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Published ahead of print on July 6, 2006
Clin J Am Soc Nephrol 1: 1029-1038, 2006
© 2006 American Society of Nephrology
doi: 10.2215/CJN.00790306
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Transplantation

Effect of Prednisone versus No Prednisone as Part of Maintenance Immunosuppression on Long-Term Renal Transplant Function

Lorenzo G. Gallon*, Johan Winoto*, Joseph R. Leventhal{dagger}, Michele A. Parker{ddagger}, and Dixon B. Kaufman{dagger}

* Department of Medicine, Division of Nephrology, and {dagger} Department of Surgery, Division of Solid Organ Transplantation, Northwestern University, Chicago, Illinois; and {ddagger} Duke Cardiovascular Center, Duke University Medical School, Durham, North Carolina

Address correspondence to: Dr. Lorenzo Gallon, 675 N. St. Clair, Galter-Pavilion 17-200, Chicago, IL 60611. Phone: 312-695-4457; Fax: 312-695-9194; E-mail: l-gallon{at}northwestern.edu


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Corticosteroids have been a component of maintenance immunosuppression for renal transplant since the 1960s and have helped to reduce the rate of acute rejection. Corticosteroids, however, have many adverse effects, and with the development of new immunosuppressive medications, many transplant centers have adopted protocols that eliminate or completely avoid the use of corticosteroids. Despite promising short-term results, the impact of corticosteroid elimination on long-term kidney function still is unclear. This single-center, retrospective, sequential study analyzed 212 renal transplant patients with a median follow-up of 5 yr. All patients received induction with IL-2 receptor antagonist and maintenance immunosuppression with mycophenolate mofetil and tacrolimus. Ninety-six patients were maintained on chronic prednisone, and 116 were maintained without chronic prednisone (rapid steroid elimination). Kaplan-Meier patient and graft survival at 7 yr after transplantation were not statistically different between the two groups. Rate and severity of acute cellular rejection were similar. Furthermore, the slope of GFR decline per month at 5 yr after transplantation was not statistically different between the two groups. Prednisone-treated patients had a significantly higher incidence of hyperlipidemia and posttransplantation diabetes when compared with patients with rapid steroid elimination. It was concluded that with the current immunosuppressive medications, the use of chronic prednisone to maintain long-term kidney function and prevent acute cellular rejection is not justified.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Corticosteroids have played a critical role in the evolution of organ transplantation. Steroids have been the cornerstone of immunosuppressive regimens to treat and prevent acute rejection in organ transplantation. The precise mechanism of action of glucocorticoids is not fully understood, although it is apparent that it is multifaceted, involving both direct and indirect mechanisms and affecting proximal and distal events of T cell activation (1).

Long-term administration of corticosteroids also is known to be associated with numerous adverse effects that lead to increased patient morbidity and mortality after renal transplantation. The adverse effects of corticosteroids, including new-onset diabetes, hyperlipidemia, hypertension, growth retardation, accelerated bone loss, weight gain, avascular necrosis, cataracts, cosmetic changes, depression, psychotic behavior, and others, have been well documented (2–7). There also is evidence that they may interfere with the tolerogenic pathways of organ acceptance (8,9). In addition to affecting the morbidity and the quality of life of renal transplant recipients, corticosteroids increase the long-term cost of their medical care (10).

In the pre–mycophenolate mofetil (pre-MMF) era, despite the adverse effects associated with steroid therapy, the risk for increased rejection with steroid discontinuation often has outweighed the potential benefits of improved quality of life (11–14). Results from a meta-analysis of seven randomized, controlled trials during this period suggested that avoiding steroid therapy from the time of transplantation or withdrawing steroid therapy at some time after transplantation increased the risk for acute allograft rejection (2). In addition, results from a placebo-controlled trial organized by the Canadian Multicenter Transplant Group concluded that steroid withdrawal at 3 mo after transplantation in recipients who were maintained on cyclosporine (CsA) alone resulted in deterioration of renal function that could be appreciated only after 5 yr of follow-up (15). This discouraged the widespread use of steroid-sparing regimens.

