Long‐term outcomes in African American kidney transplant recipients under contemporary immunosuppression: a four‐yr analysis of the Mycophenolic acid Observational REnal transplant (MORE) study

Mycophenolic acid Observational REnal transplant (MORE) was a prospective, observational study of de novo kidney transplant patients receiving mycophenolic acid (MPA). Four‐yr data on 904 patients receiving tacrolimus and enteric‐coated mycophenolate sodium (EC‐MPS) or mycophenolate mofetil (MMF) were analyzed to evaluate immunosuppression and graft outcomes in African American (AA, n = 218) vs. non‐AA (n = 686) patients. Mean tacrolimus dose was higher in AA vs. non‐AA patients but mean tacrolimus trough concentration was similar. Use of the recommended MPA dose in AA patients decreased from 78.9% at baseline to 33.1% at year 3. More AA patients received the recommended MPA dose with EC‐MPS than MMF at month 6 (56.2% vs. 35.7%, p = 0.016) and month 36 (46.6% vs. 16.7%, p = 0.029), with no safety penalty. Significantly, more AA patients received corticosteroids than non‐AA patients. Biopsy‐proven acute rejection was higher in AA vs. non‐AA patients (18.9% vs. 10.7%, p = 0.003), as was graft loss (10.9% vs. 4.4%, p = 0.003); differences were confirmed by Cox regression analysis. Patient survival was similar. Estimated GFR was comparable in AA vs. non‐AA patients. Kidney allograft survival remains lower for AA vs. non‐AA recipients even under the current standard of care.     

Long‐term dosing patterns of enteric‐coated mycophenolate sodium or mycophenolate mofetil with tacrolimus after renal transplantation

MORE was a four‐yr, prospective, observational study at 40 transplant centers in the US. Data were analyzed to evaluate changes in mycophenolic acid (MPA) dosing over time in 904 de novo kidney transplant recipients receiving enteric‐coated mycophenolate sodium (EC‐MPS, n = 616) or mycophenolate mofetil (MMF, n = 288) with tacrolimus. Induction therapy and steroid treatment were similar in the two subpopulations. The proportion of patients receiving the maximal recommended MPA dose was 80.5%, 43.9%, 39.2%, 34.6%, and 30.1% at baseline and years 1, 2, 3, and 4, respectively. More patients received the maximal recommended MPA dose with EC‐MPS vs. MMF at month 1 (79.2% vs. 71.7%, p = 0.016), month 3 (68.5% vs. 56.9%, p = 0.001), and month 6 (52.9% vs. 44.0%, p = 0.028). Multivariate analysis showed the risk of biopsy‐proven acute rejection, graft loss or death to be similar for EC‐MPS vs. MMF. Estimated glomerular filtration rate (GFR) was similar with EC‐MPS vs. MMF at all time points. There were no significant differences in any category of adverse event between the EC‐MPS and MMF cohorts during follow‐up, including gastrointestinal events. In conclusion, MPA dose was maintained more effectively in the first six months after kidney transplantation using EC‐MPS vs. MMF, without an increase in adverse events.     

