Pharmacogenetics and immunosuppressive drugs in solid organ transplantation

2014 ◽  
Vol 10 (12) ◽  
pp. 725-731 ◽  
Author(s):  
Teun van Gelder ◽  
Ron H. van Schaik ◽  
Dennis A. Hesselink
2016 ◽  
Vol 38 ◽  
pp. S1-S20 ◽  
Author(s):  
Mercè Brunet ◽  
Maria Shipkova ◽  
Teun van Gelder ◽  
Eberhard Wieland ◽  
Claudia Sommerer ◽  
...  

2018 ◽  
Vol 13 (11) ◽  
pp. 1760-1764 ◽  
Author(s):  
Paloma Leticia Martin-Moreno ◽  
Sudipta Tripathi ◽  
Anil Chandraker

The ability of the immune system to differentiate self from nonself is critical in determining the immune response to antigens expressed on transplanted tissue. Even with conventional immunosuppression, acceptance of the allograft is an active process often determined by the presence of regulatory T cells (Tregs). Tregs classically are CD4+ cells that constitutively express high levels of the IL-2 receptor α chain CD25, along with the transcription factor Foxp3. The use of Tregs in the field of solid organ transplantation is related specifically to the objective of achieving tolerance, with the goal of reducing or eliminating immunosuppressive drugs as well as maintaining tissue repair and managing acute rejection. A key issue in clinical use of Tregs is how to effectively expand the number of Tregs, either through increasing numbers of endogenous Tregs or by the direct infusion of exogenously expanded Tregs. In order to realize the benefits of Treg therapy in solid organ transplantation, a number of outstanding challenges need to be overcome, including assuring an effective expansion of Tregs, improving long-term Treg stability and reduction of risk-related to off-target, nonspecific, immunosuppressive effects related specially to cancer.


2012 ◽  
Vol 153 (34) ◽  
pp. 1341-1349
Author(s):  
Ádám Remport ◽  
Dávid Dankó ◽  
Zsuzsa Gerlei ◽  
Krisztina Czebe ◽  
István Kiss

Long-term success in solid organ transplantation strongly depends on the optimal use of maintenance immunosuppressive treatment. Cyclosporin and tacrolimus are the most frequently administered immunosuppressants and they are designed to narrow therapeutic index drugs. The substitution of the branded formulation by their generic counterparts may lead to economic benefit only if equivalent clinical outcomes can be achieved. There is no published evidence to date on the guarantee of their long-term therapeutic equivalence and cases of therapeutic failures have been reported due to inadvertent drug conversion. The disadvantageous clinical consequences of a non medical, mechanistic forced switch from the original to generic formulation of tacrolimus and the estimated loss of the payer’s presumed savings are presented in a kidney transplant recipient population. Special problems related to pediatric patients, drug interactions with concurrent medications and the burden of additional therapeutic drug monitoring and follow up visits are also discussed. The authors are convinced that the implementation of the European Society of Organ Transplantation guidelines on generic substitution may provide a safe way for patients and healthcare payers. Orv. Hetil., 2012, 153, 1341–1349.


2012 ◽  
Vol 153 (33) ◽  
pp. 1294-1301
Author(s):  
Balázs Pőcze ◽  
Péter Németh ◽  
Róbert Langer

Solid organ transplantation has shown improvement in patient and graft survival rates due to the development of immunosuppression in the last fifty years; however only the last two decades led to the development of new, baseline immunosuppressive drugs that avoid the unlikely side effects of calcineurin inhibitors, especially nephrotoxicity. The transplanted organ is foreign to the host and, therefore, it induces a complex immune response of the recipient. In this review, a brief outline of immune response is given, followed by the introduction of new immunosuppressive drugs acting via variant pathways. These are compounds which are already in use or becoming shortly available and are potential future alternatives for the calcineurin inhibitors. This paper highlights the role of co-stimulation blockade with belatacept and the recently even more intensively studied field of tolerance induction. Orv. Hetil., 2012, 153, 1294–1301.


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