The need for minimization strategies: current problems of immunosuppression.
New immunosuppressants and the better use of immunosuppressant combination therapy have led to significant improvements in renal allograft outcomes over the last decades. Yet, despite dramatic reduction in rejection rates and improvement in 1-year graft survival, long-term graft attrition rates remained rather constant. Current immunosuppressant combinations are frequently leading to overimmunosuppression and are increasing cardiovascular risk. Importantly, calcineurin inhibitors are nephrotoxic, contribute to cardiovascular risk and chronic allograft dysfunction. Furthermore, immunosuppressant-associated toxicities aggravate immune-mediated nephron injury and side effects lead to nonadherence, an identified important reason for late acute and chronic antibody-mediated rejections. The frequent development of a chronic humoral response indicates rather insufficient immunosuppression of current combinations than simple under-immunosuppression. While there is no evidence that increasing immunosuppressive doses will improve outcomes or reduce de novo HLA-antibody formation, there is clear evidence that adequate minimization strategies will reduce side effect burden. Because of low rejection risk, but frequent side effects, drug minimization is particularly relevant for the many maintenance patients. In summary, new therapeutic strategies need to be developed from adequately powered clinical trials for reduction of the many side effects of immunosuppressants. Such evidence-based and time-dependent immunosuppressive minimization strategies are needed to achieve better long-term outcomes in the future.
Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Jamal
J
Bamoulid
Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Oliver
O
Staeck
Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Fabian
F
Halleck
Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Dmytri
D
Khadzhynov
Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Susanne
S
Brakemeier
Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Michael
M
Dürr
Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Klemens
K
Budde
D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects* / Q000379:methods; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D016030:Kidney Transplantation; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology*; D028761:Withholding Treatment
D007166:Immunosuppressive Agents
immunosuppressants; kidney transplantation; long-term outcomes; minimization; side effects