The renal benefit of mycophenolate mofetil after liver transplantation

Haywood S, Abecassis M, Levitsky J. The renal benefit of mycophenolate mofetil after liver transplantation.
Clin Transplant 2011: 25: E88–E95. © 2010 John Wiley & Sons A/S. Abstract: Background: The risk and benefit of adding mycophenolate mofetil (MMF) to a standard immunosuppressive regimen at the time of liver transplantation (LT) is not well described. Methods: We performed a retrospective case–control analysis comparing one‐yr outcomes of all LT recipients at our institution treated with post‐operative tacrolimus (TAC), MMF, and steroids vs. TAC and steroids. Results: A total of 101 LT recipients (50:51 case:control) were analyzed. Despite more renal dysfunction at LT, the MMF + TAC group had similar serum creatinine (Cr) and glomerular filtration rate (GFR) as the TAC group one‐yr post‐LT. In this time period, Cr decreased (1.57–1.22 mg/dL, p = 0.04) and GFR increased (57.5–65.1 mL/min per 1.73 m², p = 0.05) in the MMF + TAC group, while Cr increased (1.11–1.35, p < 0.01) and GFR declined (73.5–60.1, p < 0.001) in the TAC group. These findings occurred without a difference in absolute rejection episodes, hospitalizations, infections, deaths, or time to above events (p > 0.05). Subgroup analysis of patients stratified by pre‐transplant renal dysfunction (Cr ≥ 1.2 mg/dL) supported the previous. MMF was reasonably well tolerated with a low rate of discontinuation. Conclusions: The use of adjunctive MMF immediately after LT may protect against calcineurin inhibitor nephrotoxicity, potentially without the need for dose reduction or increased risk of adverse events.     

Pharmacokinetics of daclizumab and mycophenolate mofetil with cyclosporine and steroids in renal transplantation

Daclizumab and mycophenolate mofetil (MMF) decrease the incidence of acute allograft rejection. This double-blind, randomized, placebo-controlled trial was performed primarily to assess the pharmacokinetics of MMF in an immunosuppressive regimen incorporating daclizumab. At five centers, 75 renal transplant recipients were randomized 2:1 to receive either daclizumab 1 mg/kg or placebo pre-transplantation and every other week, for a total of five doses. All patients received cyclosporine, steroids, and MMF. Levels of mycophenolic acid (MPA), its glucuronide metabolite, and daclizumab were measured after dosing on days 28 and 56. Safety parameters evaluated included: adverse events, laboratory abnormalities, infections, patient/graft survival, incidence of lymphoproliferative disorders, and incidence of acute rejection at 12 months. The concomitant administration of daclizumab and MMF had no effect on the pharmacokinetics of MPA: AUC(0-8) values (microg h/mL +/- SD) on day 28 were 30.1 +/- 13.3 for daclizumab-treat patients vs. 31.1 +/- 12.4 for placebo and on day 56, 37.7 +/- 18.2 for daclizumab-treated patients vs. 35.7 +/- 14.0 for placebo. Adverse events were similar between the two groups. Acute rejection at 12 months occurred in 14% of patients receiving daclizumab and 20% of patients receiving placebo. The coadministration of daclizumab did not result in a pharmacokinetic interaction with MPA, the active metabolite of MMF.     

Equivalent Pharmacokinetics of Mycophenolate Mofetil in African-American and Caucasian Male and Female Stable Renal Allograft Recipients

African-American (AA) renal transplant recipients require higher doses of mycophenolate mofetil (MMF) than Caucasians. A hypothesized pharmacokinetic (PK) difference was tested in stable renal transplant recipients. Whole blood was collected before, and 20, 40 and 75 min, and 2, 3, 4, 6, 8 and 12 h after the MMF dose. Mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) were analyzed using HPLC. Analysis of variance was performed for the primary end-points of dose-adjusted PK parameters AUC0-12 and Cmax of MPA using log-transformed values. Differences between races and genders were estimated: 90% confidence intervals (CI) were calculated. Back-transformation gave estimates of the race and gender ratio and their CI. Equivalence of the groups was determined if the 90% confidence limits were included in the interval (0.80, 1.25). The calculated PK parameters were comparable among the four subgroups (Caucasian, AA, Male, Female). The 90% CIs for the ratio of dose-adjusted AUC0-12 of MPA between races were between 89.7 and 112.9%. There were no race, gender or race-by-gender effects (p-values = 0.196) nor differences between diabetics and nondiabetics. This study demonstrates that dosing requirement for MMF in AA and Caucasians is unlikely to be related to different exposures to MPA.     