During the past decade, the adoption of induction protocols with either lymphocyte-depleting agents or IL-2 receptor antagonist (IL-2-RA) (16,17) and the use of newer immunosuppressive medications such as MMF (18–20), sirolimus, and tacrolimus (21) have caused many to reconsider the use of steroids as a maintenance agent. Various strategies have been adopted by various centers to reduce steroid exposure, including low-dose steroids, alternate-day steroids, early/late withdrawal, rapid steroid discontinuation, and steroid avoidance. Each strategy may have different benefits and limitations. Two large, multicenter, double-blind, randomized, prospective studies that analyzed a combination of CsA microemulsion, steroids, and MMF with or without antilymphocytic induction therapy showed a significantly higher incidence of acute rejection episodes at 12 mo with withdrawal of steroids (22,23). Most of the rejection episodes easily were reversible. These trials concluded that it was safe to withdraw steroids in a vast majority of the patients with metabolic benefits, predominantly in nonblack patients with good graft function (23). The results of a subgroup analysis in one of these studies showed a smaller difference in acute rejection rates between patients in the control and no steroid groups who received induction compared with those who did not receive induction (22). Additional studies using steroid-free/withdrawal protocols that have used induction agents have reported lower acute rejection rates than those reported in these two trials (24–29).

Steroid avoidance or rapid elimination of steroids may have an advantage over steroid withdrawal. Steroid avoidance protocols may avoid the long-term risks of steroid use and the increased risk for rejection when the steroids are withdrawn. Birkeland (24) and Khwaja et al. (30) reported excellent long-term graft survival and function (3 and 4 yr, respectively) with very low rejection rates. In other studies, a slight increase in acute rejection episodes, especially in the early posttransplantation period, was observed; these were easily reversible, and their impact on long-term graft survival is unclear at this time (27,31–34). In this context, we recently published a retrospective analysis from our transplant center of an examination of the impact of two different induction agents, alemtuzumab (Campath 1H, Berlex Laboratories, Wayne, NJ) versus basiliximab (Simulect, Novartis Pharmaceuticals, East Hanover, NJ) on long-term patient and graft survival for patients who were maintained on prednisone-free immunosuppression with tacrolimus and MMF (35). We found that long-term patient and graft survival rates across an ethnically diverse kidney transplant recipient population were equivalent in the two groups analyzed. At 12 mo after transplant, actual rejection rates for recipients of alemtuzumab or basiliximab were 14.9 and 13.5%, respectively.

To examine further the impact of prednisone-free immunosuppression on long-term renal allograft function, we designed the following study in kidney transplant recipients who were maintained on tacrolimus/MMF with the aim to (1) compare retrospectively two sequential protocols, one of rapid steroid elimination versus chronic steroid use as a part of maintenance immunosuppression on renal allograft survival and (2) assess whether possible differences in the long-term efficacy of these two immunosuppressive regimens was related to differences in their antirejection effects and/or on renal function.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Study Design and Patients
This was a single-center, retrospective, sequential study. Both groups of renal transplant patients received the same induction therapy with IL-2-RA and were maintained with tacrolimus/MMF with (Pred+ group) or without (Pred– group prednisone). Renal transplants in the Pred+ group (n = 96) were performed from April 1998 through May 1999. The mean follow up was 4.7 ± 1.3 yr. Renal transplants in the Pred– group (n = 116) were performed from June 1999 through November 2000. The mean follow-up was 4.5 ± 1.0 yr. The study was approved by the Institutional Review Board of Northwestern University.

A total of 212 renal transplant patients with a median follow-up of 5 yr after transplantation were part of the analysis. For each patient, the following information was collected: Date of transplantation, age, gender, race, causes of ESRD, panel-reactive antibodies, delayed graft function, donor age, donor source, degree of HLA mismatch, graft survival, patient survival, acute rejection episodes and severity, GFR at different time points after transplantation, tacrolimus trough levels at different time points after transplantation, and MMF dosage at different time points after transplantation.

