INTRODUCTION — The utility of glucocorticoids (also called corticosteroids or steroids) in transplantation was first discovered in the 1950s with experiments demonstrating the ability of these agents to enhance survival of rabbit skin grafts [1]. These observations led to the clinical use of glucocorticoids to reverse severe kidney transplant rejection.
The combined administration of glucocorticoids and azathioprine was subsequently introduced as maintenance immunosuppressive therapy [2]. Significant benefits with this regimen helped transform transplantation from an experimental, infrequently used procedure to a widespread, extremely successful clinical option.
Most transplant centers administer large doses of glucocorticoids perioperatively and immediately postoperatively. This usually consists of a "pulse" intraoperative dose of 5 to 10 mg/kg of methylprednisolone, which is followed by 1 mg/kg per day of prednisone. This is subsequently tapered to approximately 0.05 to 0.1 mg/kg per day of prednisone by one year or less. (See "Kidney transplantation in adults: Maintenance immunosuppressive therapy".)
However, the immunosuppressive benefits derived from this glucocorticoid regimen are counterbalanced by the possible induction of numerous major adverse effects (see "Major side effects of systemic glucocorticoids"). These include the following:
●Cortical bone mass quickly declines, possibly leading to osteopenia, skeletal fractures, and avascular necrosis. (See "Kidney transplantation in adults: Persistent hyperparathyroidism after kidney transplantation".)
●Established diabetes is worsened, while de novo cases of diabetes may develop. (See "Kidney transplantation in adults: Posttransplantation diabetes mellitus".)
●Wound healing is a significant problem, particularly among the obese.
●There are alterations in lipid metabolism, possibly resulting in an atherogenic milieu. (See "Kidney transplantation in adults: Lipid abnormalities after kidney transplantation".)
Other significant adverse effects include an enhanced risk of cataract formation, hypertension, and obesity.
To minimize toxicity and decrease overall immunosuppression, tapering and ultimate withdrawal of glucocorticoids has been attempted. Cessation of glucocorticoid therapy is often associated with a fall in blood pressure and, in diabetic patients, better glycemic control; total cholesterol levels also fall, but there is an equivalent reduction in high-density lipoprotein (HDL)-cholesterol and, therefore, an uncertain effect on cardiovascular risk [3] (see "Kidney transplantation in adults: Lipid abnormalities after kidney transplantation"). Prevention of osteopenia and aseptic necrosis of bone are other potential benefits; there are, however, limited data to confirm these results.
Minimizing glucocorticoid use in the setting of organ transplantation has therefore been a goal for many years [4-6]. In the United States, in 2004, glucocorticoid avoidance regimens were administered to 23 percent of all first kidney transplant recipients [7]. Among those discharged on glucocorticoids (approximately 77 percent), approximately 10 percent had glucocorticoids completely withdrawn by one year posttransplant. Further, in 2007, approximately 30 percent of kidney transplant recipients were discharged on an immunosuppressive regimen that did not include glucocorticoids, and this percentage has remained constant [8,9]. Thus, although glucocorticoids are administered to the majority of kidney transplant recipients, strategies aimed at minimizing or avoiding these agents are increasingly used.
A review of glucocorticoid withdrawal or avoidance in the kidney transplant patient with stable kidney function is presented here. Withdrawal of immunosuppression in the patient with a failed kidney allograft is presented separately. (See "Kidney transplantation in adults: Management of the patient with a failed kidney transplant".)
MINIMIZING GLUCOCORTICOID USE — Compared with conventional immunosuppressive regimens, exposure to glucocorticoids can be further minimized via several different strategies:
●Lower doses administered earlier after transplantation
●Complete withdrawal, which can either be performed early after transplantation (approximately three to six months postsurgery) or at a later time (after one year)
●Complete avoidance, which most frequently has been utilized with a calcineurin inhibitor-based immunosuppressive regimen and polyclonal antibody induction therapy
The effectiveness of such strategies is dependent in part upon the ability of the remaining nonglucocorticoid immunosuppressive agents to suppress the anti-allograft immune response. The continuing introduction of more selective and possibly improved immunosuppressive agents (compared with traditional drugs), such as targeted-antibody preparations, may eventually permit a completely glucocorticoid-free maintenance regimen.