Calcineurin inhibitor withdrawal and conversion to mycophenolate mofetil and steroids in cardiac transplant recipients with chronic renal failure: a word of caution

Abstract: Background: Chronic renal failure (CRF) is a common complication of calcineurin inhibitor (CNI)‐based immunosuppression following cardiac transplantation (HTx). The aim of this prospective study was to evaluate the impact of an immunosuppressive conversion from CNIs to mycophenolate mofetil (MMF) and steroids in cardiac transplant recipients with CRF on renal and cardiac graft function. Methods: Since 1999, 12 HTx recipients (10 men; 58 ± 3.6 yr of age; 8.7 ± 4.2 yr after HTx) with CNI‐based immunosuppression and a calculated creatinine clearance (CreaCl) <50 mL/min were included. Most patients (10/12) were on cyclosporine and two patients were on tacrolimus prior inclusion. MMF was started with 0.5 g/d and adjusted according to the target trough levels (2–4 ng/mL). Prednisone dosage was 0.4 mg/kg. Subsequently, CNIs were completely withdrawn. Acute rejection episodes were excluded one and three months after conversion by endomyocardial biopsy and by echocardiography every three months thereafter. Results: After a mean follow‐up of 20 ± 16 months, CreaCl improved significantly: pre‐conversion vs. post‐conversion: 32.8 ± 12.2 mg/dL vs. 42.8 ± 21.14 mg/dL, p = 0.03. However, four acute rejection episodes occurred and patients were reconverted to CNIs. Additionally, six patients had a new onset of graft vessel disease (GVD) one yr after conversion. As a result of these adverse events, the study was stopped after inclusion of only 12 of the scheduled 30 patients. Conclusions: Conversion to MMF and steroids after HTx improves renal function, but increases the risk for recurrent rejection and GVD. Therefore, MMF and steroids should only be considered in patients with a markedly low risk for rejection.     

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.     

Renal transplant patients with gastrointestinal intolerability to mycophenolate mofetil: conversion to enteric-coated mycophenolate sodium

The introduction of mycophenolate mofetil (MMF) was an important advance in immunosuppressive therapy, although its use is limited by adverse gastrointestinal events. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) has been developed to avoid these side effects. Recent clinical trials have demonstrated that EC-MPS is a safe drug in both de novo and maintenance renal transplant patients. In this prospective study, therapeutically equivalent doses of EC-MPS were administered to 39 stable kidney transplant patients receiving MMF. After 3 months of treatment with EC-MPS the incidence of adverse gastrointestinal events was lower (15.8% of the patients). There were higher levels of mycophenolic acid after conversion to EC-MPS, probably due to better absorption. These factors allowed decreased doses and levels of calcineurin inhibitors without increasing the risk of graft rejection. At 3 months postconversion, serum creatinine improved from the mean baseline value of 1.83 +/- 0.12 mg/dL to 1.70 +/- 0.10 mg/dL. In conclusion, EC-MPS was well tolerated in maintenance renal transplant patients with adverse gastrointestinal events secondary to MMF.     

Mycophenolic acid levels in pediatric heart transplant recipients receiving mycophenolate mofetil.

BACKGROUND: Mycophenolate mofetil (MMF) is an immunosuppressive agent that has shown promise in adult patients who have undergone heart transplantation. There have been a number of studies of the pharmacokinetics of MMF in adult solid organ transplant recipients, but there is very little information in the pediatric population. The purpose of this study was to review our experience with MMF dosing and the role of mycophenolic acid (MPA) levels for therapeutic drug monitoring in a population of pediatric heart transplant recipients. METHODS: Data were obtained by review of the pediatric heart transplant database between November 1, 1997 and October 15, 1998. The data included all serum trough MPA levels, patient age, weight, height, indication for and dose of MMF, other medications, and details of all episodes of graft rejection. RESULTS: Forty-four patients (27 males) had a total of 128 serum trough MPA levels. Median age at transplant was 2.7 years (7 days to 18.4 years), and at time of review was 6.3 years (29 days to 23.5 years). MMF treatment was used for induction in 18 patients, induction and rejection in 23 patients and graft vasculopathy in 3 patients. Dosing by body surface area (mg/m(2)), age and interval from transplantation were all independently associated with MPA level. There was a trend toward requiring higher doses to achieve desired levels (>3 ng/ml) in younger patients. The average dose to achieve desired levels was higher in the immediate post-transplant period. There was a trend that MPA levels for a given dose were higher in patients on concurrent tacrolimus therapy. CONCLUSIONS: (1) There is marked individual variation in pharmacokinetics of MMF in pediatric patients; (2) dosing by body surface area may be advantageous; (3) higher MMF doses may be required at younger ages and in the early period after transplantation; (4) lower MMF doses may be required with concurrent tacrolimus therapy; and (5) serum trough MPA levels may relate to efficacy. Therefore, therapeutic drug monitoring of serum trough MPA levels may be required for individualized MMF dosing in pediatric cases.     

