A Paliege1, J Bamoulid1, F Bachmann1, O Staeck1, F Halleck1, D Khadzhynov1, S Brakemeier1, M Dürr1, K Budde2. 1. Medizinische Klinik mit Schwerpunkt Nephrologie, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 10117, Berlin, Deutschland. 2. Medizinische Klinik mit Schwerpunkt Nephrologie, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 10117, Berlin, Deutschland. klemens.budde@charite.de.
Abstract
BACKGROUND: Current immunosuppressive protocols effectively prevent acute rejection of renal allografts. Extensive drug toxicity and the deleterious effects of long-term immunosuppression are associated with significant morbidity and mortality. OBJECTIVES: The purpose of this article is to provide an overview over modern immunosuppressants and their unwanted side effects and to discuss strategies for improved long-term transplant survival. METHODS: Review of the current topic-related literature and discussion of our own experience. RESULTS: The use of antibody induction together with an initial combination therapy of calcineurin inhibitors, mycophenolate and steroids is recommended and results in excellent early outcomes. Detrimental effects include an increased incidence of infections, malignomas, and cardiovascular diseases. Long-term transplant survival is impaired by extensive drug toxicity and the frequent development of donor specific antibodies. Reduction of overall cumulative exposure to immunosuppressants or the reduction of specific toxic drugs such as calcineurin inhibitors and steroids may improve long-term results. Alternative immunosuppressants like mTOR inhibitors and belatacept appear to be effective and safe but their long-term effects on patient and allograft survival needs to be established in clinical trials. CONCLUSIONS: Current immunosuppressants provide effective protection from renal allograft rejection. However, their use is complicated by serious side effects. In the future, development of novel immunosuppressants and optimization of minimization strategies may help to improve long-term success after kidney transplantation.
BACKGROUND: Current immunosuppressive protocols effectively prevent acute rejection of renal allografts. Extensive drug toxicity and the deleterious effects of long-term immunosuppression are associated with significant morbidity and mortality. OBJECTIVES: The purpose of this article is to provide an overview over modern immunosuppressants and their unwanted side effects and to discuss strategies for improved long-term transplant survival. METHODS: Review of the current topic-related literature and discussion of our own experience. RESULTS: The use of antibody induction together with an initial combination therapy of calcineurin inhibitors, mycophenolate and steroids is recommended and results in excellent early outcomes. Detrimental effects include an increased incidence of infections, malignomas, and cardiovascular diseases. Long-term transplant survival is impaired by extensive drug toxicity and the frequent development of donor specific antibodies. Reduction of overall cumulative exposure to immunosuppressants or the reduction of specific toxic drugs such as calcineurin inhibitors and steroids may improve long-term results. Alternative immunosuppressants like mTOR inhibitors and belatacept appear to be effective and safe but their long-term effects on patient and allograft survival needs to be established in clinical trials. CONCLUSIONS: Current immunosuppressants provide effective protection from renal allograft rejection. However, their use is complicated by serious side effects. In the future, development of novel immunosuppressants and optimization of minimization strategies may help to improve long-term success after kidney transplantation.
Authors: Brian J Nankivell; Richard J Borrows; Caroline L-S Fung; Philip J O'Connell; Richard D M Allen; Jeremy R Chapman Journal: N Engl J Med Date: 2003-12-11 Impact factor: 91.245
Authors: Teun van Gelder; Helio Tedesco Silva; Johan W de Fijter; Klemens Budde; Dirk Kuypers; Gunnar Tyden; Aleksander Lohmus; Claudia Sommerer; Anders Hartmann; Yann Le Meur; Michael Oellerich; David W Holt; Burkhard Tönshoff; Paul Keown; Scott Campbell; Richard D Mamelok Journal: Transplantation Date: 2008-10-27 Impact factor: 4.939