Tailoring immunosuppressive therapy.

In the last decade, a paradigm shift has occurred in the field of renal transplantation. The use of new and powerful immunosuppressive drugs has led to excellent short-term patient and graft survival and very low acute rejection (AR) rates. Two burning questions have become paramount. The first is how can we improve long-term patient and graft survival despite the fact that more elderly patients are transplanted and that the growing demand for donor organs is more often counterbalanced by the use of marginal donors? The second question is how should we tailor the optimal immunosuppressive therapy to the individual patient profile? It is clear, for example, that a patient suffering from osteoporosis and diabetes mellitus will not benefit from the same immunosuppressive drug protocol as a patient who has severe arterial hypertension and hyperlipidaemia (Table 1). The older principle of ‘one fits all’ has become more and more obsolete. The first step in solving these questions is to examine which tools can be employed to objectively assess the individual efficacyutoxicity profile of specific drug regimens and to test the validity and reproducibility of these tools in clinical practice. The second step is to evaluate the presumed net beneficial effect of the progress made in immunosuppressive drug therapy in order to improve the efficacyutoxicity profile. In the last few years, very interesting and even controversial studies have been conducted in order to answer these questions. Steroid trials were the first attempt in that direction; reduced-dose calcineurin inhibitor (CNI)ulate introduction of CNI studies were soon to follow. At present, we are entering an era where CNI-free protocols are being put to the test and combinations that were initially considered impossible, such as mycophenolate mofetil (MMF)–rapamycin or tacrolimus–rapamycin, are under evaluation. Lastly, induction strategies using new monoclonal antibodies enable the use of minimal effective doses of concomitant immunosuppressive drugs. The challenge is to try and learn how patients might benefit in the long term from these new protocols rather than to focus on overall positive short-term results. As professionals involved in the daily care of patients living with a donor organ, we are experiencing exciting and provoking innovations. A brief and necessarily incomplete overview of recent studies trying to tackle these questions is presented here, focusing mainly on the results of randomized controlled trials.