Humar et al74reported on 149 recipients who had 1 ARE while on our RDP protocol

Humar et al74reported on 149 recipients who had 1 ARE while on our RDP protocol. have been associated with increased late rejection risk. Isoconazole nitrate A more exciting innovation has been the attempts at rapid discontinuation (7 days posttransplantation) of prednisone with the following results: (1) Randomized studies have shown no significantly increased risk of acute rejection; (2) Randomized and nonrandomized studies have shown no increase in late graft loss; (3) Successful use in living and deceased donor recipients, primary and retransplant recipients, adult and child recipients, white and black recipients, and low-risk and highly sensitized recipients; (4) About 80% of recipients remain prednisone-free long term. Recent nonrandomized data suggest that recipients who have an acute rejection episode while prednisone free are more likely to have a second rejection episode if they are returned to prednisone-free immunosuppression. In these cases the acute rejection episode should be treated and long-term prednisone continued at 5 mg/d. The goal of steroid minimization protocols has been to eliminate or minimize steroid-related side Isoconazole nitrate effects while not increasing the rates of acute rejection episodes (ARE) or chronic graft loss. Until recently, corticosteroids had been a mainstay of Mouse monoclonal to CK1 immunosuppressive protocols in kidney transplantation. However, although inexpensive, steroids are associated with debilitating side effects, including hypertension, hyperlipidemia, cataracts, avascular necrosis, osteoporosis, mood and appearance changes, and, in children, growth retardation.1Vanrenterghem et Isoconazole nitrate al2recently showed that increased long-term total steroid dose is associated with increased cardiovascular morbidity. Treatment of these steroid-related side effects adds to the cost of transplants.3In addition, such side effects increase posttransplant noncompliance4; noncompliance is Isoconazole nitrate usually associated with an increased incidence of ARE, chronic rejection, and graft loss.5Thus, a hidden cost of steroid-related side effects may be increased graft loss. When surveyed, kidney transplant recipients state that the immunosuppressive drug they would most like not to take is usually prednisone.6 == LATE (3 MONTH) STEROID WITHDRAWAL == Historically, numerous attempts have been Isoconazole nitrate made either to avoid steroids or, in selected recipients, to gradually withdraw steroids late (3 months) posttransplantation. However, meta-analyses of studies of late steroid withdrawal in selected recipients on calcineurin inhibitors and either azathioprine (AZA) or mycophenolate mofetil (MMF) showed an increased incidence of ARE and graft loss.79 Of particular concern has been a multicenter Canadian study in which recipients on cyclosporine (CsA) and prednisone were randomized at 3 months to either switch to CsA monotherapy or to continue the 2 2 drugs.10For the first 500600 days after randomization, the studys authors found no significant differences between the 2 groups; however, thereafter the CsA monotherapy group had an increased rate of graft loss. The Canadian study has led to ongoing concerns that even if steroid minimization protocols have early success, late graft failure will significantly increase. Yet it is critical to realize that this study was done before the impact of ARE on long-term graft outcome was recognized11,12; the authors did not determine whether the rate of ARE increased after prednisone withdrawal. In contrast with these studies, Opelz et al13recently reported no increased ARE rates for recipients on CsA-based immunosuppression who underwent steroid withdrawal >6 months posttransplantation. Median time to steroid withdrawal was 1.1 years; after enrollment, steroids were tapered in a stepwise fashion. Using the Collaborative Transplant Study (CTS) database, Opelz et al matched each enrolled recipient (n= 1015) with 3 controls. The actuarial 7-year patient, graft, and death-censored graft survival rates were significantly better for the withdrawal group (P< .01). Outcomes did not differ for those treated with AZA or MMF. The difference in outcomes between Opelzs and the above studies may be due to the later withdrawal of steroids in Opelzs study. Although many of the early reports of late prednisone withdrawal included recipients treated with a calcineurin inhibitor plus AZA or MMF, success has also been recently reported with mammalian target of rapamycin (mTOR) inhibitors.1418 == RAPID DISCONTINUATION OF PREDNISONE == The recognition that late steroid withdrawal was associated with.