Impact of dose reductions on efficacy outcome in heart transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil at 12 months post-transplantation

Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.     

Effect of conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium on maximum tolerated dose and gastrointestinal symptoms following kidney transplantation

Despite the potential tolerability advantage of enteric-coated mycophenolate sodium (EC-MPS), no prospective, randomized trial has evaluated whether conversion from mycophenolate mofetil (MMF) to EC-MPS permits mycophenolic acid dose to be increased or gastrointestinal side-effects to be ameliorated. In a randomized, multicenter, open-label trial, kidney transplant recipients experiencing gastrointestinal side-effects either remained on MMF or switched to an equimolar dose of EC-MPS, adjusted 2 weeks subsequently to target the highest tolerated dose up to 1440 mg/day (EC-MPS) or 2000 mg/day (MMF). Patients were followed up to 12 weeks postrandomization. One hundred and thirty-four patients were randomized. The primary efficacy endpoint, the proportion of patients receiving a higher mycophenolic acid (MPA) dose at week 12 than at randomization, was significantly greater in the EC-MPS arm (32/68, 47.1%) than the MMF arm (10/61, 16.4%; P  < 0.001). At the final visit, 50.0% (34/68) of EC-MPS patients were receiving the maximum recommended dose versus 26.2% (16/61) of MMF patients ( P  = 0.007). Kidney transplant patients receiving reduced-dose MMF because of gastrointestinal side-effects can tolerate a significant increase in MPA dose after conversion to EC-MPS. Patient-reported gastrointestinal outcomes with higher doses of EC-MPS remained at least as good as in MMF-treated controls.     

Impact of gastrointestinal-related side effects on mycophenolate mofetil dosing and potential therapeutic strategies

In renal transplant patients receiving mycophenolate mofetil (MMF), maintaining an adequate dosing regimen has been shown to maximize short- and long-term outcomes. Gastrointestinal (GI) adverse events associated with MMF are frequent, and lead to MMF dose reduction or withdrawal in 40-50% of cases. Among MMF-treated patients experiencing GI complications, one analysis has reported MMF discontinuation to be associated with almost a threefold increase in risk of graft loss, while a dose reduction > or = 50% carried over a twofold increase in risk. If GI symptoms improve and the pre-reduction MMF dose is resumed the increased risk of graft loss may be reversed, but continuing intolerance can make this difficult to achieve. Investigation of contributing factors is important and may alleviate symptoms. Conversion to enteric-coated mycophenolate sodium (EC-MPS) may be an effective option. Two open-label studies using patient-reported outcomes data have shown a significant and clinically relevant benefit in GI-related symptom burden after conversion from MMF to EC-MPS. In conclusion, monitoring of GI complications is essential following renal transplantation, and maintaining adequate mycophenolic acid exposure should be a priority when considering treatment options.     

Impact of cyclosporine 2-h level and mycophenolate mofetil dose on clinical outcomes in de novo heart transplant patients receiving anti-thymocyte globulin induction

BACKGROUND: Cyclosporine (CsA) 2-h post-dose level (C2) correlates better than trough levels (C0) with the area under the curve. We evaluated the clinical impact of C2 and mycophenolate mofetil (MMF) dose in adult heart transplant patients receiving anti-thymocyte globulin (ATG) induction. METHODS: Two immunosuppressive strategies were sequentially evaluated. In Group 1 (13 patients), simultaneous C0/C2 (ng/mL) were analyzed. CsA dose monitoring was initially based on C0 : <3 months: 200-300, 4-6 months: 150-250, 6-9 months: 100-200, and on C2 thereafter (as in Group 2). In Group 2 (nine patients), C2 monitoring was implemented: <3 months: 600-800, 4-6 months: 500-700, >6 months: 400-600. All patients received ATG induction, corticosteroids, and MMF (1.0 g b.i.d. in Group 1 and 1.5 g b.i.d. in Group 2). RESULTS: Patients in Group 2 received higher MMF doses during the first trimester. C2 at 1, 3, 6, 12, 24, and 36 months was, respectively, 1199 +/- 476, 1202 +/- 587, 999 +/- 467, 664 +/- 203, 593 +/- 208, and 561 +/- 147 in Group 1, and 809 +/- 160 (p = 0.02), 644 +/- 178 (p = 0.003), 664 +/- 169 (p = 0.02), 616 +/- 221, 464 +/- 234, and 451 +/- 165 in Group 2. The incidence of acute rejection (grade > or =3A) at 6, 12, 24, and 36 months was, respectively, 38.5, 38.5, 46, and 54% in Group 1, and 11, 44, 56, and 56% in Group 2 (p = NS). At 3 months, the creatinine clearance was 25% lower in Group 1. Thereafter, renal function remained stable in both groups. CONCLUSION: Our results suggest that heart transplant patients receiving ATG induction may experience similar outcomes with either a higher C2 and a lower MMF dose or a lower C2 and a higher MMF dose. These results could be considered to design prospective studies to optimize C2 monitoring, to reduce the incidence of acute rejection without increasing the risk of renal dysfunction.     

