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.     

Interaction of mycophenolate mofetil and HLA matching on renal allograft survival

INTRODUCTION: The importance of HLA matching for renal transplantation outcomes has been appreciated for several decades. It has been hypothesized that as pharmacologic immunosuppression becomes stronger and more specific, the impact of HLA matching may be vanishing. Mycophenolate Mofetil (MMF) has been demonstrated to both decrease acute rejection and improve three-year graft survival. It is possible that with new immunosuppressive regimens containing MMF the relative effect of HLA matching may be altered. To determine the relative impact of HLA matching in patients on MMF we undertook an analysis of the United States Renal Transplant Data Registry (USRDS). METHODS: All primary, solitary renal transplants registered at the USRDS between January 1995 and June 1997, on initial immunosuppression that included either MMF or AZA were followed until June 1998. Primary study end points were graft and patient survival. Kaplan-Meier analysis was performed to compare AZA vs. MMF treated patients by HLA mismatch. Cox proportional hazard models were used to investigate the interaction between HLA mismatch and AZA versus MMF therapy on the study endpoints. All multivariate analyses were corrected for 13 potential confounding pretransplant variables including intention to treat immunosuppression. RESULTS: A total of 19,675 patients were analyzed (8,459 on MMF and 11,216 on AZA). Overall three year graft survival was higher in the MMF group when compared to the AZA group (87% vs. 84% respectively P<0.001). For both AZA and MMF three-year graft survival improved with fewer HLA donor-recipient mismatches. Comparing zero antigen mismatches to six antigen mismatches, the relative improvement was comparable for both patients on AZA (92.4% vs. 80.6%) and MMF (95.2% vs. 82.9%). By Cox proportional hazard model the relative risk for graft loss decreased significantly in both the AZA and MMF treated patients with increased HLA matching. CONCLUSION: The use of MMF does not obviate the benefits of HLA matching, while HLA matching does not minimize the benefits of MMF on long term graft survival. Our study would suggest that HLA matching and MMF therapy are additive factors in decreasing the risk for renal allograft loss.     

Mycophenolate mofetil versus azathioprine in patients surviving the initial cardiac transplant hospitalization: an analysis of the Joint UNOS/ISHLT Thoracic Registry.

BACKGROUND: Although the randomized mycophenolate mofetil- (MMF) azathioprine (AZA) trial is likely applicable to cardiac transplantation in general, it was limited to select and usually larger cardiac transplant centers and suffered from substantial cross-over and failure of many patients to receive assigned treatment drug. METHODS: The Joint ISHLT/UNOS Thoracic Registry was analyzed for the effects of MMF versus AZA in patients 1) on a cyclosporine- (CsA) based immunosuppression protocol; 2) having survived long enough to be discharged from the transplant hospitalization. RESULTS: A total of 5599 patients (4942 CsA/AZA and 657 CsA/MMF) were included with no significant differences between the MMF and AZA groups in baseline characteristics with the exception of recipient age (50 vs. 47 years), donor age (29 vs. 28 years), ischemic time (3.0 vs. 2.9 hr), and pretransplant medical condition (more AZA patients in ICU, more MMF patients on VAD). Actuarial survival was greater in the MMF group compared to the AZA group in patients surviving the initial transplant hospitalization (1 year 96 vs. 93%, 3 years 91 vs. 86%, P=0.0012). This difference was confirmed in the logistic regression analysis of 3-year mortality showing a relative risk of 0.62 (P=0.011). CONCLUSIONS: These data provide independent support for the broad applicability of the positive results from the randomized MMF-AZA clinical trial in a substantially larger patient population and confirm improved survival in patients using mycophenolate mofetil compared to azathioprine late after cardiac transplantation.     

Low-dose versus high-dose cyclosporine induction protocols in renal transplantation

BACKGROUND: Current immunosuppressive therapies are effective to prevent acute rejection episodes (ARE) and graft loss following renal transplantation. Newer agents now make it possible to develop equally efficacious but better tolerated, less toxic strategies. We compared the efficacy of early low- versus high-dose cyclosporine (CsA) induction therapy in living donor renal transplantation. METHODS: In this single-center study, 90 consecutive recipients of living donor kidney transplants between November 2002 to October 2003 including 51 females and mean average age of 48.23 years were treated with either CsA (5 mg/kg/d) plus mycophenolae mofetil (MMF; 30 mg/kg/d) and prednisolone (1 mg/kg/d; group 1; n=42); or CsA (8 mg/kg/d) plus MMF (30 mg/kg/d) and prednisolone (1 mg/kg/d; group 2; n=48). The 2 groups were matched with respect to age, sex, underlying renal diseases, pretransplantation dialysis period, number of transplantations, and panel-reactive antibody tests. CsA dose tapering was initiated in the 2 group 3 months after transplantation. At the end of the first year, the CsA dose was 3.5 +/- 0.65 mg/kg in group 1 and 3.4 +/- 0.34 mg/kg in group 2. Prednisolone was tapered within the first 2 months, reaching 10 mg/d in all patients. The MMF dose remained unchanged. The 2 groups were compared with respect to ARE, patient and graft survivals, and clinical outcomes within 2 years after transplantation. RESULTS: There were no significant differences between the 2 groups with respect to clinical outcomes, including 2-year patient survival (97.62% vs 97.92%; P=.76), 2-year graft survival (80.32% vs 80.41%; P=.82), ARE (47.61% vs 52.08%; P=.09), or length of immediate postsurgical hospital stay, number of readmissions, total hospitalization days, posttransplantation diabetes mellitus, and infectious, cardiovascular, gastrointestinal, and hematologic complications. There was more hypertension (67.5% vs 50.23%; P=.007), hypertriglyceridemia (45.5% vs 32.64%; P=.005), and elevated liver enzymes in group 2 (12.5% vs 7.14%; P=.018). CONCLUSIONS: Compared with 8 mg/kg CsA induction therapy, the lower doses of CsA were effective, well tolerated, and safe with relatively fewer side effects.     