Several registry studies and meta-analyses have evaluated the outcomes associated with minimizing glucocorticoid use [10-16]. In general, the risk of acute rejection is markedly increased with the withdrawal of glucocorticoids weeks to months after transplantation [16,17]. However, some claim that overall benefits may be found in certain patients if glucocorticoids are discontinued during the first week after transplantation. As an example, the 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines suggest that glucocorticoids may be discontinued during the first week after transplantation in patients who are at low immunologic risk and who also receive induction therapy [17].
●A systematic review of 48 randomized trials (7803 patients) comparing glucocorticoid avoidance or withdrawal with glucocorticoid maintenance, or comparing glucocorticoid avoidance with glucocorticoid withdrawal, found no significant difference in patient mortality, death at one year posttransplantation, or graft loss among adults [16]. However, the risk of acute rejection significantly increased in patients treated with glucocorticoids for fewer than 14 days after transplantation. Continuation of glucocorticoids was not associated with a difference in harmful events, such as infection and malignancy, in adult kidney transplant recipients.
●An analysis of national transplant registry, pharmacy fill, and medical claims data for Medicare-insured kidney transplant recipients from the United States Renal Data System found that glucocorticoid-free maintenance immunosuppression was associated with a reduced risk of pneumonia, sepsis, and diabetes but also a higher risk of graft failure [18].
●Early glucocorticoid withdrawal may be particularly deleterious in patients who have delayed graft function (DGF) [19,20]. An analysis of 110,019 adult deceased-donor kidney transplant recipients between 2005 and 2017 found that among those who experienced DGF, early glucocorticoid withdrawal was associated with an increased risk of allograft loss compared with continued glucocorticoid maintenance (adjusted hazard ratio [aHR] 1.16, 95% CI 1.08-1.26) [20].
Thus, we do not agree with the KDIGO guidelines. Overall, we consider that the published evidence suggests that low-dose glucocorticoid therapy should be continued indefinitely at low doses of prednisone of 5 mg per day. Many of the trials that have shown benefit with glucocorticoid avoidance or are ongoing have evaluated short-term outcomes in patients at relatively low risk of adverse outcomes. Many of these avoidance trials are also enrolling a low number of African Americans, a group at particularly high risk of rejection. Outcomes are significantly affected by these strategies, a subject that is discussed in the relevant sections elsewhere within this topic review.
Very low dose maintenance therapy — As previously mentioned, most centers attempt to taper glucocorticoids to approximately 0.05 to 0.1 mg/kg per day of prednisone (or even less) by one year or sooner. In the absence of acute rejection, for example, we generally reduce glucocorticoids to a dose of 5 mg per day by one month following kidney transplantation. Overall, the benefit of maintenance low-dose glucocorticoids at the doses utilized may include improved immunosuppression, modulation of calcineurin inhibitor nephrotoxicity, reduced risk of cytopenias, and/or ability to avoid calcineurin inhibitor use.
Such doses are associated with decreased rejection and avoidance of chronic kidney allograft nephropathy compared with early glucocorticoid withdrawal/avoidance. This was best shown in the only prospective, well-designed study that compared very early glucocorticoid cessation to low-dose, long-term glucocorticoid therapy in kidney recipients receiving modern maintenance immunosuppression. In this trial, 386 patients were randomly assigned to glucocorticoid withdrawal at one week posttransplant or continuance of glucocorticoids [21]. All patients received antibody induction therapy with either rabbit antithymocyte globulin (68 percent) or intereukin-2 receptor antibody (32 percent). Maintenance therapy consisted of tacrolimus, mycophenolate mofetil, and seven days of glucocorticoids followed by blinded randomization to either the glucocorticoid withdrawal group or a glucocorticoid continuation group that was tapered to 5 milligrams of prednisone daily by six months after transplant.
At follow-up at five years, the following results were reported:
●There was no significant difference in the primary composite endpoint (death, allograft loss, or moderate/severe rejection) or in any of the individual components.
●The very early withdrawal group was associated with significant increases in the incidence of chronic allograft nephropathy (10 versus 4 percent), as well as biopsy-proven acute rejection (18 versus 11 percent). Given that the rate of moderate/severe rejection was similar in the two groups, these findings suggest that very early withdrawal increased the risk of mild rejection.
●In terms of glucocorticoid-associated side effects, there were no significant differences in blood pressure, new-onset diabetes, serum cholesterol, or low-density lipoprotein (LDL) levels and rates of bone fracture or cataracts.
Although the authors concluded that very early withdrawal is safe and provides similar five-year kidney allograft outcomes, this strategy resulted in double the rate of chronic allograft nephropathy compared with continuance of glucocorticoid therapy. These findings suggest that continued maintenance therapy is preferred to very early withdrawal. (See "Kidney transplantation in adults: Maintenance immunosuppressive therapy" and 'Summary and recommendations' below.)