Conversion to sirolimus in pediatric renal transplantation recipients

We retrospectively evaluated the efficacy and safety of sirolimus (SRL) in 16 pediatric renal transplant recipients, who were 9.4 +/- 4.1 years of age when they first received SRL. The indications for SRL therapy were rescue from steroid-resistant acute rejection (31.3%), neoplasia (31.3%), diabetes (12.5%), polyomavirus-associated nephropathy (6.3%), chronic allograft dysfunction (6.3%), calcineurin inhibitor nephrotoxicity (6.3%), and hemolytic uremic syndrome (6.3%). Mean follow-up after the switch to SRL was 17.7 +/- 15 months. The final immunosuppression was CNI + SRL + prednisone (PRED) in five patients, SRL + PRED in six, SRL + mycophenolate mofetil (MMF) + PRED in four, and SRL + MMF in one. The use of SRL in these selected pediatric renal recipients was successful, except when creatinine was high at the moment of conversion. Further studies are necessary to assess the beneficial outcomes versus adverse events among the pediatric transplant population receiving SRL for immunosuppression.     

Enteric-coated mycophenolate sodium immunosuppression in renal transplant patients: efficacy and dosing

Mycophenolate mofetil (MMF), a mycophenolic acid (MPA) formulation, has improved both short- and long-term outcomes following renal transplantation, but is often associated with gastrointestinal (GI) complications that can lead to dose reduction or discontinuation, potentially jeopardizing patient outcomes. Enteric-coated mycophenolate sodium (EC-MPS) delivers equivalent MPA exposure to MMF and offers the potential to reduce GI burden (while maintaining patient safety). Here we review the efficacy of EC-MPS compared with MMF in renal transplant patients in terms of biopsy-proven acute rejection and graft loss, and examine the use of EC-MPS in newer regimens such as intensified dosing and calcineurin inhibitor minimization.     

Inferior late functional and metabolic outcomes in African American simultaneous kidney-pancreas recipients

The aim of this study was to determine the impact of ethnicity on the major endpoints of a prospective, multi-center, randomized trial of 2 dosing regimens of daclizumab compared with no antibody induction in simultaneous kidney-pancreas transplantation (SKPT). A total of 298 patients were randomized into 3 groups: daclizumab 1 mg/kg/dose every 14 days for 5 doses (Group I, n = 107), daclizumab 2 mg/kg/dose every 14 days for 2 doses (Group II, n = 113), and no antibody induction (Group III, n = 78). All patients received tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. Thirty-seven patients (12.4%) were African American (AA) and 261 were non-African American (NAA). Demographic and transplant characteristics were comparable between AA and NAA patients. At 3 years, there were no differences in patient, kidney, or pancreas graft survival rates. Rejection rate was similar between AA and NAA. Although mean serum creatinine (SCr) levels at 1 year were comparable between AA and NAA patients (AA 1.5 mg/dL vs NAA 1.3 mg/dL; P = .23), by 3 years AA patients had higher mean SCr levels (AA 2.1 mg/dL vs NAA 1.5 mg/dL; P < .0001) and lower calculated glomerular filtration rate (GFR) (AA 45 mL/min vs NAA 56 mL/min; P = .01). Mean HgbA1C, total cholesterol, and diastolic blood pressure (BP) were higher in AA patients at 3 years, compared with NAA patients. In conclusion, in this study, AA patients had worse late functional and metabolic outcomes after SKPT compared with NAA patients. Further longitudinal follow-up is needed to determine the ultimate impact of these findings on long-term patient and graft survival.     