Elective withdrawal of mycophenolate mofetil in renal transplant recipients treated with mycophenolate mofetil, cyclosporine, and prednisone

In a retrospective study we investigated the risk of acute rejection after the withdrawal of mycophenolate mofetil (MMF) in 39 adult patients treated with cyclosporine (CyA), prednisone, and MMF for at least 6 months following renal transplantation. After reaching a stable renal graft function, MMF was withdrawn and CyA and prednisone were continued. Preceding the withdrawal of MMF, four patients experienced an acute rejection. During a median follow-up of 38 months after discontinuing MMF, no acute rejection occurred. The mean serum creatinine level did not change during the first 6 months after withdrawal of MMF. We conclude that elective withdrawal of MMF in stable renal transplant recipients at 6 months after transplantation bears no important risk of an occurrence of acute rejection. Received: 24 November 1999 Revised: 11 May 2000 Accepted: 18 December 2000     

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     

Clinical outcome of heart transplant recipients receiving tacrolimus with or without mycophenolate mofetil

Tacrolimus (TAC) is a calcineurin inhibitor that is used for cardiac allograft rejection. Efficacy and safety data of a combined TAC/mycophenolate mofetil (MMF) therapy in comparison with a TAC/cortisone therapy in heart recipients are lacking. We analysed the clinical outcome of 41 patients who received TAC in combination with MMF (TMF group) and of 41 patients who received TAC in combination with cortisone (TCO group). Outcomes were serum creatinine levels, cardiac rejections, cytomegalovirus infections, graft vasculopathy, malignancy rates and two-yr survival. Baseline characteristics were comparable in the two study groups. During follow-up, serum creatinine levels decreased slightly in the TMF group (p=0.039) but not in the TCO group. Compared with the TMF group, more clinically proven cardiac rejections which needed a cortisone bolus and more severe rejections that needed lymphoablative therapy with OKT occurred in the TCO group (p=0.001 and 0.04, respectively). In contrast, significantly more cytomegalovirus (CMV) infections occurred in the TMF group compared with the TCO group (p=0.01). The number of patients with graft vasculopathy as well as malignancy rates and overall survival did not differ significantly between the two study groups. The introduction of MMF was associated with an improvement of renal function and a more efficient immunosuppressive therapy. However, this treatment strategy also had led to a higher CMV infection rate compared with cortisone. Consequently, no general recommendation can be given at present whether TAC should be combined with MMF or with cortisone in heart transplant recipients.     

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.     

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.     

Effect of mycophenolate mofetil on hematological side effects incidence in renal transplant recipients

Mycophenolate mofetil (MMF), an immunosuppressant administered after solid organ transplantation, is generally well tolerated; however, it frequently causes hematological toxicity. In this study, we aimed to assess the relation between the pharmacokinetic parameters of MMF metabolites (mycophenolic acid [MPA] and 7‐O‐MPA glucuronide [MPAG]) and the adverse effects on the hematopoietic system in renal transplant recipients. The four‐h pharmacokinetic profiles of MPA and MPAG were determined using the HPLC method for MMF‐treated patients (n = 61) among 106 renal transplant recipients (during the late post‐transplant period) participating in the study. Anemia was more frequently observed in the study group compared with the control group (30.7% vs. 20.0%) and although the difference was insignificant, plasma iron concentrations were significantly higher in patients treated with MMF (32.9 ± 9.4 μmol/L vs. 28.7 ± 9.4 μmol/L; p = 0.032). Iron supplementation was more frequently applied to patients with anemia (48.2%) compared with patients with hemoglobin within the norm (20.3%; p = 0.005). As all MPAG pharmacokinetic parameters correlated negatively with hemoglobin and hematocrit, and MPAG pharmacokinetic parameters were higher in patients with anemia, MPAG may be the predicting factor of MMF side effects. In renal transplant recipients, especially with deteriorated renal function, extensive iron supplementation may be ineffective as anemia was associated with declined renal function and was not caused by low iron concentration.     