Withdrawal several weeks to months after surgery — The benefits of glucocorticoid withdrawal within several weeks to months after surgery were quickly realized to be accompanied by a significantly increased risk of acute rejection and possible decreased long-term allograft survival. This is particularly true if withdrawal is performed less than three to six months after surgery [22,23].
In general, early cessation of glucocorticoids is associated with an increased incidence of acute rejection and a possible decrease in long-term (more than two years) graft survival. As a result, early glucocorticoid withdrawal or avoidance has been abandoned by most transplant centers for the majority of patients. (See 'Summary and recommendations' below.)
The adverse effects of early withdrawal upon allograft survival appear to emerge only after an extended period of follow-up [22,24,25]. In some studies, such immunosuppressive strategies did not affect early (less than two years) allograft survival. By comparison, significantly decreased long-term survival was reported in a multicenter Canadian trial, which evaluated the outcome of 523 stable transplant recipients who were randomly assigned at day 90 following kidney transplant to placebo or alternate-day prednisone [26]. Adverse allograft survival results associated with total glucocorticoid withdrawal were not evident until follow-up at five years (73 and 85 percent for the placebo and prednisone groups, respectively).
The success with glucocorticoid withdrawal may depend in part upon the effectiveness of the remaining agents that constitute the immunosuppressive regimen. Studies evaluating glucocorticoid withdrawal in patients treated with calcineurin inhibitors and/or mycophenolate mofetil have largely shown worse outcomes, except in patients receiving antilymphocyte induction therapy or in patients at low to standard risk [25,27-32].
Withdrawal years after transplantation — The results of studies evaluating withdrawal at later time points are conflicting, demonstrating the need for caution concerning any glucocorticoid withdrawal regimen. We believe that there is little long-term benefit and a small but clear risk observed in patients withdrawn from small doses of glucocorticoids after one year. Patients chosen for glucocorticoid withdrawal at our center have a low risk profile and an identifiable potential benefit for withdrawal. Thus, we have withdrawn glucocorticoids after one year in less than 1 percent of kidney transplant patients at our center.
The following is an overview of some of the studies that have examined this issue [11,33-40]:
●A meta-analysis published in 2000 of 20 glucocorticoid withdrawal studies reported that withdrawal was also associated with a higher relative risk of graft failure (relative risk = 1.34) and an increased risk of acute rejection (14 percent) [11]. These adverse results were worse than those from studies evaluating the outcomes of cyclosporine withdrawal.
●A large, prospective, but nonrandomized, European study reported that glucocorticoid withdrawal may result in improved graft and patient survival versus that observed with matched controls [36]. In this multicenter study, 1110 cadaveric kidney recipients underwent slow glucocorticoid withdrawal after at least six months posttransplantation. Matched controls selected from the database by the investigators were derived from the Collaborative Transplant study database. Both groups were similar, including a low risk for rejection, except that the controls had lower serum creatinine concentrations (less than 1.47 mg/dL [130 micromol/L] versus less than 2.94 mg/dL [260 micromol/L]) for the withdrawal patients.
At seven years, superior benefits with withdrawal were noted for graft survival (82 versus 75 percent), patient survival (89 versus 84 percent), and death-censored graft survival (92 versus 88 percent). There were no differences in rates of acute rejection and allograft dysfunction.
Although intriguing because of demonstrable clinical benefit (better bone density in the withdrawal group), significant limitations of this study include the lack of randomization, heterogeneous immunosuppressive regimens, and loose guidelines for timing and duration of glucocorticoid withdrawal [41]. Further, at any point in time during the study, approximately 30 to 40 percent of patients were treated with glucocorticoids, suggesting an adverse clinical event.
●Limited data suggest that the use of mycophenolate mofetil in those undergoing late withdrawal may not be associated with adverse effects [37-39]. In one study, 212 patients receiving triple immunosuppressive therapy consisting of mycophenolate mofetil (1000 mg twice daily), cyclosporine (trough level of 125 to 175 ng/mL), and prednisone (without antibody induction therapy) were randomly assigned at six months posttransplant to prednisone withdrawal, cyclosporine withdrawal, or continued triple therapy [38]. At two years posttransplant, the incidence of biopsy-proven acute and chronic rejection was higher in the prednisone-withdrawal than the control group (4 and 1.4 percent for acute and 5 and 1.4 percent for chronic rejection, respectively); by comparison, the cyclosporine-withdrawal group had a significantly higher incidence of acute and chronic rejection (22 and 14 percent, respectively). At 18 months after cessation of glucocorticoid therapy, the prednisone-withdrawal group, compared with controls, had a lower mean blood pressure and similar kidney function and patient and graft survival.