Levels of mycophenolic acid and its glucuronide derivative in the plasma of liver, small bowel and kidney transplant patients receiving tacrolimus and cellcept combination therapy

In order to help assess the usefulness of mycophenolate mofetil (MMF) as an immunosuppressive agent in recipients of organs other than kidneys, we measured the trough levels of the active metabolite of MMF, mycophenolic acid (MPA), and its inactive glucuronide derivative (MPAG), in the plasma of liver (n = 83) and small bowel transplant patients (n = 15) receiving MMF in combination with tacrolimus. These levels were compared with a group of renal transplant patients (n = 25) receiving the same drug regimen. All patient groups were otherwise comparable except the small bowel patient group which contained more pediatric patients (average age 18.7 +/- 3.9 years), and, therefore, received a higher average drug dose (in mg/kg). Despite this, these patients displayed the lowest levels of MPA of any group (0.39 +/- 0.08 microg/ml, P < 0.001 vs. 1.10 +/- 0.17 microg/ml for liver transplant patients, P < 0.001 or 2.46 +/- 0.37 microg/ml for renal transplant patients, P < 0.001). There were no statistically significant differences in MPAG levels between any of the groups. Although preliminary, these data demonstrate significant transplanted organ-specific differences in MMF pharmacology and/or bioavailability, and suggest the need for separate evaluation of MMF dosing for each transplant type.     

The Use of Daclizumab, Tacrolimus and Mycophenolate Mofetil in African-American and Hispanic First Renal Transplant Recipients

Limited data are available on the use of tacrolimus and mycophenolate mofetil in conjunction with anti-IL-2 receptor antibody, in groups of kidney transplant recipients considered to be at higher risk. This study compared the incidence of acute rejection between African-American (AA), Hispanic (H), and non-African-American, non-Hispanics (non-AA, non-H) first renal transplant recipients. We studied 233 sequential first renal transplants. Of the 233, 37 recipients (16%) were AA, 85 (36.5%) were H and 111 (47.5%) were non-AA, non-H. All received daclizumab induction therapy (1 mg/kg) on the day of surgery, and every other week for a total of 5 doses, as well as mycophenolate mofetil, tacrolimus, and steroids. At 1 year, patient and graft survival were 97% and 95% in AA, 98% and 98% in H, and 96% and 95% in non-AA, non-H, respectively (not statistically different). Biopsy-proven acute rejection episodes were 8.1% in AA, 4.7% in H, and 4.5% in non-AA, non-H (also not statistically different). This immunosuppressive protocol appears to be safe and effective in helping to minimize biopsy-proven acute rejection and optimize renal allograft survival in African-American and Hispanic renal transplant recipients in the first year post transplantation.     