Immunosuppressive Regimens
All patients received perioperative intravenous corticosteroid therapy of 500 mg of methylprednisolone on day 0, 250 mg on day 1, and 125 mg on day 2. All patients received the anti–IL-2-RA basiliximab at day 0 and day 2 at the dose of 20 mg intravenously. Tacrolimus (Prograf, Astellas Pharma, Deerfield, IL) was started on postoperative day 1. Target 12-h trough levels for tacrolimus were 8 to 10 ng/ml during the first 3 mo, 7 to 9 ng/ml from 4 to 6 mo after transplantation, and 6 to 8 ng/ml thereafter. MMF (Cellcept, Roche Pharmaceuticals, Nutley, NJ) was started on postoperative day 1 with a target dose of 2.5 g/d. MMF doses were adjusted as indicated for leukopenia. This immunosuppressive regimen (moderate- to high-dose of MMF with low to normal tacrolimus trough levels) was used with the intent of avoiding long-term nephrotoxicity from tacrolimus.

A total of 96 of 212 patients were maintained on chronic prednisone (Pred+ group, dose between 5 and 7.5 mg/d) throughout the posttransplantation period. A total of 116 of 212 patients were maintained without the use of chronic prednisone (Pred– group) as a part of the maintenance immunosuppression after the perioperative intravenous corticosteroid therapy of 500 mg of methylprednisolone on day 0, 250 mg on day 1, and 125 mg on day 2. No further steroids were given during the posttransplantation period (rapid steroid elimination). After transplantation, trough levels for tacrolimus were monitored daily during the first week and twice weekly during the first month, once a week in months 2 to 3, and on a monthly basis thereafter.

All cytomegalovirus (CMV)-seronegative and -seropositive patients who received a kidney from a CMV-positive donor were treated with CMV prophylaxis with valganciclovir 450 mg orally once day for 6 mo. Seronegative recipients who received a kidney from a CMV-negative donor did not receive CMV prophylaxis. Prophylactic therapy for Pneumocystis carinii pneumonia was administered to all patients for up to 1 yr after transplantation. For fungal prophylaxis, patients were given oral clotrimazole or Nystatin for 3 mo after transplant.

Exclusion Criteria for Rapid Steroid Elimination
From June 1999 through November 2000, when we implemented at our center rapid steroid elimination, some patients were excluded from this protocol. These were patients who were on long-term prednisone before the renal transplant, to control other underlying diseases such as systemic lupus erythematosus, rheumatoid arthritis, and asthma and, as a consequence, required steroids as part of their medical therapy.

Diagnosis and Treatment of Acute Rejections
All rejection episodes were biopsy proven. All biopsies were graded using the Banff 97 classification. Acute cellular rejections (ACR) were treated, on the basis of severity, with 500 mg of methylprednisolone intravenously for 3 d followed by a 1-wk course of prednisone taper or with an antilymphocyte antibody therapy (Thymoglobulin or OKT3) for 14 d. No specific immunosuppressive therapy or modification of the immunosuppressive regimen was offered to patients with biopsy-proven chronic rejection.

Renal Allograft Function Measurement
GFR was calculated at different time points after transplant (3, 6, 12, 24, 36, 48, and 60 mo) using the abbreviated Modification of Diet in Renal Disease (MDRD) equation (36).

Outcomes
Outcomes of the study were patient and graft survival, incidence and severity (determined by histologic grade) of acute renal allograft rejection during the posttransplantation period, and graft function during the 5 yr of follow-up determined with the MDRD equation at different time points after transplant. Graft loss was defined as return to dialysis.

Safety Variables
Safety was assessed by monitoring adverse events during the course of the study. In particular, we monitored the incidence and the severity of hyperlipidemia, infections, malignancy, and de novo post transplantation diabetes. Diabetes was defined by using the 1997 American Diabetes Association criteria.

Statistical Analyses
Continuous data are expressed as mean ± SD. Between-group comparisons of continuous data were made using two-sample t test; discrete data were compared using {chi}2 tests. Patient and graft survival as well as time to acute rejection after transplantation were assessed using Cox proportional hazards models. Mixed-effects linear models were used to assess the change in renal function (GFR) over time as well as to evaluate the differences between groups. All statistical tests were two tailed, and P < 0.05 was regarded as significant. The outcomes variables between the two groups (Pred+ versus Pred–) were compared using the intention-to-treat analysis.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
Patient Demographics and Donor–Recipient Characteristics
There were no significant differences between the two groups when recipient age, gender, ethnicity, incidence of delayed graft function, induction therapy, and panel-reactive antibody titer before transplantation were compared (Table 1). The mean age of donors in the Pred+ group was significantly higher than that in the Pred– group (41.4 ± 12.0 versus 35.6 ± 11.7 yr; P = 0.0006). The percentage of patients who received a living-donor kidney was higher in the Pred– group than in the Pred+ group (61 versus 42%; P = 0.004).