Glucocorticoid-free regimens — Although glucocorticoid avoidance is popular, it is unlikely to provide the best overall risk-to-benefit ratio with maintenance immunosuppressive therapy in kidney transplantation. Many glucocorticoid avoidance protocols have chosen low-risk individuals and utilized aggressive induction therapy. We do not recommend glucocorticoid-free immunosuppressive regimens, based on existing data.
The following is an overview of the data, including a historical perspective, that have examined the efficacy of glucocorticoid-free regimens in kidney transplantation.
Glucocorticoid-free immunosuppression was attempted with some success following the introduction of cyclosporine in the 1980s. As an example, a multicenter, European study of 232 cadaveric kidney transplants demonstrated a one-year allograft survival rate of 77 percent with cyclosporine only as compared with 63 percent in the azathioprine and prednisone control group [42].
Since the 1990s, a transplant group in Denmark has also successfully adopted a glucocorticoid-free immunosuppression strategy (including its avoidance in treating rejection) in combination with induction therapy utilizing rabbit antithymocyte globulin (Thymoglobulin) [43,44]. In a report summarizing their more recent experience, maintenance immunosuppressive therapy consisted of cyclosporine and mycophenolate mofetil in 100 consecutive patients [44]. Rejections, which were treated with antilymphocyte therapy without glucocorticoids, occurred in only 13 percent of patients. Allograft survival was excellent, with one-, two-, three-, and four-year graft survivals of 97, 96, 90, and 82 percent, respectively.
A similar protocol with glucocorticoid avoidance in 51 low-risk, living-donor recipients utilized antithymocyte globulin induction therapy, mycophenolate mofetil, and cyclosporine [45]. Prednisone was discontinued on postoperative day 6. Ten percent of patients experienced acute rejection, with a 98 percent overall allograft survival at one year. Graft function was no different than historic controls.
The five-year experience from the same center in 589 relatively low-risk patients (71 percent living donor, with some patients also receiving tacrolimus and sirolimus) demonstrated comparable results, with decreased cytomegalovirus (CMV) infections, diabetes mellitus, cataracts, avascular necrosis, and fractures as compared with historical controls from the late 1990s [46].
Ten-year outcomes were reported from the same group [47]. Among 1241 adult primary transplant recipients (791 living donor and 450 deceased donor) who received allografts between 1999 and 2010, the following outcomes were reported for living-donor and deceased-donor transplants at 10 years:
●Patient survival was 71 and 62 percent for living-donor and deceased-donor transplants, respectively.
●Graft survival was 61 and 51 percent, respectively.
●Death-censored graft survival was 79 and 80 percent, respectively.
●Acute rejection rates were 31 and 25 percent, respectively.
Both patient and graft survival were comparable with national data reported by the Scientific Registry of Transplant Recipients (SRTR) in 2009. The reported overall rate of new-onset diabetes was lower in this group of patients than that reported in historical controls. Other side effects of glucocorticoids, including cataracts, avascular necrosis, and CMV, were lower in certain subgroups.
However, as in prior reports that described favorable outcomes with glucocorticoid avoidance strategies, the cohort of patients included in this analysis was relatively low risk compared with transplant recipients encountered elsewhere, with a predominance of living-donor kidney recipients, non-African Americans, and nonsensitized recipients. In addition, the patients in the study were compared with historical controls who received higher doses of glucocorticoids for sustained periods of time [48].
In addition, the one-year acute rejection rate in the deceased-donor group (16 versus 11 percent in living donors, p = 0.07) raises the concern that this strategy must be considered carefully in high-risk individuals.
Additional immunosuppressive agents, such as sirolimus, tacrolimus, basiliximab, and antithymocyte globulin, have been introduced to try to permit glucocorticoid-free immunosuppression [46,49-64]. The following studies illustrate the range of findings:
●Three-hundred kidney transplant recipients were randomly assigned to a second-day glucocorticoid withdrawal group or glucocorticoid therapy, with common immunosuppression being basiliximab for induction therapy and calcineurin inhibitor plus mycophenolate mofetil or sirolimus for maintenance therapy [60]. At three years, acute rejection rates, patient and allograft survival, incidence of chronic allograft nephropathy and subclinical rejection, and kidney function were similar in both arms. By comparison, a significantly lower incidence of posttransplant diabetes mellitus was observed in the glucocorticoid withdrawal group (4 versus 21 percent).