Questionnaire-based evaluation of gastrointestinal disorders in de novo renal-transplant patients receiving either mycophenolate mofetil or enteric-coated mycophenolate sodium.

BACKGROUND: Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of our prospective questionnaire-based study was to assess GI side-effects in de novo renal-transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). METHODS: Between January 2002 and April 2003, all patients receiving MPA with a functioning allograft at 1 month post-transplantation were enrolled in this study (n = 130). Ninety-three of them received MMF (group I), and 37 patients received EC-MPS (group II). Each month, every patient completed a questionnaire regarding GI disorders. RESULTS: During the first year post-transplantation, GI disorders occurred in 31 patients from the MMF group (33.3%) and 12 patients from the EC-MPS group (32.4%) (not significant). The incidence of upper GI disorders was also similar in both groups. Diarrhoea was observed in 18 patients (19.3%) from group I, and in five patients from group II (13.5%) (not significant). Its frequency and severity were similar in both groups. Weight loss was observed in three patients receiving MMF. Diarrhoea resolved spontaneously in 10 patients from group I and in all patients from group II. For the other eight patients in group I, the diarrhoea required MMF discontinuation in three patients and dose reduction in five patients. CONCLUSIONS: In conclusion, in this questionnaire-based evaluation, the incidence of GI disorders was similar in patients receiving either MMF or EC-MPS during the first year post-transplantation.     

A critical analysis of racial difference with mycophenolate mofetil (MMF) dosing,clinical outcomes and adverse effects in pediatric kidney transplant patients

Jensen CJ, Shrivastava S, Taber DJ, Weimert NA, Shatat IF, Orak J, Chavin KD, Baliga PK. A critical analysis of racial difference with mycophenolate mofetil (MMF) dosing, clinical outcomes and adverse effects in pediatric kidney transplant patients.
Clin Transplant 2011: 25: 534–540. © 2010 John Wiley & Sons A/S. Abstract: There is paucity in the data examining the differences in mycophenolate mofetil (MMF) dosing and outcomes among pediatric kidney transplant recipients (PKTX) between races. The aims of this study were as follows (i) to assess whether higher doses of MMF are being utilized in African American (AA) PKTX (ii) to determine whether there is a correlation between MMF dose and outcomes between races, and (iii) to assess the adverse effects of MMF between races. This study analyzed 109 PKTX who received MMF between 7/99 and 5/08. Demographics were similar between groups. Fewer AAs received kidneys from living donors (18% vs. 44%), spent more time on dialysis (1.0 vs. 0.5 yr), and had more human leukocyte antigen mismatches (4 vs. 3). MMF doses among AA patients were higher throughout the study, with statistical differences at week 4, month 3, and month 18. AA patients had significantly higher acute rejection rates and trended toward poorer graft survival; infections, adverse events from MMF and post‐transplant lymphoproliferative disease tended to be lower in the AA patients. AA PKTX received higher MMF doses within the first three yr post‐transplant compared to their non‐AA counterparts, yet demonstrate significantly more acute rejection episodes. Importantly, MMF caused fewer adverse events in AA patients, despite these patients receiving higher doses.     

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.     

