Steroid withdrawal in renal transplant recipients

Abstract

STEROID withdrawal is one of the most controversial issues in renal transplantation. Corticosteroids are closely associated with several risk factors: hypertension, diabetes, hyperlipidemia, etc (Table 1). Nevertheless, the majority of transplant teams prefer to maintain low steroid doses to prevent chronic rejection. There are several factors that can influence the success or failure of steroid withdrawal: patient selection criteria, posttransplant interval, timing of withdrawal, concomitant immunosuppression, adequate cyclosporine (CsA) blood levels, etc. One interesting question is whether steroids can be totally avoided using CsA (or tacrolimus) as the sole induction immunosuppression therapy. There is actually substantial information in the literature showing that, despite the high rate of acute rejection, long-term graft survival rates are excellent and more than 50% of the patients can be maintained free of steroids. Another question is whether steroid withdrawal early rather than late after transplantation results in a higher rate of acute rejection. It is generally accepted that if steroids are gradually reduced, starting after 6 months posttransplantation, the risk of acute rejection remains very low. However, the new immunosuppressive drugs currently employed, like mycophenolate mofetil (MMF) or tacrolimus, offer excellent opportunities to try new strategies of steroid withdrawal. For example, excellent results have been obtained using tacrolimus in combination with MMF despite cessation of corticosteroid therapy one week after transplantation. Some clinical trials have examined the correlation between corticosteroid therapy cessation and the development of chronic graft nephropathy. A prospective randomized study performed by the Canadian Multicentre Study Group which included a large number of patients showed that patients in the withdrawal group were at a higher risk of acute rejection and had a lower graft survival rate than patients maintained on steroids. However, the data collected by Opelz in the Collaborative Transplant Study, with a very large number of patients (minimizing the risk of a positive bias in the selection), showed that patients receiving maintenance immunosuppressive therapy with CsA without steroids have the best long-term patient and graft survival rates. Our own experience is based on a retrospective study of 102 patients who were withdrawn from steroids 58 6 35 months after transplantation (Table 2). They presented a postwithdrawal acute rejection rate of 14.7%, which occurred between 1.8 and 63 months after steroid withdrawal (mean 13 6 13 months). Two patients in the rejection group lost their graft due to rejection. Currently 80 patients (78%) remain steroid free. Finally, the results of a double-blind, multi-center study comparing two corticosteroid regimens plus MMF and CsA for prevention of acute renal allograft rejection are presented. This study was prospectively conducted in 500 renal transplant patients who received CsA and MMF in combination with either standard steroid therapy (control group) or with low doses of steroids and total withdrawal after 3