New immunosuppressive treatment in kidney transplantation

BACKGROUND: Mycophenolate mofetil (MMF) has been successfully introduced into clinical practice with evident benefits for renal transplant recipients. SUBJECTS AND METHODS: To evaluate some clinical results of MMF introduction, two groups of subjects underwent cadaveric renal transplants over the last 3 years and were retrospectively investigated. The first group (AZA group) contained 40 subjects (26 males and 14 females) on triple-drug therapy with steroids, cyclosporine and azathioprine (AZA). The second group (MMF group) contained 25 patients ( 19 males and 6 females) on the same regime with steroids and cyclosporine but MMF was administered as a third drug instead of AZA. The AZA group received renal transplant after a mean dialytic time of 32 +/- 19 months and the AZA group's dialytic time was 39.9 +/- 17 months. Clinical data, collected after a minimum 12 months observational period included a crude mortality rate and survival analysis recognized by Kaplan-Meyer curve, creatinine, creatinine clearance, rejection episodes and major clinical events such as infections and acute tubular necrosis. RESULTS: One subject died in each group. For kidney graft survival, Kaplan Meyer survival analysis showed a mean survival time of 1170.04 days in the AZA group vs 845 in the MMF group without statistical significance. Graft survival demonstrated 5:40 (12.5%) graft losses in the AZA group vs no kidney transplant loss in the MMF group (the only deceased patient had a well functioning kidney). The curve of graft cumulative proportion survival analysis demonstrated a more improved survival in the MMF group, but this difference did not reach a statistical significance (p = 0.07). Acute rejection episodes in the AZA group were 37.5% vs. 20% in the MMF group. In both groups, CMV infection was successfully treated with specific antiviral agents. CONCLUSIONS: MMF represents an important step towards induction and maintenance of immunosuppression. Our experience in a relatively small cohort investigated in a single center, demonstrates encouraging results regarding graft survival in comparison to those detected in conventional triple drug therapy. Surprisingly, in spite of stronger immunosuppressive treatment, the prevalence of CMV infections was not statistically different in the MMF versus the AZA group.     

Azathioprine in Liver Transplantation: A Reevaluation of Its Use and a Comparison with Mycophenolate Mofetil

Calcineurin inhibitors (CNIs) combined with steroids with or without azathioprine (AZA), have been a standard immunosuppression regimen after liver transplantation (LT). Since 2000 many centers have substituted AZA by mycophenolate mofetil (MMF). However, in LT the superiority of MMF over AZA is not clearly demonstrated. Therefore, we questioned the benefit of MMF versus AZA in LT with regard to rejection, renal dysfunction and hepatitis C virus (HCV) recurrence and survival. Using a literature search, relevant randomized controlled trials (RCT) and cohort studies were identified: two RCTs compared MMF to AZA only for acute rejection. Treated rejection was less with MMF in only one RCT (38.5% vs. 47.7%; p = 0.025), with no difference in patient and graft survival. No RCTs compared MMF and AZA in patients with CNI-related chronic renal dysfunction. Among two studies evaluating MMF, with substitution of AZA, one was stopped due to severe rejection. Recurrent HCV was less severe in 5/9 studies with AZA compared with 2/17 using MMF, six of which documented worse recurrence. Published data in LT show little, if any, clinical benefit of MMF versus AZA. RCTs should reevaluate AZA in LT. Evaluation of HCV replication and recurrence will be particularly important as AZA may have advantages over MMF.     

Causes of rehospitalization after renal transplantation; does age of recipient matter?