The effect of Daclizumab in a high-risk renal transplant population

INTRODUCTION: African-American (AA) renal transplant recipients have a higher incidence of acute rejection when compared to Caucasian renal transplant recipients. This higher rejection rate holds true even with the addition of several of the newer immunosuppressive agents (e.g. mycophenolate mofetil (MMF) and Rapamycin). Acute rejection rates among Hispanic (H) renal transplant recipients are higher in some settings, while lower or the same as in Caucasians in other settings. IL-2 receptor antibodies have been shown to decrease rejection rates when added to a regimen of cyclosporine (CsA), azathioprine and prednisone. Limited data are available on these agents in conjunction with triple CsA, MMF and prednisone therapy, particularly in higher risk group patients. We studied the effect of the addition of the IL-2 receptor antibody Daclizumab to a CsA, MMF, prednisone regimen in a group of African American and high-risk Hispanic renal transplant recipients. METHODS: This was a non-randomized, prospective study. A total of 49 renal transplant recipients (29 African American and 20 Hispanic) were studied and followed. A simultaneous cohort of 56 (31 African-American and 25 Hispanic) renal transplant recipients receiving CsA, MMF and prednisone with no standard induction agent served as the control group. The study cohort received the same regimen with the addition of Daclizumab at 1 mg/kg for five doses over 10 wk. Multivariate analysis was performed to isolate independent factors influencing the study's results. RESULTS: A total of 56 patients in the control group and 49 patients in the Daclizumab group received an average follow-up of 17.1 +/- 6.9 and 12.7 +/- 5.1 months, respectively. Acute rejection rates were lower in the Daclizumab group as compared to the control group 26.4% versus 49.3% per patient years, respectively. A total of eight recurrent rejections in 6 patients occurred in the control group and none in the Daclizumab arm. Graft loss at this follow-up was no different between the groups. CONCLUSION: The addition of Daclizumab to a regimen of CsA, MMF and prednisone decreases acute rejection episodes in a high-risk group of African American and Hispanic renal transplant recipients.     

Safety assessment of the conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable renal transplant recipients

The immunosuppressant mycophenolate mofetil (MMF; CellCept) has greatly improved transplant recipients' clinical outcomes, but its efficacy may be limited by dose adjustments due to adverse events (AEs). An enteric-coated formulation of mycophenolate sodium (EC-MPS; myfortic), designed to improve gastrointestinal tolerability is now available. This Latin-American, prospective, multicenter, open-label, 6-month trial assessed the safety and tolerability of converting renal transplant recipients from MMF to EC-MPS. In total, 237 renal transplant recipients (stable > or = 3 months' posttransplant) receiving MMF (< or =1000 mg b.i.d.) were enrolled. Adults (n = 218) were converted to EC-MPS 720 mg b.i.d. (equimolar to MMF 1000 mg b.i.d.) even if they were initially receiving <1000 mg MMF b.i.d. (ie, 47 adults received a higher than equimolar dose of EC-MPS). Children (n = 19) were converted to EC-MPS 450 or 432 mg/m2 b.i.d. Patients also received cyclosporine microemulsion (Neoral) and corticosteroids. There were three acute rejections and no graft failures. The incidence of AEs was 59.9% (in those receiving a higher than equimolar EC-MPS dose it was 57.4%). In all, 22% of patients had gastrointestinal AEs, 37% had infections, and 4.8% had hematological AEs. Only 24 patients (10%) had an AE-related dose reduction. Seven of these patients had received higher than equimolar doses of EC-MPS. Patients can be safely converted from different doses of MMF to a standard dose of EC-MPS. The requirement for EC-MPS dose reduction to manage AEs was relatively low. Use of EC-MPS is a valid alternative for renal transplant recipients receiving maintenance MMF treatment.     

Outcomes of simultaneous kidney-pancreas transplantation in African-American recipients: a case-control study