The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation

BACKGROUND: Mycophenolate mofetil (MMF) has proven to be a very effective drug for the prevention of acute rejection following renal transplantation when dosed as prescribed at 2 or 3 g/d. However, circumstances arise in clinical transplantation where the dose must be lowered, either to avoid drug toxicity or because of concurrent infection. The impact on the incidence of acute rejection and graft survival when the MMF dose must be lowered has not previously been investigated. METHODS: In this study, a cohort of 721 kidney transplant recipients who received immunosuppression using MMF in conjunction with cyclosporine and prednisone and OKT3 (n = 425) or Simulect (n = 296) induction were evaluated. Clinical outcomes were compared and contrasted between patients with and without MMF dose changes within the first year post-transplantation. RESULTS: The majority of patients (70.3%, n = 507) had at least one dose change within the first post-transplant year. Compared with the 214 patients who did not have a dose change, these patients had a much higher incidence of acute rejection within the first post-transplant year (23.3% vs. 3.7%, p < 0.001). This resulted in a significantly decreased 3-yr death-censored graft survival (76.3% vs. 88.3%, p = 0.003). The incidence of acute rejection for patients who had a dose change was highest if the dose change occurred within the first post-transplant month (34.4%). The incidence of acute rejection for the dose change patients was influenced by recipient ethnicity (African-American vs. Caucasian) and the type of induction agent used (OKT3 vs. Simulect). CONCLUSION: Altering the dose of MMF within the first post-transplant year correlated with a significantly worse clinical outcome in this cohort of renal transplant recipients. These data suggest that avoidance of MMF dose changes within the first year after renal transplantation would result in improved graft survival.     

Improvement in long-term graft survival in cadaveric renal transplant recipients treated with mycophenolate mofetil

Though mycophenolate mofetil has markedly reduced the incidence of acute rejection in renal transplantation, a significant improvement in graft survival has been more difficult to demonstrate. This retrospective study compares an historical control group of 210 consecutive renal transplant patients, who had received ATG induction associated with cyclosporin, prednisolone and azathioprine, with 187 patients receiving mycophenolate instead of azathioprine. The incidence of acute rejection was decreased with mycophenolate. In rejection-free patients, the 3-year graft survival rates were equivalent. In contrast, graft survival at 3 years improved significantly for patients who experienced a rejection crisis and remained under the initial triple drug regimen with mycophenolate compared to the patients of the historical group who were kept on azathioprine after a rejection episode. In conclusion, mycophenolate mofetil is not only able to reduce the incidence of acute rejection but could also improve the prognostic significance of acute rejection crises.     

Improvement of gastrointestinal symptoms after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients

As many as 50% of liver transplant patients suffer gastrointestinal (GI) disturbances post-transplant. Conversion from mycophenolate mofetil (MMF) to mycophenolate sodium (EC-MPS) alleviates GI symptom burden in renal transplant recipients. We employed a validated patient and physician-reported assessment to evaluate the impact of conversion to EC-MPS in liver transplant patients. This is a prospective, longitudinal, single-center, open-label pilot study. Thirty-one MMF-treated liver transplant patients with GI symptoms were converted to equimolar EC-MPS. Gastrointestinal Symptom Rating Scale (GSRS), GI Quality of Life, SF-12v2 and physician-reported assessments were used to evaluate GI symptom burden and severity. A significant improvement in overall GSRS score was noted from baseline (2.57; 95% CI 2.12-3.10) to one month (1.90; 1.68-2.12; p = 0.0007) and three months (1.82; 1.60-2.04; p = 0.0002) post-conversion with significant reductions in all subgroups except Reflux. The overall Gastrointestinal Quality of Life Index (GIQLI) score also showed significant increase in health-related quality of life between one month (90.89; 84.04-97.75) and three months (100.04; 94.57-105.51; p = 0.0009), with all subgroups except social functioning (p = 0.0861) and medical treatment (p = 0.3156) demonstrating significant improvements. This pilot study demonstrates improvement in GI symptom burden when converting from equimolar doses of MMF to EC-MPS. This benefit persisted for three months without evidence of rejection.     

