0.25mg/kg) prolonged rat survival until 11.4±0.70 days (P=0.0004). The combination of Tacrolimus and ECP therapy extended kidney graft survival until 26.28±7.3 days (P=0.0470).

*Conclusions: ECP is a suitable immunomodulatory therapy to be explored in the field of kidney transplantation.

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