●One single-center study reported the graft and patient survival of 349 patients administered a glucocorticoid-free regimen consisting of antithymocyte globulin, either mycophenolate mofetil or sirolimus, and a calcineurin inhibitor [53]. Acute rejection-free graft survival at one and three years was 94 and 92 percent, respectively, and patients and allograft survival at three years was 95 and 93 percent, respectively.
Long-term experience with glucocorticoid-free immunosuppression in patients is limited [21,65]. In the previously discussed study comparing very early glucocorticoid cessation to low-dose, long-term glucocorticoid therapy in kidney recipients receiving modern maintenance immunosuppression, there was no significant difference at five years in the primary composite endpoint (death, allograft loss, or moderate/severe rejection) or in any of the individual components [21] (see 'Very low dose maintenance therapy' above). However, the very early withdrawal group was associated with significant increases in the incidence of chronic allograft nephropathy and biopsy-proven acute rejection. A single-center, four-year study found that allograft and patient survival were similar among those with glomerulonephritis treated without glucocorticoids, patients without glomerulonephritis treated without glucocorticoids, and recipients with glomerulonephritis treated with glucocorticoids [65].
Many of the previously cited trials evaluated outcomes in patients at relatively low risk of adverse outcomes. Some trials have also assessed whether glucocorticoid-free regimens are feasible in patients at increased risk, including African Americans and presensitized patients. As examples [27,57,66-68]:
●In one study of rapid prednisone discontinuation among 79 patients at high risk (such as African Americans or presensitized recipients), three-year allograft survival was approximately 95 percent [66].
●A second study of 206 kidney recipients (including 103 African Americans) with a maintenance regimen of calcineurin inhibitor plus mycophenolate mofetil or sirolimus found that one-year patient and allograft survival was 96 and 88 percent for African Americans and 97 and 89 percent for non-African Americans, respectively [67]. However, an increased acute rejection rate was observed in African Americans (16 versus 13 percent). At five years, allograft and patient survival remained the same for both groups [68]. The results from this single center require verification from either registry or other large, single-center analyses.
A related issue is the use of maintenance glucocorticoids in patients on steroid avoidance regimens who are treated with steroids for an acute rejection episode. One retrospective, single-center study found that allograft survival was not affected by whether the patient continued to receive steroids, while maintenance steroids lowered the risk of a second acute rejection episode [69]. Further study is required to understand the role of maintenance steroids in this setting.
Choice of immunosuppressive agent — The optimal glucocorticoid-free regimen is not known. A prospective, observational study of 82 consecutive transplant recipients found better overall graft survival associated with tacrolimus/mycophenolate mofetil compared with tacrolimus/sirolimus at 8.5 years (91 versus 70 percent, respectively) [70]. By three months after transplantation, estimated glomerular filtration rate (GFR) was lower in the tacrolimus/sirolimus group (48 versus 60 mL/min/1.73 m2). One prospective, randomized trial has shown that tacrolimus plus mycophenolate mofetil is also better tolerated compared with sirolimus plus mycophenolate mofetil [71]. In this study, 122 kidney transplant recipients who received tacrolimus and mycophenolate mofetil with rapid glucocorticoid withdrawal for the first month after transplant were assigned to receive mycophenolate mofetil, given with either sirolimus or tacrolimus. More patients in the sirolimus group withdrew during the two-year period of the study compared with tacrolimus (63 versus 18 percent, respectively). Reasons for withdrawal were related to rejection or medication side effects. The high withdrawal rate may have been due to the absence of glucocorticoids, which may modulate some of the side effects of the sirolimus.
Recurrent glomerulonephritis — Steroid avoidance is associated with increased risks of recurrent glomerulonephritis:
●In one large, retrospective study, rapid steroid withdrawal was associated with a higher risk of recurrent glomerulonephritis compared with continued steroids (hazard ratio [HR] 4.86, 95% CI 2.34-10.07) [72]. This study showed no difference between groups in patient, graft, or death-censored graft survival, suggesting no benefit and possible harm from steroid avoidance in patients with a history of glomerulonephritis.
