Outcome After Steroid Withdrawal in Renal Transplant Patients Receiving Tacrolimus-Based Immunosuppression (original) (raw)
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Transplantation Proceedings, 2005
Steroid-induced adverse effects after transplantation include cosmetic, metabolic, and cardiovascular complications. Steroid withdrawal or avoidance with cyclosporine-based regimens have been hampered by an unacceptably high rate of acute rejections and increased rates of graft loss. Recently the results of several large, randomized trials of steroid withdrawal/avoidance with tacrolimus-based immunosuppression in renal transplant recipients became available. A review of these trials appeared to be of clinical interest. Data from the THOMAS trial clearly indicate that steroid withdrawal from a regimen of tacrolimus, mycophenolate mofetil (MMF), steroids after 3 months after transplantation is safe with regard to acute rejection rate and graft survival. If an induction therapy with daclizumab is used in combination with tacrolimus and MMF (CARMEN trial), even steroid avoidance is safe with regard to acute rejection rate and graft survival. Finally, in the ATLAS trial, steroid avoidance with basiliximab in combination with tacrolimus (resulting in tacrolimus monotherapy) or alternatively with tacrolimus and MMF both resulted in similar graft survival, but higher rates of acute rejection. In conclusion, steroid withdrawal is safe from a triple-drug regimen of tacrolimus, MMF, and steroids after 3 months after transplantation, and steroid use may completely be avoided with tacrolimus, and MMF combined with daclizumab induction. Tacrolimus monotherapy may be achieved using basiliximab induction at the price of higher rates of acute rejection, but with unaffected graft survival. Thus tacrolimus-based immunosuppression with or without interleukin-2 receptor antagonist induction has made steroid withdrawal or avoidance a realistic option in renal transplantation.
Transplantation, 2000
Background-Corticosteroids have always been an integral part of immunosuppressive regimens in renal transplantation. The primary goal of this analysis was to assess the safety of steroid withdrawal in our pediatric renal transplant recipients receiving tacrolimus-based immunosuppression. December 1989 and December 1996, 82 renal transplantations were performed in pediatric patients receiving tacrolimus-based immunosuppression. Two of these patients lost their grafts within 3 weeks of transplantation (and were still on steroids at the time of graft loss), and were excluded from further analysis. Seventy-four patients (92.5%) were taken off prednisone a median of 5.7 months after transplantation. Of these 74, 56 (70%) remained off prednisone (OFF), and 18 (22.5%) were restarted on prednisone a median of 14.8 months after discontinuing steroids (OFF → ON). 6(7.5%) were never taken-off prednisone (ON). The mean follow-up was 59±23 months.
Transplantation, 1999
Background-Corticosteroids have always been an integral part of immunosuppressive regimens in renal transplantation. The primary goal of this analysis was to assess the safety of steroid withdrawal in our pediatric renal transplant recipients receiving tacrolimus-based immunosuppression. December 1989 and December 1996, 82 renal transplantations were performed in pediatric patients receiving tacrolimus-based immunosuppression. Two of these patients lost their grafts within 3 weeks of transplantation (and were still on steroids at the time of graft loss), and were excluded from further analysis. Seventy-four patients (92.5%) were taken off prednisone a median of 5.7 months after transplantation. Of these 74, 56 (70%) remained off prednisone (OFF), and 18 (22.5%) were restarted on prednisone a median of 14.8 months after discontinuing steroids (OFF → ON). 6(7.5%) were never taken-off prednisone (ON). The mean follow-up was 59±23 months.
Annals of transplantation : quarterly of the Polish Transplantation Society, 2002
This prospective, randomized, multicentre study investigated the efficacy and safety of two tacrolimus-based regimens and their potential to withdraw steroids. In total 489 patients were randomised to receive either tacrolimus and MMF (n = 243) or tacrolimus and azathioprine (n = 246) concomitantly with steroids in both treatment groups. The initial oral dose of tacrolimus was 0.2 mg/kg/day, MMF dose was 1 g/day, azathioprine was administered at 1-2 mg/day. Steroids were tapered from 20 mg/day to 5 mg/day. From month 3 onwards, steroids were withdrawn in patients who were free from steroid-resistant rejection and who had serum creatinine concentrations < 160 mumol/L. Study duration was 6 months. Patient survival at month 6 was 98.3% (Tac/MMF/S) and 98.4% (Tac/Aza/S), graft survival at 6 month was 95.0% (Tac/MMF/S) and 93.5% (Tac/Aza/S). The 6-month incidences of biopsy-proven acute rejection were 18.9% (Tac/MMF/S) compared with 26.8% (Tac/Aza/S), p = 0.038. The 6-month incidences...