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  		Table 1. Patient demographics and donor–recipient characteristicsa

 
Patient and Graft Survival
Seven-year Kaplan-Meier patient survival rates were not significantly different between the Pred+ and Pred– groups (P = 0.06; Figure 1A). Seven-year Kaplan-Meier graft survival rates (death censored) were not significantly different between the Pred+ and Pred– groups (P = 0.27, Figure 1B). Seventy-seven percent of patients in the Pred+ group and 74% of patients in the Pred– group reached 5 yr of posttransplantation follow-up (n = 74 and 86, respectively).


Figure 1
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  		Figure 1. (A) Cumulative patient survival in Pred+ versus Pred– at 7 yr after transplantation. The Kaplan-Meier curves are not significantly different (P = 0.06). Respectively, 77 and 74% of patients in the Pred+ and Pred– groups reached 5 yr of posttransplantation follow-up. (B) Cumulative renal allograft survival in Pred+ versus Pred– at 7 yr after transplantation. The Kaplan-Meier curves are not significantly different (P = 0.27).

 
Drug Monitoring
Blood trough levels of tacrolimus during the 5-yr posttransplantation follow-up were similar in both groups (Table 2). MMF dosage during the posttransplantation follow-up also was similar in both groups (Table 2).


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  		Table 2. Tacrolimus trough levels and MMF dosage during 5-yr post-Tx follow-upa

 
Incidence of Acute Rejection
During the entire posttransplantation follow-up, 28 (29%) patients in the Pred+ group experienced ACR compared with 23 (20%) patients in the Pred– group. This difference was not statistically significant (P = 0.12; Figure 2). When the incidence of acute rejection episodes was analyzed also according to the donor source (living donors and deceased donors), an NS significant difference was found between the two groups (data not shown). Seventy percent of the acute rejections in the Pred– group occurred early (<30 d after transplant).


Figure 2
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  		Figure 2. Acute rejection episodes according to study groups were not significantly different at 7 yr after transplantation (P = 0.12).

 
The severity of acute renal allograft rejection was assessed using the Banff 97 classification. There was an NS difference in histologic grade of ACR between the Pred– and the Pred+ groups (Figure 3, Table 3). Treatment of rejection was based on severity, with steroids used for Banff IA and antibody used for any rejection of greater severity (Table 3).


Figure 3
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  		Figure 3. Severity of acute rejection episodes according to study groups and classified with Banff 97 classification.

 

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  		Table 3. Characterization of kidney graft rejection in Pred+ and Pred– groupsa

 
Patients in the Pred– group who experienced their renal allograft rejection and had histologic grade of IA did receive a short course (1 wk) of prednisone taper after the 3-d course of therapy with methylprednisolone. Patients in the Pred– group who experienced renal allograft rejection and had histologic grade greater than IA, after therapy with antibody, were maintained on chronic prednisone at 5 mg/d. During the entire posttransplantation follow-up, 85% of the patients in the Pred– group were maintained off steroids.

Renal Allograft Function
GFR measured at different time points after transplantation using the abbreviated MDRD equation in the Pred+ and Pred– groups is expressed in Figure 4. Both groups lost an average of 0.16 ml/min per 1.73 m2/mo during the 60 mo of follow-up. The slope of GFR decline per month (ml/min per 1.73 m2/mo) was not statistically different even after adjustment for donor age and donor source (P = 0.19 However, at the time of transplantation and throughout the posttransplantation follow-up period, the Pred+ group had a statistically significant lower GFR (–9.9 ± 2.2 ml/min per 1.73 m2; P = 0.0001) than the Pred– group.


Figure 4
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  		Figure 4. Time course of GFR calculated by the Modification of Diet in Renal Disease (MDRD) equation of all kidney transplant patients in the Pred+ and Pred– groups. No significant difference in the slope of GFR was found between study groups (P = 0.19).