●In a registry study of 1521 kidney transplant recipients in the Australia and New Zealand Dialysis and Transplant Registry, continued glucocorticoid use was strongly related to a reduced risk of immunoglobulin A (IgA) recurrence [73].
●In a study of 124 kidney transplant recipients who had IgA nephropathy as the primary disease, 75 patients received steroid-based immunosuppression (15 undergoing late steroid withdrawal), and 49 received steroid-free immunosuppression [74]. Recurrent IgA nephropathy was diagnosed by clinically indicated allograft biopsy in 27 of 124 patients over a median follow-up of 6.86 years.
By multivariate analysis, the risk of IgA nephropathy recurrence was higher in patients managed with a steroid-free protocol compared with the group that continued to receive steroids (HR 8.59, 95% CI 3.03-24.38).
SUMMARY AND RECOMMENDATIONS — Glucocorticoid withdrawal following kidney transplantation remains a controversial issue. Several centers routinely discontinue glucocorticoids, while others continue maintenance glucocorticoids indefinitely [75-78]. The use of polyclonal antibody induction therapy appears to facilitate glucocorticoid withdrawal.
Our policy is to individualize therapy based upon a careful assessment of the risk-benefit ratio. In general, our opinion is that, in most patients, long-term calcineurin inhibitor toxicity outweighs the long-term toxicity of low-dose glucocorticoids. We therefore administer low-dose glucocorticoid therapy indefinitely as part of the maintenance immunosuppressive regimen.
Glucocorticoid minimization — In the absence of acute rejection, there is little utility in maintaining patients on large doses of glucocorticoids or in tapering glucocorticoids over prolonged periods of time. We therefore reduce the prednisone dose to 20 mg daily on postoperative day 3, with tapering to 5 mg daily by five weeks following transplantation. (See "Kidney transplantation in adults: Maintenance immunosuppressive therapy".)
Withdrawal several months after surgery — We do not recommend early withdrawal (less than six months following transplantation) in the majority of patients. This is because the benefits of withdrawal have not been consistently reproduced, and there is a clear risk of acute rejection and decreased kidney function. The long-term effect of glucocorticoid withdrawal is unknown.
If early glucocorticoid withdrawal is attempted, it seems prudent to only do so in those who have received lymphocyte-depleting therapy with antithymocyte globulin and possibly alemtuzumab. The data to support alemtuzumab are limited. It is thus prudent to monitor these patients aggressively, perhaps even with protocol biopsies.
Late withdrawal — It is less clear whether late withdrawal (greater than one year) should or should not be recommended. The failure of withdrawal in up to 40 percent of patients in most studies emphasizes the need for caution. Late withdrawal has been successfully performed in some centers, but its effect upon long-term allograft function and the risk of chronic rejection has not been conclusively evaluated. Several studies have also suggested that many patients do not obtain any substantial, clinically significant benefit by eliminating low-dose glucocorticoid therapy. In addition, methods of identifying candidates who will suffer adverse renal consequences from withdrawal are not available.
Successful withdrawal protocols use a slow taper over a two- to four-month period. With stable patients, one successful regimen is to taper the dose of prednisone by 1 mg/day every week until the dose is 5 mg/day, which is then changed to 10 mg every other day, with a weekly reduction of 1 mg every other day until the dose is completely tapered [33]. A second protocol reduces the dose every two weeks by 2.5 mg/day until the prednisone dose is tapered to zero [34].
We believe that there is little long-term benefit and a small but clear risk observed in patients withdrawn from small doses of glucocorticoids after one year. Patients chosen for glucocorticoid withdrawal at our center have a low risk profile and an identifiable potential benefit for withdrawal. Thus, we have withdrawn glucocorticoids after one year in less than 1 percent of kidney transplant patients at our center.
Glucocorticoid avoidance — Glucocorticoid avoidance may eventually be found to provide the best overall risk-to-benefit ratio with maintenance immunosuppressive therapy in kidney transplantation. Glucocorticoid avoidance protocols have been used successfully and are undergoing extensive evaluation.
However, many of these protocols, although not all, and other anecdotal reports have chosen low-risk individuals and utilized aggressive lymphocyte-depleting induction therapy. In addition, if decreases in the intensity of immunosuppression are needed in some patients with these regimens (consisting of dual therapy with a calcineurin inhibitor and an antimetabolite) because of an infectious event or drug toxicity, the next alternative for maintenance immunosuppressive therapy is monotherapy. We cannot universally recommend glucocorticoid–free immunosuppressive regimens based on the best evidence-based data.