INTRODUCTION: Previous studies have suggested that African-American (AA) ethnicity is a risk factor for rejection and graft loss after kidney transplantation. However, little data is available regarding outcomes after simultaneous kidney pancreas transplantation (SKPT) in AA recipients. The objective of this study was to compare the outcomes of SKPT in AA patients to matched Caucasian patients as controls. METHODS: From January 1996 to September 1999, we performed 79 SKPTs, including 10 in AA recipients. Ten Caucasian controls were selected and matched for age, gender, weight, timing and technique of transplantation, and immunosuppressive regimen. Clinical outcomes were collected and compared between the two groups. RESULTS: The two groups were well matched for donor and recipient demographic, immunologic and transplant characteristics, including 2 patients in each group with type 2 diabetes. All patients received tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids, and about half in each group received antibody induction therapy. Patient survival was 100% in both groups with a mean follow-up of 18 months (range 6 47). Kidney and pancreas graft survival rates were both 80% in the AA and 100% in the Caucasian groups, respectively (p = 0.14). All but one kidney (in the AA group) and all pancreas grafts experienced immediate function. There were two immunologic kidney and two immunologic pancreas graft losses in the AA group. No grafts were lost due to technical problems. The mean length of initial hospital stay was 16 d in the AA group compared to 10 d in the Caucasian group (p = 0.07). The AA group had a slight increase in the number of readmissions (mean 2.2 AA vs. 1.6 Caucasian, p = 0.08). The incidence of biopsy-proven pancreas acute rejection was significantly higher in the AA group (50%) compared to the Caucasian group (10%) (p = 0.05). The incidence of either kidney or pancreas acute rejection was also higher in the AA group (60% AA vs. 20% Caucasian, p = 0.06). TAC levels were comparable at specific times after transplantation, al-though there was a trend toward higher doses of TAC in the AA group to achieve therapeutic levels. The incidences of relaparotomy (30% AA vs. 20% Caucasian) and major infection (40% AA vs. 60% Caucasian) were similar between groups. Renal and pancreas allograft functions were comparable between groups at specific times after transplantation. CONCLUSIONS: These results suggest that SKPT in AA recipients may be associated with a higher incidence of rejection and immunologic graft loss compared to matched Caucasian controls.     

Maintenance immunosuppression with mycophenolate mofetil and corticosteroids in pediatric kidney transplantation: temporary benefit but not without risk

BACKGROUND: Aiming at reducing cyclosporine toxicity, we investigated safety and efficacy of mycophenolate mofetil (MMF) as an immunosuppressive drug in pediatric kidney transplantation compared with cyclosporine (CsA), both in combination with corticosteroids. METHODS: One year after kidney transplantation, children on triple immunosuppression, having experienced no more than one, steroid-sensitive, acute rejection episode, were randomized to withdrawal of either CsA or MMF and were followed for 2 yr. RESULTS: In each group, two patients had an acute rejection episode during withdrawal. Treatment failure occurred in 3 of 21 MMF and 5 of 23 CsA patients. Final analysis was for 18 patients in either group. A larger than 10 mL/min 1.73 m decrease in glomerular filtration rate was observed in more patients on CsA than on MMF (73% vs. 29%, P=0.019). No differences in blood pressure or nightly decrease of blood pressure were noted. Hypercholesterolism improved in the MMF (-16%), but not the CsA group (+5%, P<0.05), over the first, but not over both study years. Differences in triglycerid levels between groups were not shown. At study end, MMF patients tended to have lower hemoglobin levels than patients on CsA. Two MMF patients experienced a first acute rejection episode during the second study year, resulting in chronic transplant glomerulopathy with graft loss in one and deterioration of kidney function in the other. CONCLUSION: In pediatric kidney transplantation, maintenance immunosuppression with MMF together with corticosteroids has short-term benefits for kidney function and lipid pattern compared with CsA but is not without risk of complications.     

Improved outcomes after ABO-incompatible living-donor kidney transplantation after 4 weeks of treatment with mycophenolate mofetil

Hyperacute humoral rejection of ABO-incompatible kidney transplants limits the application of this procedure. We evaluated the effect of 4-week treatment with mycophenolate mofetil (MMF), a compound that inhibits antibody production by B cells, before ABO-incompatible living-donor kidney transplantation with tacrolimus as the primary immunosuppressant. In contrast with cases without MMF pretreatment, we did not observe any graft loss caused by hyperacute humoral rejection in the 18 patients who received MMF. Overall, the incidence of adverse events was comparable in the MMF-treated and -untreated groups. The administration of MMF 4 weeks before kidney transplant effectively inhibits B-cell function, suggesting a potential role for MMF in the prevention of humoral rejection.     

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.