Immunosuppression in renal transplantation: some aspects for the modern era.
New classes of agents have sequentially increased the specificity of post-transplant immunosuppression, leading to profound improvements in success rates after renal transplantation. The next era will focus on increased long-term survival rates through optimal use of existing agents and the rational development of drugs based on prior identification of specific immunologic targets. Conventionally, long-term outcomes after kidney transplantation have been assessed by surrogate markers, notably acute rejection, but graft-threatening complications such as development of new-onset diabetes mellitus and polyomavirus nephropathy must be addressed if long-term survival rates are to be improved. Mycophenolic acid therapy must be administered optimally to ensure that adequate exposure is achieved in the immediate post-transplant period and, subsequently, by avoiding underdosing due to gastrointestinal events. Chronic allograft nephropathy remains a major concern, and protocol-led, reliable monitoring strategies are essential to enable early intervention, for example, through introduction of proliferation signal inhibitor therapy with concomitant calcineurin inhibitor reduction or withdrawal. The range of immunosuppressive regimens now available and in development, together with improved assessment of patients' risk profiles for immunologic events and comorbid disease, offers the opportunity for further individualization of immunosuppression after renal transplantation.
Chadban
Steven
S
Royal Prince Alfred Hospital, University of Sydney, Camperdown, NSW 2050, Australia. steve.chadban@cs.nsw.gov.au
Morris
Randall
R
Hirsch
Hans H
HH
Bunnapradist
Suphamai
S
Arns
Wolfgang
W
Budde
Klemens
K
D015415:Biomarkers; D065095:Calcineurin Inhibitors; D003920:Diabetes Mellitus; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D027601:Polyomavirus Infections; D015996:Survival Rate
D015415:Biomarkers; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid