Mycophenolate mofetil vs azathioprine in a large population of elderly renal transplant patients.

BACKGROUND: Mycophenolate mofetil (MMF) has been shown to decrease acute rejection episodes after kidney transplantation, and has been associated with better graft and patient survival vs azathioprine (AZA). Previous studies reported a higher risk of death due to infection in elderly recipients treated with MMF-based immunosuppression. METHODS: We analysed 5069 elderly ( > 65 years of age) primary renal allograft recipients treated with either MMF or AZA reported to the Scientific Registry of Transplant Recipients between 1988 and 2000, and compared rates of acute rejection, late acute rejection, graft survival, death-censored graft survival, patient survival and death with a functioning graft. RESULTS: In Cox proportional hazard models, MMF was associated with lower rates of late acute rejection with 12 (RR = 0.72, P = 0.11) and 24 months (RR = 0.50, P = 0.028) of continuous therapy. In univariate analysis (Kaplan-Meier), MMF was associated with improved patient (P = 0.0003) and graft (P<0.0001) survival vs AZA, and trends toward improved patient and graft survival in multivariate analyses. CONCLUSIONS: These findings demonstrate the efficacy of MMF-based immunosuppression in elderly transplant recipients and do not suggest an increased risk of death compared to treatment with AZA.     

Mycophenolate mofetil is associated with less death with function than azathioprine in cadaveric renal transplantation.

BACKGROUND: A previous study has argued that mycophenolate mofetil (MMF) is associated with a reduced incidence of death with function when compared to azathioprine (AZA) in cadaveric renal transplantation. This study was designed to verify this result because methodological issues bring these findings into question. METHODS: The data used in this study was derived from records of renal transplants performed in 1995 and 1996 as recorded in the UNOS Scientific Renal Transplant Registry and supplied by the United States Renal Data System (USRDS). Univariate and multivariate survival analysis was used to compare rates of death with function. Covariate characteristics of the donor, recipient, procedures, early outcomes and the transplant centre were considered. RESULTS: 12,251 recipients of cadaveric renal transplants were identified as having received either MMF or AZA, but not both. The relative risk of death with function calculated by the Kaplan-Meier method was 21% less for MMF patients (P=0.005). MMF had from 21% (P=0.008) to 24% (P=0.001) reductions in relative risk by multivariate methods. CONCLUSIONS: The use of MMF is associated with a reduction in the incidence of death with a functioning graft in cadaveric renal transplantation. These results verify previous analyses.     

Mycophenolate mofetil pharmacokinetics in renal transplant recipients on peritoneal dialysis

We prospectively studied the impact of peritoneal dialysis (PD) on the pharmacokinetics of mycophenolic acid (MPA) in five patients following renal transplantation. Three patients had a glomerular filtration rate (GFR) of less than 10 ml/min and two had a GFR of more than 40 ml/min. Pharmacokinetics of MPA and of its main metabolite, mycophenolic acid glucuronide (MPAG), were studied during two consecutive 12-h periods (with and without PD). After initiation of PD in patients with severe renal impairment (GFR < 10 ml/min), MPA-area-under-the-concentration-curve (AUC) decreased up to 59 % and MPAG-AUC decreased up to 26 %. We did not observe any substantial changes in the MPA-AUC or MPAG-AUC of either patient with a GFR above 40 ml/min. Patients with a reduced GFR had much higher MPAG values than patients with a GFR above 40 ml/l; yet, we did not observe any differences in the MPA values. We found a significant inverse correlation between GFR and MPA-AUC (r = 0.81, P < 0.05) and between GFR and MPAG-AUC (r = 0.94, P < 0.01). While MPA was found only in traces in the peritoneal ultrafiltrate, the cumulative amount of MPAG removed by PD reached up to 2 g/12 h, representing 1.2 g of MPA. This is the first report describing a reduction in MPA-AUC and MPAG-AUC during PD. Further studies are needed to completely understand the pharmacokinetics of mycophenolate mofetil during PD. Received: 20 June 1997 Accepted: 26 August 1997     

Safe conversion of mycophenolate mofetil to azathioprine in kidney transplant recipients with sirolimus-based immunosuppression

Aim:   Mycophenolate mofetil (MMF) is a powerful immunosuppressive drug with established efficacy and safety. The long-term use of MMF may bring increased risk of for infection and malignancy and also increased cost of transplantation. The search for minimization of immunosuppressive protocol has led to an open randomized clinical trial of conversion from MMF to azathioprine (AZA).
Methods:   A total of 50 kidney allograft recipients treated with prednisone, sirolimus and MMF were randomized into two groups: converted (AZA group) and continuing (MMF group). The average duration of MMF therapy prior to conversion was 43 months in each group. Inclusion criteria included: patients with serum creatinine levels of less than 200 µmol/L; no past history of acute vascular rejection or recent acute rejection 6 months before randomization; and normal liver function tests.
Results:   Baseline demographics were similar in the two groups. During the 12 month observation period, there were no acute rejection episodes in either group. There were no significant differences in overall patient or graft survival or function. AZA-treated patients had a lower incidence of gastrointestinal complications ( P  = 0.03). Daily cost reduction in the AZA group was more than $US8.79/day per patient.
Conclusion:   In general, replacing MMF with AZA in stable renal transplant recipients is well tolerated and was cost effective with no increased risk of rejection. As the this study was on relatively small samples, larger and longer follow-up studies will be needed to confirm these expected advantages for the long-term outcome and to assess the long-term safety of this minimization of immunosuppressive therapy.     

Increased incidence of allograft rejection in stable heart transplant recipients after late conversion from mycophenolate mofetil to azathioprine.

Mycophenolate mofetil (MMF) is a safe and effective immunosuppressive agent in kidney and liver transplantation. Preliminary studies also support its use in heart transplantation. However, the cost of MMF is substantially greater than azathioprine (AZA), the current alternative. Since the majority of rejection episodes occur within the first few months of transplantation, using MMF early after transplantation and subsequently converting to AZA, after the risk of rejection has diminished, might be cost-effective. In order to evaluate the safety of such a strategy in heart transplant recipients, we reviewed the rejection profiles of a group of patients who were converted from MMF to AZA late after transplantation. Forty-three stable patients on chronic MMF therapy as part of an open-label, long-term safety study were converted to either commercially available MMF (CellCept) or AZA, at the conclusion of the study. Demographic variables, rejection histories before and after conversion, and immunosuppressive regimens were examined. Twenty-three patients were continued on commercial MMF and 20 were converted to AZA therapy. The average duration of MMF therapy prior to conversion was 41 months in each group. Baseline demographics were similar in the two groups. Treated allograft rejection occurred in 10 of 20 patients converting to AZA, as compared to only 1 of 23 patients remaining on MMF; p = 0.002. Additionally, mean scores (1-5 scale) for the three biopsies before and after conversion favored continued MMF therapy (1.5+/-0.6 before and 1.2+/-0.4 after conversion in MMF group vs. 1.3+/-0.5 before and 1.7+/-0.9 after conversion to AZA; p = 0.02). No allograft loss occurred as a result of conversion. These data suggest that conversion from MMF to AZA, even late after transplantation, can be associated with allograft rejection. The costs associated with these rejection episodes (the additional immunosuppressive agents, endomyocardial biopsies, and physician visits) may exceed the potential cost savings of converting stable heart transplant recipients from MMF to AZA.     

Mycophenolate mofetil vs. sirolimus in kidney transplant recipients receiving tacrolimus-based immunosuppressive regimen

Abstract:  Mycophenolate mofetil (MMF) and sirolimus (SRL) are effective immunosuppressive drugs with distinct safety profile.
Methods:  Kidney transplant recipients receiving tacrolimus (TAC)-based immunosuppressive regimen were randomized to receive fixed daily doses of MMF (2 g/d, n = 50) or SRL (one loading dose of 15 mg, 5 mg/d till day 7 and 2 mg/d thereafter, n = 50) without induction therapy.
Results:  No differences were observed in the incidence of the composite (biopsy-confirmed acute rejection, graft loss or death) end-point (18% vs. 16%, p = 1.000), biopsy confirmed acute rejection (12% vs. 14%, p = 1.000), one-yr patient (94% vs. 98%, p = 0.308), graft (92% vs. 98%, p = 0.168), and death-censored graft survival (98% vs. 100%, p = 0.317) comparing patients receiving MMF or SRL respectively. Patients receiving SRL showed worse safety outcomes, higher mean creatinine (1.6 ± 0.5 mg/dL vs. 1.4 ± 0.3 mg/dL, p = 0.007), higher proportion of patients with proteinuria (52.0% vs. 10.7%, p = 0.041), higher mean urinary protein concentrations (0.3 ± 0.5 g/L vs. 0.1 ± 0.2 g/L, p = 0.012), higher mean cholesterol concentration (217 mg/dL vs. 190 mg/dL, p = 0.030), and higher proportion of patients prematurely discontinued from randomized therapy (26% vs. 8%, p = 0.031).
Conclusion:  In patients receiving TAC, MMF produced similar efficacy but superior safety profile compared with SRL.     

Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients

The impact of cytomegalovirus (CMV) infection post-transplantation is in part influenced by the degree of immunosuppression. While mycophenolate mofetil (MMF) does not increase the overall incidence of CMV infection, we have questioned whether or not it increases its severity. Using a case control study design in which 29 renal transplant patients developed CMV disease [17 (59%) of which received azathioprine (AZA) and 12 (41%) received MMF], increases in the frequency of organ involvement with CMV (58 vs. 18%; p = 0.03) and in the number of organs involved with CMV were noted in the MMF versus the AZA group (2.0 vs. 1.0; p = 0.015). These results indicate that the increased immunosuppressive activity of MMF impacts the morbidity of CMV infection, thus warranting the use of effective anti-CMV preventive regimens while patients are treated with MMF.     

Tacrolimus combined with mycophenolate mofetil can effectively reverse C4d-positive steroid-resistant acute rejection in Chinese renal allograft recipients.

BACKGROUND: Tacrolimus (TAC) combined with mycophenolate mofetil (MMF) has been suggested to play a critical role in the reversal of C4d-positive acute humoral rejection (AHR) in renal transplantation, but the efficacy of using only TAC-MMF without immunoadsorption or plasmapheresis has not been investigated. On the other hand, Chinese recipients of renal grafts usually need lower doses of immunosuppressants, and their optimal treatment for acute humoral rejection has not been established. METHODS: Since 1999, we have used TAC-MMF to treat steroid-resistant acute rejection (AR). C4d staining was retrospectively performed in 32 patients with steroid-resistant AR, and the treatments of 19 patients with C4d-positive steroid-resistant AR were investigated. RESULTS: Thirteen of 19 patients received TAC-MMF treatment only; 11 episodes of rejection in them were reversed (7 completely, 4 partially) and only 2 recipients lost their graft. Another 6 patients received immunoadsorption also. One of them failed to respond and lost her graft. Four of 5 patients treated with immunoadsorption and TAC-MMF recovered (3 completely, 1 partially), but 3 of them had severe pneumonia, a complication rate statistically higher than in patients treated with only TAC-MMF (P<0.05). AR occurring during the first two weeks after transplantation had a statistically better outcome than that occurring later (P = 0.003). CONCLUSION: Our study suggests that the combination of TAC and MMF is a potentially safe and economic treatment for most Chinese renal allograft recipients with C4d-positive steroid-resistant AR, especially for rejections developing within the first two weeks after transplantation.     

Mycophenolate mofetil for the prophylaxis of acute GVHD in HLA-mismatched bone marrow transplant patients

Mycophenolate mofetil (MMF), a new immunosuppressive drug successfully used in renal and heart transplant recipients, was used in combination with cyclosporin A (CsA), methotrexate (MTX) and prednisolone for the prophylaxis of acute graft-versus-host disease (aGVHD) after bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) from human leukocyte antigen (HLA)-mismatched, unrelated (n = 9) and related donors (n = 4) in an open single-centre phase II study. Thirteen patients, transplanted from HLA-mismatched donors of 18-57 yr of age, received 1 g MMF daily, starting at day 10, in addition to CsA and prednisolone for aGVHD prophylaxis. All patients were engrafted between days 13 and 15. Four of the 13 patients experienced aGVHD grade I/II (n = 2) and grade III (n = 2). All patients except 3 were alive on day 100 post-transplantation. No severe adverse effects of MMF were recorded. In our pilot study, we demonstrated that MMF can be used safely for the prophylaxis of aGVHD.     

Differential influence of azathioprine and mycophenolate mofetil on the disposition of basiliximab in renal transplant patients

Pharmacokinetic sampling was performed in two multicenter trials in which basiliximab (anti-CD25 monoclonal antibody) was administered with triple immunosuppression consisting of cyclosporine microemulsion, corticosteroids, and either azathioprine or mycophenolate mofetil. Blood samples were collected over 12 wk post-transplant from 31 azathioprine-treated and 66 mycophenolate mofetil-treated patients. Empirical Bayes estimates of each patient's basiliximab disposition parameters were derived and the duration of CD25 saturation was estimated as the time over which serum concentrations exceeded 0.2 microg/mL as confirmed by flow cytometry measurements. Basiliximab clearance was 29+/-14 mL/h when coadministered with azathioprine and 18+/-8 mL/h with mycophenolate mofetil. Both were significantly lower compared with a clearance of 37+/-15 mL/h from a previous study of basiliximab with dual therapy (p<0.001). As a consequence of the lower clearance of basiliximab, the durations of CD25 saturation were prolonged in the presence of azathioprine (50+/-20 d; range, 13--84) and mycophenolate mofetil (59+/-17 d; range, 28--94) compared with dual therapy (36+/-14 d; range, 12--91). A total of 27 acute rejection episodes occurred during the first 6 months in the two studies. Durations of CD25 saturation were not different in these patients compared with those who remained rejection-free in each study. A single patient among 57 who were screened developed anti-idiotype antibodies to basiliximab. The average duration of CD25 saturation was prolonged by 39 and 64% in the presence of azathioprine and mycophenolate mofetil, respectively. This graded effect was also observed for basiliximab clearance and may be due in part to a differentially reduced humoral response to basiliximab. Nonetheless, the range of CD25 saturation durations and basiliximab clearances did not extend outside the range when basiliximab was used with dual therapy in the absence of these agents. Hence, no dosing adjustment is deemed necessary when basiliximab is used in triple immunosuppressive therapy including either azathioprine or mycophenolate mofetil.     

Mycophenolate mofetil, with cyclosporine and prednisone, reduces early rejection while allowing the use of less antilymphocytic agent induction and cyclosporine in renal recipients with delayed graft function

Antilymphocytic agent induction (ALAI), with antithymocyte globulin or monoclonal antibody, is generally used in renal transplantation (TX) to spare renal allografts with poor initial function from the toxic effects of cyclosporine (CsA) and/or to augment immunosuppression (IS) in the patient at a high risk for early rejection. ALAI, unfortunately, increases the cost of TX and the risk to the patient, having been associated with many adverse side effects. An IS protocol, which results in a low incidence of early rejection while using less CsA and ALAI, is a worthwhile goal.
We compare our experience with mycophenolate mofetil (MMF), CsA, and prednisone (MMFCP; n=62) to our azathioprine (AZA), CsA, and prednisone (AZACP; n=50) triple‐drug IS, with and without ALAI. The patient characteristics for age, race, first TX, cadaveric donor, pediatric recipient, and dialysis in the first post‐op week (DGF) were not different for the MMFCP versus AZACP groups. There were more females in the MMFCP group (51.6% versus 30.0%, p=0.022).
We report that rejection‐free survival at 6 months (RF6) was better in the MMFCP versus AZACP group (83.9% versus 60.0%, p=0.005). Less ALAI and CsA were used in the MMFCP patients. At 1 year, actuarial graft survival was 91.9% in the MMFCP group and 81.9% in the AZACP group (p=0.116). Actuarial 1‐year patient survivals were not different in the two patient groups. In the sub‐population of patients with DGF, the RF6 in the MMFCP (n=13) group was 92.3% versus 57.1% in the AZACP (n=14) group (p=0.041). The reduction in early rejection episodes in the patients on MMFCP with DGF was accomplished while using half as much ALAI and lower CsA doses and levels. The African‐American recipient sub‐population on MMFCP also demonstrated an improvement in RF6 while using less ALAI and CsA (78.6% versus 48.0%, p=0.022).
We conclude that the use of MMF‐based triple‐drug IS results in fewer rejection episodes while allowing for lower CsA levels and less ALAI, even in patients with delayed graft function.     

The association between MMF and risk of progressive renal dysfunction and death in adult liver transplant recipients with HCV

Abstract  The impact of a three-drug regimen including mycophenolate mofetil (MMF) vs. a two-drug (no MMF) regimen on progressive renal dysfunction (PRD) in liver transplant recipients with hepatitis C virus (HCV) infection has not been well described. Adults with HCV who received a primary liver transplant between January 1, 2000 and December. 31, 2005 and were discharged from the hospital on a three-drug regimen [CNI+MMF+steroids (S)] (n = 4 946) were compared with those discharged on two-drug regimen (CNI+S) (n = 3 884). Time to PRD (defined by a post-transplant 25% decline in estimated GFR, based on the four-variable MDRD equation) and recipient death were evaluated using Kaplan–Meier analysis. Cox proportional hazards regression was used to estimate the risk for post-transplant PRD and death after controlling for baseline characteristics and extended steroid use. The two groups were similar in baseline characteristics. The percentage of recipients on three- vs. two-drug regimen without PRD was higher, 36.8% vs. 31.9%, (p < 0.001), at three yrs post-transplant; three-drug therapy was associated with a 6% lower adjusted risk of PRD. The death rate and adjusted risk for death was lower for recipients on a three- vs. two-drug regimen. Liver transplant recipients with HCV on a MMF-containing regimen are at a lower risk for PRD and death compared with recipients on a regimen not including MMF.     

Combination therapy with tacrolimus and mycophenolate mofetil: effects of early and late minimization of mycophenolate mofetil after renal transplant

The objectives of the study were: (i) to compare the efficacy and safety of minimizing mycophenolate mofetil (MMF) early (30 d) or late (90 d) after renal transplantation, when used in combination with tacrolimus; (ii) to retrospectively investigate factors associated with early, acute rejections and (iii) to investigate the pharmacokinetic interaction between tacrolimus and diltiazem. A prospective, randomized, multicenter, open-label study was conducted in 124 de novo kidney transplant recipients. Efficacy and safety outcomes were assessed for 180 d after transplantation and subjects were followed-up for a mean duration of 5.1 yr. The efficacy and safety outcomes were comparable whether the dose of MMF was minimized early or late. The incidence of early, acute rejection episodes was higher for recipients who were younger, received a graft from an unrelated donor or failed to achieve adequate tacrolimus concentrations (trough > 10 ng/mL) in the first seven d after transplant. Concomitant use of diltiazem had a tacrolimus-sparing effect in some subjects. Based on these results, we support the achievement of a high target tacrolimus concentration within the first week after renal transplant and suggest that early minimization of MMF can be achieved when used in combination with tacrolimus.     

Single centre experience with mycophenolate mofetil for refractory rejection in cadaveric renal transplantation

Ten patients with refractory rejection following renal transplantation were treated with mycophenolate mofetil (MMF) in an attempt to salvage the allografts. All cases of rejection were biopsy-proven. Seven of the patients had initially been on tacrolimus-based triple therapy and three were on cyclosporin-based regimens. Those on cyclosporin had been unsuccessfully converted to tacrolimus prior to receiving MMF. All patients had received at least one course of methylprednisolone pulse therapy and three had been given OKT3 prior to MMF. MMF was prescribed at a dose of 2000 mg per day in two divided doses and was given in addition to tacrolimus and prednisolone. Eight of the ten patients showed evidence of reversal of rejection, as indicated by improvement in renal function following commencement on MMF, whilst two patients experienced ongoing rejection and underwent graft nephrectomy. One of the patients successfully treated has since had his MMF discontinued due to gastrointestinal intolerance. We conclude that MMF is effective in salvaging renal allografts with resistant rejection and that it has an acceptable side-effect profile. Received: 30 September 1997 Received after revision: 2 December 1997 Accepted: 14 January 1998     

Immunosuppressive efficacy of mycophenolate mofetil when compared with azathioprine and mizoribine against peripheral lymphocytes from renal transplant recipients

Mycophenolate mofetil is currently used instead of azathioprine in clinical transplantation. However, comparative studies for the immunosuppressive potency of anti-metabolites used for organ transplantation have not been well documented. We compared the pharmacological efficacy of mycophenolic acid (MPA), 6-meraputopurine (6-MP), and mizoribine (MZ) for inhibiting purine synthesis of peripheral blood mononuclear cells (PBMCs) in vitro by a mitogen assay procedure. PBMCs were obtained from 18 renal transplant recipients before operation and 18 healthy subjects. The inhibitory efficacy of 6-MP against concanavalin A-induced PBMC blastogenesis exhibited large variations between subjects in both recipients and healthy subjects. In contrast, the pharmacological efficacy of MPA on PBMC blastogenesis showed the smallest inter-individual variation of all the purine synthesis inhibitors examined. Furthermore, the effects of MPA were almost similar in the recipients and healthy subjects. The pharmacological efficacy of MZ against PBMC blastogenesis was weaker than that of the other two agents and the inter-individual variation of MZ IC50 against PBMCs of the patients was larger than that of MZ IC50 against PBMCs of healthy subjects. Reproducible immunosuppressive efficacy of MPA compared with other purinesynthesis inhibitors could be expected from the viewpoint of MPA pharmacodynamics against PBMCs in renal transplantation.     

Preliminary experience with mycophenolate mofetil for preservation of renal function in cardiac transplant patients with documented cyclosporine nephrotoxicity

BACKGROUND: Cyclosporine (CyA) has positively impacted on the outcome of cardiac transplantation; however, the nephrotoxicity associated with CyA has been a major drawback. METHODS: In an effort to reduce exposure to CyA and possibly alleviate its nephrotoxic effects, we undertook a therapeutic strategy to switch cardiac transplant patients with biopsy-proven CyA nephrotoxicity from azathioprine (AZA) to mycophenolate mofetil (MMF) with subsequent CyA dose reduction or elimination. RESULTS: MMF was substituted for AZA in five cardiac transplant patients (four males; mean age, 60 +/- 6 years old; average time from transplant was 7 +/- 3 years) who had biopsy proven evidence of CyA nephrotoxicity, and in whom CyA dose was reduced (3/5) or discontinued (2/5). At the time of the therapeutic intervention, four patients had an average serum creatinine of 230 +/- 62 micromol/L and one patient had just been started on haemodialysis (HD). During an average follow-up period of 42 months, the slope of the inverse serum creatinine significantly improved in three patients and continued to deteriorate in one patient. The patient on HD could be transiently taken off HD. However, he developed a severe episode of cardiac rejection requiring antirejection therapy and increase in the dose of CyA. The patient was subsequently returned back on HD. CONCLUSION: In this preliminary report, we show that AZA to MMF switch with subsequent CyA dose reduction or discontinuation may slow down the progression of kidney disease in some patients. However, the patients should be followed closely for evidence of cardiac rejection.     

Long-Term Use of Mycophenolate Mofetil is Associated With a Reduction in the Incidence and Risk of Late Rejection

To evaluate the association of long-term continuous (minimum 1 year) mycophenolate mofetil (MMF) vs. azathioprine (AZA) therapy with the incidence of late acute rejection, we analyzed 47 693 primary renal allograft recipients reported to the United States Renal Data System between 1988 and 1998. The primary study endpoint was acute rejection beyond 1 year after transplantation. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard models were used to investigate the risk of reaching the study endpoints. All multivariate analyses were corrected for potential confounding covariates. Mycophenolate mofetil was associated with a 65% decreased risk of developing late acute rejection as compared to AZA (RR = 0.35, CI 0.27-0.45, p < 0.001). The incidence of acute rejection episodes at 2 and 3 years post-transplantation was significantly lower in the MMF group (0.9% at 2 years, 1.1% at 3 years) than the AZA group (6.1% at 2 years, 9.3% at 3 years). In the primary vs. repeat late rejection analysis, MMF patients exhibited a decreased late acute rejection risk of 72% (RR = 0.28, p < 0.001) and 60%, respectively (RR = 0.40, p < 0.001). In African Americans, the late acute rejection risk was 70% lower in MMF patients than AZA patients (RR = 0.30, p < 0.001). Further study is indicated to determine the optimal duration of MMF therapy after renal allograft transplantation.     

Randomized trial of early corticosteroid reduction vs. regular‐dose corticosteroid maintenance in combination with tacrolimus and mycophenolate mofetil in living donor kidney transplant recipients: the Brazilian CORRETA trial

Garcia VD, Carvalho DBM, Gonçalves RT, Cavalcanti RL, Campos HH, Abbud‐Filho M, Lobao‐Neto AA. Randomized trial of early corticosteroid reduction vs. regular‐dose corticosteroid maintenance in combination with tacrolimus and mycophenolate mofetil in living donor kidney transplant recipients: the Brazilian CORRETA trial.
Clin Transplant 2010: 24: E109–E115.
© 2009 John Wiley & Sons A/S. Abstract: This multicenter, randomized trial aimed to compare the safety and efficacy of an early reduction in corticosteroid dose vs. long‐term maintenance in Brazilian patients on an immunosuppressive regimen based on tacrolimus and mycophenolate mofetil (MMF). In the control arm, prednisone was progressively reduced from days 8 to 90 and then kept for 12 months. In the experimental arm, prednisone was given for 12 months at the dose of 5 mg every other day. Endpoints were the composite occurrence of death, graft loss, or Banff III acute rejection, and safety. A total of 83 patients were enrolled, and 77 were analyzed for efficacy safety. One death occurred in each group. There were no cases of graft loss and one case of grade 3 acute rejection in the early reduction arm. There was no difference in the rate of the composite primary endpoint between both arms (p = 0.215), and there were no significant differences between both arms in terms of adverse events. Except for higher incidence of hypertriglyceridemia levels among patients in the regular‐dose arm, there were no significant differences between both arms in terms of adverse events. The results of this trial suggest that early reduction of corticosteroid can be feasible and safe within a timeframe of 12 months in patients receiving tacrolimus and MMF.