Journal Information
Vol. 36. Issue. 3.May - June 2016
Pages e1-e52Pages 217-332
Vol. 36. Issue. 3.May - June 2016
Pages e1-e52Pages 217-332
Letter to the Editor
DOI: 10.1016/j.nefroe.2015.06.013
Open Access
Role of photopheresis in the treatment of refractory cellular rejection in kidney transplantation
Papel de la fotoaféresis en el tratamiento del rechazo celular agudo refractario en trasplante renal
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Ernesto José Fernándeza, Celia Lópeza,
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Celia.loap@gmail.com

Corresponding author.
, Ana Ramíreza, Rita Guerraa, Lucía Lópeza, Fernando Fernándezb, Manuel Tapiab, César García-Cantóna
a Unidad de Trasplante Renal, Servicio de Nefrología, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Las Palmas, Spain
b Servicio de Hematología y Hemoterapia, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Las Palmas, Spain
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To the Editor,

Extracorporeal photopheresis is an immunomodulatory technique based on the apoptotic effects of 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) light on leukocytes. It is widely used in T-cell-mediated diseases such as cutaneous T-cell lymphoma, graft vs host disease, rheumatoid arthritis, and systemic lupus erythematosus.1 Its use as prophylaxis for acute rejection (AR) in lung and heart transplants seems promising. However, there are few published articles on its use in the treatment of acute cellular rejection refractory to conventional treatment in renal transplant patients.

We present the case of a 56-year-old man, who received a cadaveric donor renal transplant in May 2013. Induction immunosuppression was with basiliximab, tacrolimus, mycophenolate mofetil, and steroids. Renal function was immediate and maintained until 16 days post-transplant, when it deteriorated. Percutaneous renal biopsy was performed, demonstrating Banff type Ib acute cellular rejection. Anti-HLA, anti-MICA, and antiendothelial antibodies were negative. The patient received salvage therapy with methylprednisolone (3×500mg) and thymoglobulin (1.25mg/kg; total cumulative dose, 410mg) without improvement. Seventeen days later a second renal biopsy was performed, reported as Banff type IIa acute cellular rejection, with mild intimal arteritis. Given the clinical course and refractoriness to treatment, with serum creatinine (SCr) of 2.97mg/dL, photopheresis was prescribed (14 sessions, once per week, with Therakos® UVAR XTS® System) along with nonspecific human gammaglobulin (200mg/kg; total dose, 80g). Following this, a progressive improvement was seen in renal function, with SCr of 2.3mg/dL on discharge. Renal function remained stable for 9 months, then deteriorated slightly, with a SCr of 2.62mg/dL, so it was decided to start a new course of photopheresis (6 sessions, once weekly). There was a good response to treatment (7 months later, the current SCr of 1.9mg/dL) and no treatment-related infectious complications were noted.

Prophylactic treatment with photopheresis in renal transplant patients in addition to standard immunosuppression has shown improvement in renal function at 6 months and an increase in regulatory T-cells (Tregs).2 Regarding its use in refractory AR, data from the literature are scarce, and, at times, contradictory. Horina et al. describe 3 patients treated with monthly photopheresis, who had no improvement in renal function, re-starting dialysis after a few months.3 However, in other publications, more frequent schedules have been associated with improvement of renal function.4 Dall’Amico et al. describe 4 patients with different types of cellular rejection, who had previously received OKT3, with improvement in renal function after the first cycle of photopheresis treatment. Renal function remained stable one year later, allowing a reduction in immunosuppressive therapy.5 Weekly, fortnightly, and monthly schedules were used, up to a total of 19 sessions.

The different mechanisms by which photopheresis exerts its beneficial effects are not completely understood. It seems to be related to triggering an immunomodulatory response of alloreactive T cells exposed to 8-MOP and to UVA light. It is likely that important roles are played by the synthesis of interleukins (especially TNF, IL-10, and IL-6) and the increase in regulatory T-cells (CD4+, CD25+ and FoxP3+), which increase progressively in number after each session. These mechanisms could explain why the benefits in cutaneous T-cell lymphoma are seen from the second or third month, while in AR they can be seen after a few days.

Currently, photopheresis could be useful as salvage therapy in cases of acute cellular rejection refractory to conventional treatment in renal transplants. More extensive investigation is needed to test its efficacy and safety.

Conflicts of interest

The authors declare no conflicts of interest.

References
[1]
J. Adamski, T. Kinard, T. Ipe, L. Cooling.
Extracorporeal photopheresis for the treatment of autoinmune diseases.
Transfus Apher Sci, 52 (2015), pp. 171-182
[2]
M. Kusztal, K. Koscielska-Kasprzak, W. Gdowska, M. Zabinska, M. Myszka, R. Klak, et al.
Extracorporeal photopheresis as an antirejection prophylaxis in kidney transplant recipients: preliminary results.
Transplant Proc, 43 (2011), pp. 2938-2940
[3]
J.H. Horina, R.R. Mullegger, S. Horn, H. Holzer, G. Halwachs, H. Kerl, et al.
Photopheresis for renal allograft rejection.
Lancet, 346 (1995), pp. 61
[4]
J.T. Wolfe, J.E. Tomaszewski, R.A. Grossman, S.L. Gottlieb, A. Naji, K.L. Brayman, et al.
Reversal of acute renal allograft rejection by extracorporeal photopheresis: a case presentation and review of the literature.
[5]
R. Dall’Amico, L. Murer, G. Montini, B. Andreetta, G. Franco-Zanon, G. Zacchello, et al.
Succesful treatment of recurrent rejection in renal transplant patients with photopheresis.
J Am Soc Nephrol, 9 (1998), pp. 121-127

Please cite this article as: Fernández EJ, López C, Ramírez A, Guerra R, López L, Fernández F, et al. Papel de la fotoaféresis en el tratamiento del rechazo celular agudo refractario en trasplante renal. Nefrologia. 2016;36:327–328.

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