Transplantation direct, 2018
The optimal immunosuppressive regimen in kidney transplant recipients, delivering maximum efficacy with minimal toxicity, is unknown. The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in 305 kidney transplant recipients, in which 2 immunosuppression minimization strategies-one consisting of early steroid withdrawal, the other of tacrolimus minimization 6 months after transplantation-were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. The primary endpoint was kidney function. Secondary endpoints included death, primary nonfunction, graft failure, rejection, discontinuation of study medication, and a combined endpoint of treatment failure. An interim analysis was scheduled at 6 months, that is, just before tacrolimus minimization. This interim analysis revealed no significant differences in Modification of Diet in Renal Disease between the early ster...
Withdrawal of steroids from triple‐drug therapy in kidney transplant patients
Nephrology Dialysis …, 2000
Introduction Background. In renal transplant patients with stable graft function, triple-drug immunosuppression may Triple-drug therapy is the most widely used regimen not be necessary, while withdrawal of steroids may in kidney transplantation [1], but no benefit of its eliminate side effects. The primary aim of this study long-term use has been demonstrated, and it may be was to assess the risk of rejection after steroid unnecessary in most patients. Because of their side withdrawal. effects, steroids are the first candidate to be removed Methods. A total of 88 patients with stable graft from the immunosuppressive regimen. Steroid-free function and serum creatinine <160 mmol/l, treated therapy would be beneficial for particular groups of with cyclosporin A, azathioprine and prednisone were patients such as children [2], elderly [3], diabetics [4], randomized into group A (n=46) with a gradual patients with osteoporosis [5] and hyperlipidaemia [6 ]. prednisone reduction to zero in the course of 6 months, The main risk associated with steroid withdrawal is and group B (n=42) on triple-drug therapy without rejection [7]. One of the important factors is the timing change. At the time of randomization, fine-needle of steroid withdrawal [7]. aspiration biopsy (FNAB) was carried out in all of The aim of this project was to assess the risk for the patients. After stopping steroids, the patients were rejection in a controlled study where steroids were followed up for a period of 12 months. withdrawn 1 year after transplantation, employing Results. Four patients failed to complete steroid withfine-needle aspiration biopsy (FNAB) as a possible drawal, three due to rejection, and one due to leukopredictor of rejection. penia. The proportion of rejection in three patients in group A (6.6%) was not significantly different from rejection in two patients in group B (4.8%). The mean Subjects and methods value of serum creatinine was not significantly different in both groups in the course of follow-up. A finding Eighty-eight patients after their first kidney transplantation, of some degree of immunological activity in FNAB with stabilized graft function, and serum creatinine under was made in four patients in each group, but none of 160 mmol/l, treated with cyclosporine A, azathioprine and these patients developed rejection. Compared with prednisone were randomized, according to the month of group B, significant decreases in serum cholesterol and birth, into a withdrawal group (A, n=46), and a control blood leukocytes were observed in group A. Prednisone group (B, n=42). Only one graft for the patient in group B was from living donor, 87 grafts were from cadaverous withdrawal did not have any influence on hypertension donors. There was no statistical difference in the main and serum triglycerides. characteristic features (Table 1) between both groups. Conclusions. Gradual withdrawal of steroids is not In patients of group A, prednisone was gradually withassociated with a higher risk for rejection and has a drawn over a period of 6 months, while the dose of cyclospobeneficial effect on serum total cholesterol levels. rin A was adjusted to keep whole blood levels in the upper FNAB was not a useful tool for predicting rejection. half of the therapeutic range, and azathioprine dose on a minimum of 1.5 mg/kg/day. The immunosuppressive proto-Keywords: fine-needle aspiration biopsy; immunocol in patients of group B was not changed. Duration of suppressive treatment; kidney transplantation; follow-up after stopping steroids was 12 months. rejection; steroid withdrawal; triple-drug therapy Rejection was suspected, when serum creatinine increased more than 30 mmol/l. All rejections were confirmed by biopsy assessed according to Banff classification. FNAB was carried out in a modification after Häyry and
Effect of long-term steroid withdrawal in renal transplant recipients: a retrospective cohort study
NDT plus, 2010
Background. Steroids are largely effective for the immunosuppressive treatment in renal transplant patients, but cause severe side effects. Whether steroid withdrawal confers long-term beneficial effects remains unclear.Methods. Data on 4481 cadaveric kidney transplant recipients were collected to estimate the impact of steroid withdrawal on kidney function and graft and patient survival using multivariate Cox regression models.Results. A total of 923 patients (20.6%) had steroid treatment withdrawn. This was more common in recipients from younger donors and in older recipients, and in recipients with a first transplant, those who had pre-transplant or de novo diabetes mellitus and those with fewer episodes of acute rejection (AR) (22.4% vs. 29.2%, P < 0.001). Cox multivariate analysis stratifying by propensity scores showed that long-term steroid therapy was associated with a 70% increase in the risk of patient death. The repeated measures linear model showed that, although the ...