吗替麦考酚酯与麦考酚钠肠溶片对肾移植受体血药浓度的影响

目的  探讨吗替麦考酚酯（MMF）与麦考酚钠肠溶片（EC-MPS）在同等生物效应剂量下对肾移植受体麦考酚酸（MPA）血药浓度和不良反应的影响。方法  回顾性分析106例活体供肾移植受体的临床资料。按肾移植术后服用不同药物分为两组,MMF组（M1组,62例）和EC-MPS组（M2组,44例）。两组受体的免疫抑制方案分别为M1组用他克莫司（FK506）+MMF+泼尼松,M2组用FK506+EC-MPS+泼尼松。分析两组受体服药后1、2、3周和1、2、3个月MPA血药浓度的变化情况、不良反应发生情况及服用药物所花费用。结果  采取同等生物效应给药,服药后第1、2、3周,第1、2、3个月时M1组MPA血药谷浓度比M2组低,各个时间点两组间比较,差异均有统计学意义（均为P < 0.05）。与M1组比较,M2组术后不良反应的发生率较低且症状较轻。采用同等生物学效应给药,M1组服用MMF所花费用1 710元/月,M2组服用EC-MPS所花费用2 736元/月,但M1组因治疗药物不良反应所产生费用远高于M2组。结论  同等的生物效应剂量下服用EC-MPS的患者相对服用MMF的患者能维持更高的MPA血药浓度并且不良反应更少。     

The use of daclizumab as induction therapy in combination with tacrolimus and mycophenolate mofetil in recipients with previous transplants

Clinical trials using daclizumab as induction therapy in combination with tacrolimus (TAC) and mycophenolate mofetil (MMF) have been shown to reduce the incidence of acute rejection episodes in solid organ transplantation. In an attempt to obtain a low rejection rate we proceeded with the use of daclizumab as induction therapy, in combination with TAC and MMF for recipients with previous transplants. In this study, we analyzed patients who received previous transplants, treated with the above immunosuppressive regimen. Group A consisted of four patients with previous liver transplants, group B consisted of 16 recipients with previous kidney transplants and group C consisted of three patients with previous simultaneous pancreas-kidney transplants. All patients underwent cadaveric kidney transplants except one patient in group B, who underwent a pancreas transplant. At 12 months, patient and graft survival for all groups was 100 and 100%, respectively. Acute rejection rate was 0% for group A, 12.5% for group B, and 0% for group C. Daclizumab induction therapy is effective for patients with previous transplants and does not appear to increase the risk of acute rejection.     

Impact of mycophenolate mofetil on recurrent rejection in kidney transplant patients

PURPOSE: Mycophenolate mofetil (MMF) has emerged as a valuable adjunctive agent in renal transplantation. However, due to intolerable adverse effects associated with MMF use in our transplant population, we have used MMF selectively in patients at high risk for recurrent graft rejection, since these patients are known to be at risk for poor long-term graft outcomes. The purpose of this study was to assess the efficacy of MMF in preventing the recurrence of acute rejection following an initial rejection episode in kidney transplant patients in the first year following transplantation. METHODS: Forty-four kidney transplant recipients were given MMF prospectively following treatment of their initial rejection episode to prevent recurrent rejection. MMF 1-2 g/d was given. Doses were adjusted based on tolerance; MMF therapy was to be continued for at least 6 months. The control group consisted of 124 consecutive kidney transplant recipients who had received standard anti-rejection therapy without the addition of MMF. Maintenance immunosuppression consisted predominantly of cyclosporine, prednisone+/-azathioprine. Anti-rejection therapy for both groups consisted of either corticosteroids (methylprednisolone 500 mg i.v. for 3 d or oral prednisone 2 mg/kg/d with rapid taper over 3 wk), OKT3 5 mg/d for 10 d or ATG 15 mg/kg/d for 10 d. All rejection episodes were confirmed by biopsy. RESULTS: The majority of rejection episodes were characterized histologically as mild or moderate. Most patients (76%) received corticosteroids for treatment of their first rejection episode. There was a 68% reduction in the incidence of recurrent rejection episodes within the first year of transplant in patients receiving MMF; only 14% of recipients receiving MMF developed recurrent rejection compared to 44% of patients in the control group (p<0.05). Approximately 50% of patients developed MMF-associated adverse effects (leukopenia, GI toxicity). Only 52% of patients remained on MMF at 6 months. One-yr graft survival was 86% in the MMF group and 89% in the control group (p>0.05). One-year patient survival was 93 and 100%, respectively (p>0.05). CONCLUSIONS: The addition of MMF to maintenance therapy for patients experiencing acute renal allograft rejection may prevent recurrent rejection episodes in the subsequent follow-up year.