Even though current immunosuppressive drugs are very potent, acute kidney rejection episodes (incidence around 7%) still occur, and few of them are refractory to conventional therapeutic schemes: high-dose steroids, polyclonal or monoclonal antibodies. In these cases, further treatment is usually considered too dangerous for the patient if it is taken into account the poor prognosis for the renal graft1.
Extracorporeal photoapheresis (ECP) is a form of apheresis-based immunomodulatory therapy that was introduced by Edelson in the 1980s. Despite it has been approved by the FDA for treating cutaneous T-cell lymphoma, it has an expanding array of indications including graft-versus-host disease (acute or chronic), rheumatic diseases, pemphigus vulgaris, and acute allograft rejection treatment in cardiac, lung, liver, and kidney transplant1-4.
During ECP mononuclear leucocytes are separated from whole blood using centrifugation. A photosensitizing agent (8 metoxipsoralen) is added and the white cells are then irradiated with ultraviolet light A before being returned to the patient. Only are treated 10-20% of the patient white cells during the procedure1,2.
The key mechanism of this ECP is induction of leukocyte apoptosis. After reinfusion to the patient, the apoptotic white cells are engulfed by antigen-presenting cells triggering a T citotoxic induced autoimmunity effect against T pathologic lymphocytes, what have been called "auto-vaccination theory", and a T cell regulatory effect that induce tolerance to pathologic cells, contributing in this case to the receptor graft tolerance1,5-6.
ECP has the following advantages: it is nontoxic, well tolerated, with no general immunosuppressive actions, and consequently not intrinsic risk for developing infective events and /or malignancies. The main described potential, but uncommon, ECP-related side effects are: transient hypotension, febricula, chills, headache, and/or anemia secondary to a clotty kit or a problem with blood reinfusion 2,3,7.
Even though, there are few report regarding using ECP as adjuvant treatment for handling refractory acute kidney rejection, all of them has described it as an effective and safe therapy, thus it should be taken into account for rescuing graft at risk in these transplant clinical settings.
1.-Genberg H, Kumlien G, Shanwell A, Tydén G. Refractory acute renal allograft rejection successfully treated with photopheresis. Transplant Proc. 2005;37(8):3288-3289.
2.- Kusztal M, Koscielska-Kasprzak K, Gdowska W, Zabinska M, Myszka M, Klak R, Krajewska M, Boratynska M, Szyber P, Chudoba P, Patrzalek D, Klinger M. Extracorporeal photopheresis as an antirejection prophylaxis in kidney transplant recipients: preliminary results.Transplant Proc. 2011;43(8):2938-2940.
3.- Edelson RL. Extracorporeal Photopheresis. Photodermatol. 1984; 5:209-210.
4.- Edelson R. Treatment of cutaneous T-Cell Lymphoma by extracorporeal photochemotherapy. N Engl J Med. 1987; 316: 297-303.
5.- Kusztal M, Klak R, Krajewska M, Boratynska M, Patrzalek D, Klinger M. Application of extracorporeal photopheresis in kidney transplant recipients: technical considerations and procedure tolerance. Kusztal M, Klak R, Krajewska M, Boratynska M, Patrzalek D, Klinger M.Transplant Proc. 2011;43(8):2941-2942.
6.- Russo GE, D'Angelo AR, Testorio M, Mazza F, Borzacca B, Cicchinelli A, Laudani G, Serriello I, Casarci M, Guido A, Cavallini M. New therapeutic prospects for renal transplant: extracorporeal photochemotherapy].G Ital Nefrol. 2012;29 Suppl 54:S36-39.
7.- Lai Q, Pretagostini R, Gozzer M, Cinti P, Meo D, Vita F, Bafti MS, Poli L, Novelli G, Rossi M, Girelli G, Berloco PB. [Multimodal treatment for acute antibody-mediated renal transplant rejection: successful rescue therapy with combined plasmapheresis, photopheresis and intravenous immunoglobulin]. G Ital Nefrol. 2012; 29 Suppl 54:S31-35.
Carlos G. Musso
Servicio de Nefrología.
Hospital Italiano de Buenos Aires
Mail: carlosmusso @ gmail.com