 
This difference was no longer significant after analysis of renal allograft function according to the donor source (Figure 5A). As expected, the slope of GFR decline in recipients of living-donor kidneys was not statistically different (P = 0.11; Figure 5A). Both groups lost an average of 0.15 ml/min per 1.73 m2/mo during the 60 mo of follow-up. Recipients of living-donor kidneys, in both groups, had similar GFR at the time of transplantation and throughout the posttransplantation period after adjustment for donor age (P = 0.10).


Figure 5
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  		Figure 5. (A) Time course of GFR calculated by the MDRD equation in transplant recipients of living-donor kidneys in the Pred+ and Pred– groups. No significant difference in the slope of GFR was found between the study groups (P = 0.11). (B) Time course of GFR calculated by the MDRD equation in transplant recipients of deceased-donor kidneys in the Pred+ and Pred– groups. No significant difference in the slope of GFR was found between the study groups (P = 0.81).

 
The slope of GFR decline in recipients of deceased-donor kidneys also was not statistically different (P = 0.81; Figure 5B). Both groups lost an average of 0.18 ml/min per 1.73 m2/mo during the 60 mo of follow-up. The GFR at time of transplantation and throughout the posttransplantation period was significantly different between the Pred+ and the Pred– groups in recipients of deceased-donor kidney (Pred+ group had a GFR that was 12.7 ± 3.6 ml/min per 1.73 m2 less than that of the Pred– group). This difference remained significant even after adjustment for donor age (P = 0.006).

Adverse Events
There were no significant differences between the two groups with respect to infections such as urinary tract infections, pneumonias, CMV, BK nephropathy, and sepsis (Table 4). The rate of malignancy between the two groups was similar. The incidence of hyperlipidemia (total cholesterol >200 mg/dl or LDL >100 mg/dl) was significantly higher in the Pred+ group than in the Pred– group (50 versus 30%; P = 0.001; Table 4). Posttransplantation diabetes was more common in the Pred+ group than in the Pred– group (15 versus 5%; P = 0.001).


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  		Table 4. Adverse events during post-Tx follow-upa

 
Discontinuation or Change of Immunosuppressive Medications
In the Pred+ group, four (4%) patients had modifications of their maintenance immunosuppression. Three of these four patients had tacrolimus stopped during the first 6 mo after transplantation secondary to worsening diabetes and were started on sirolimus. One patient had MMF stopped secondary to severe leukopenia 2 mo after transplantation, and it was substituted with sirolimus.

In the Pred– group, seven (6%) patients had modifications of their maintenance immunosuppression. In four of these seven patients, tacrolimus was stopped and substituted with sirolimus during the first year after transplantation. Reasons for this change were diabetes (n = 2) and severe tremor (n = 2). The remaining three patients had MMF stopped and substituted with sirolimus: Two patients secondary to severe leukopenia and one patient for possible MMF-induced pulmonary fibrosis.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
This study in kidney transplant recipients is the first long-term report with up to 7 yr of data that analyzed, in the current immunosuppressive era, the impact of chronic prednisone versus no prednisone as part of maintenance immunosuppression on graft survival and function and rate/severity of rejection. We have shown that the combination of tacrolimus/MMF in a steroid-free regimen is associated with similar long-term patient and graft survival when compared with the combination of tacrolimus/MMF and prednisone. Both groups had similar rate and severity of acute rejection during the entire posttransplantation follow-up period. Furthermore, the slope of GFR decline during the follow-up time of the two groups of patients who were (Pred+) or were not maintained (Pred–) with prednisone as part of their immunosuppressive regimen was not statistically different. The Pred+ group had a significantly lower GFR than the Pred– group at the time of transplantation and throughout the posttransplantation period. This difference most likely was secondary to the lower number of living-donor kidneys and older age of donors in the Pred+ group than in the Pred– group. In fact, when renal allograft function was analyzed according to the donor source, not only did recipients of living-donor kidneys of both groups have the same decline in GFR over time (–0.15 ml/min per 1.73 m2/mo), but also an NS difference in GFR at the time of transplantation and throughout the posttransplantation period was found between the two groups. We showed that in patients who were maintained on prednisone, the incidence of hyperlipidemia and posttransplantation diabetes was significantly higher then in the Pred– group.

