Steroid- and calcineurin inhibitor free immunosuppression in kidney transplantation: state of the art and future developments.
Owing to the increasing disparity of organ demand and organ supply the search for optimal immunosuppressive strategies has become a central issue in kidney transplantation (KTX). In the focus today are modifications of the use of calcineurin-inhibitors (CNIs, Cyclosporine A/Tacrolimus) and steroids, as they are nephrotoxic and promote cardiovascular risk factors like arterial hypertension, hyperlipidemia and diabetes mellitus. These modifications can either be withdrawal or avoidance of these substances in combination with new and/or established immunosuppressants. Because about half of all KTXs are performed by or with the help of urologists' knowledge of modern immunosuppressive regimens is crucial also for urologists. We performed a literature research (PubMed, DIMDI, medline) for CNI- and steroid-sparing protocols and studies to elucidate their influence on graft-function and graft- and patient-survival. New substances and actual studies were also evaluated. Several published reports on CNI- and steroid-sparing protocols after KTX exist, including withdrawal, reduction or avoidance. The time of reduction seems to be crucial: an initially increased immune response should be counterbalanced by an initially intensified immunosuppression. Therefore, late steroid withdrawal seems to be safer than early withdrawal especially in Cyclosporine-based immunosuppression. Steroid avoidance also seems feasible on a CNI based regimen, especially in context with induction therapy. Withdrawal or avoidance of CNIs seems feasible with mycophenolate acid and/or induction therapy with IL 2-receptor antibodies as co-immunosuppressants. This is of interest in grafts with deteriorating function or from donors with extended criteria. Also, CNI- and steroid-free immunosuppression can be successfully performed with new immunosuppressants but results are yet premature. CNI- and/or steroid reduction, withdrawal or even avoidance is feasible. As long-term graft function is the goal of KTX and as more kidneys from donors with extended criteria are transplanted "tailored immunosuppression" will replace standards in the future.
Giessing
Markus
M
Department of Urology, Campus Mitte, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany. markus.giessing@charite.de
Fuller
Tom Florian
TF
Tuellmann
Max
M
Slowinski
Torsten
T
Budde
Klemens
K
Liefeldt
Lutz
L
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D002318:Cardiovascular Diseases / Q000139:chemically induced; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000139:chemically induced; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D065095:Calcineurin Inhibitors; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2