Despite the widely known complications that are associated with prolonged steroid exposure, prednisone utilization in kidney transplant recipients remains widespread. Justification for the continued use of corticosteroids has been based on (1) early reports that steroid withdrawal after transplantation is associated with breakthrough ACR (11–14,22,23,25); (2) the known anti-inflammatory capacity of steroids, leading to the argument that removing prednisone might cause more renal scarring; and (3) the long-term data of Sinclair et al. (15) in which kidney transplant recipients who were randomly assigned at 3 mo after transplantation to steroid withdrawal had a significantly worse graft survival compared with control subjects (73 versus 85%).

We believe that chronic corticosteroid use needs to be reconsidered in the context of new emerging data such as in this report and by examining some of the pitfalls of previous steroid withdrawal studies. For example, although the analysis of Sinclair et al. (15) has the merit to have reported long-term graft survival in a large, prospective, randomized study of patients who were maintained on steroids versus placebo, the maintenance immunosuppression was completely different from the regimens that commonly are used today. In fact, maintenance immunosuppression in many transplant centers now includes at least two drugs: An antiproliferative agent in combination with a calcineurin inhibitor. In Sinclair’s study, all patients simply received CsA monotherapy.

The documented "breakthrough" acute rejection when steroids are tapered rapidly occurs mainly when patients are maintained on prednisone for some period of time after transplantation (2,22). Finally, in the majority of the steroid withdrawal studies, the use of induction agents was not uniform.

It has been reported that with rapid steroid discontinuation or steroid avoidance and with the use of an induction agent at the time of renal transplantation, the incidence of acute rejection is similar to that in patients who are maintained on steroids (24,37). In our study, we confirmed with long-term follow-up that, indeed, the incidence of acute rejection in a rapid steroid elimination is not significantly different from that of patients who receive chronic prednisone as part of their maintenance immunosuppression.

Since the report by Sinclair et al. (15), no randomized, prospective study that has addressed the long-term effects of steroid withdrawal on graft survival and function has been published. Recently, Matas et al. (37) reported their experience with rapid steroid discontinuation on >589 renal transplant recipients with 91 and 84% patient and graft survival, respectively, at 5 yr after transplantation. A merit of this study is the large number of patients and the long-term follow-up. Pitfalls of the study include the lack of a control group receiving prednisone and the lack of analysis on graft function after transplantation.

Our retrospective, sequential, single-center study addresses three important concerns that still persist in the transplant community regarding immunosuppressive protocols with rapid steroid discontinuation: (1) The impact on long-term graft survival, (2) the decline of renal allograft function over time in the absence of prednisone, and (3) risk for ACR that is associated with prednisone-free maintenance regimens. We showed that actuarial graft survival at 7 yr after transplantation and the slope of GFR decline at 5 yr after transplantation are no different in the two groups of transplant recipients (Pred+ and Pred–) analyzed. We also showed that ACR rates and severity are not different between the two groups.

Our study has some limitations. First, this was not a prospective, randomized study. Our analysis was retrospective of two sequential cohorts of renal transplant patients. Although there were no significant differences in the demographic characteristics of the patient groups, the Pred–-treated patients did receive more transplants from living donors and younger donors. To ensure meaningful comparisons, we not only used multivariate analysis but also analyzed renal allograft function according to the donor source, and we demonstrated no difference in slope of GFR between the recipients of living-donor kidneys and deceased-donor kidneys. It is logical that a prospective, randomized trial will need to be implemented to validate our findings.

A second limitation is the lack of renal allograft biopsies to corroborate our conclusions. This important information potentially could have correlated the absence of significant difference in the rate of decline of GFR between Pred+ and Pred– groups at the histologic level. It is intriguing to speculate that because the slope of GFR over the long term posttransplantation follow-up was not different between the two treatment groups, most likely the renal pathology also would have been very similar between the two groups.


   Conclusion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
We have shown that the combination of tacrolimus/MMF using IL-2-RA induction allows for rapid steroid elimination and offers similar outcomes with regard to long-term patient and graft survival, incidence of acute rejection, and graft function when compared with patients who are maintained on long-term prednisone. In our analysis, prednisone avoidance confers important and significant benefits regarding the incidence of hyperlipidemia and posttransplantation diabetes.


   Footnotes
 
Published online ahead of print. Publication date available at www.cjasn.org.

See the related editorial, "Coricosteroids and Kidney Transplantation," on pages 907–908.

Received March 8, 2006. Accepted May 17, 2006.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

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