BACKGROUND: This study assessed the causes and related factors of rehospitalization following renal transplantation among elderly compared with younger patients. METHODS: We reviewed the charts of 567 patients rehospitalized after kidney transplantation from 2000 to 2006. According to age at the time of transplantation, hospitalizations were divided into two groups: group 1 (age >or=50 years) and group II (age 20 to 50 years). Demographics, clinical findings, causes for rehospitalization, patient outcomes (recovery, graft loss, death), intensive care unit (ICU) admission, length of hospital stay, time interval from transplantation to rehospitalization, as well as hospital costs were compared between the two groups. RESULTS: One hundred eighty-five (32.6%) rehospitalizations were charted for group I, who showed a higher proportion of admissions due to infection (42.2% vs 29.8%, P=.004) and macrovascular disease (3.8% vs 1.0%, P=.027) compared with group II. ICU admission (8.8% vs 2.4%, P=.001), mortality (10.2% vs 3.6%, P=.008), and hospital charges (1610 +/- 933 vs 931 +/- 850 purchase power parity dollars, P=.001) were also seen more frequently in group I but displayed a lower frequency of admissions due to graft rejection (20% vs 34.3%, P=.001). CONCLUSION: Recipient age at the time of transplantation was a main factor affecting rehospitalization among our patients.     

Reduced kidney transplant rejection rate and pharmacoeconomic advantage of mycophenolate mofetil.

BACKGROUND: Several multinational controlled clinical trials have shown that triple therapy immunosuppressive regimens which include mycophenolate mofetil (MMF), cyclosporin A (CSA) and steroids (S) are superior compared with conventional regimens which include azathioprine (AZA), CSA and S, mainly because MMF reduces the rate of acute rejection episodes in the first 6 months after kidney transplantation. Post-marketing studies are useful to evaluate the general applicability and costs of MMF-based immunosuppressive regimens. METHODS: Based on the excellent results of the published controlled clinical trials, we have changed the standard triple therapy immunosuppressive protocol (AZA+CSA+S) to an MMF-based regimen (MMF+CSA+S) at our centre. To analyse the impact of this change in regimen, we have monitored 6-month patient and graft survival, rejection rate, serum creatinine and CSA levels, as well as the costs of the immunosuppressive and anti-rejection treatments, in 40 consecutive renal transplant recipients (MMF group) and have compared the data with 40 consecutive patients transplanted immediately prior to the change in regimen (AZA group). RESULTS: Recipient and donor characteristics were similar in the AZA and MMF groups. Patient survival (37/40; 92.5% in the AZA group vs 38/40; 95% in the MMF group), graft survival (36/40 vs 36/40; both 90%) and serum creatinine (137+/-56 vs 139+/-44 micromol/l) after 6 months were not significantly different. However, the rate of acute rejection episodes (defined as a rise in creatinine without other obvious cause and treated at least with pulse steroids) was significantly reduced with MMF from 60 to 20% (P=0.0005). The resulting cost for rejection treatment was lowered 8-fold (from sFr. 2113 to 259 averaged per patient) and the number of transplant biopsies was lowered > 3-fold in the MMF group. The cost for the immunosuppressive therapy was increased 1.5-fold with MMF (from sFr. 5906 to 9231 per patient for the first 6 months). CONCLUSIONS: The change from AZA to MMF resulted in a significant reduction in early rejection episodes, resulting in fewer diagnostic procedures and rehospitalizations. The optimal long-term regimen in terms of patient and pharmacoeconomic benefits remains to be defined.     

Mycophenolate mofetil in pediatric renal transplantation

INTRODUCTION: Since kidney transplantation is the therapy of choice for children with end-stage renal disease (ESRD), we investigated the effects of mycophenolate mofetil (MMF) in pediatric renal transplantation. METHODS AND SUBJECTS: Two hundred sixteen children received renal transplants between 1985 and 2003: 100 patients received MMF with cyclosporine and prednisolone (cases), and 116 patients, azathioprine with cyclosporine and prednisolone (controls). RESULTS: The MMF group (100 patients) showed better graft survival and function than the AZA group (116 patients). Patients who received MMF immediately after transplantation experienced less graft loss and acute rejection episodes in the first 3 months after transplantation (P < .05). Patients who received MMF at the time of diagnosis of chronic rejection had stable renal function and remarkably better graft survival than those with chronic rejection who received AZA instead of MMF (P < .05). CONCLUSION: This study suggests that MMF may stop persistent graft dysfunction in chronic rejection, improving graft survival in the short and long terms posttransplantation.     

Efficacy of mycophenolate mofetil versus azathioprine after renal transplantation: a systematic review

INTRODUCTION: Our objective was to evaluate the efficacy of mycophenolate acid (MMF) versus azathioprine (AZA) after renal transplantation. MATERIALS AND METHODS: The following electronic databases were searched: Medline, Embase, Cochrane library, and Chinese Biomedicine database (CBM). Randomized controlled trials (RCTs) were subjected to Revman 4.11 for statistical analyses. RESULTS: Twenty-three RCTs were identified to compare MMF and AZA for antirejection, prophylaxis after renal transplantation. The data showed that MMF (2 g/d) was more beneficial than AZA to improve graft and long-term patient survivals, but there was no statistical differences between MMF (3 g/d) and AZA. Whether at 6 months or at 1 year after renal transplantation, the use of MMF (2 g/d) or MMF (3 g/d) markedly reduced the incidence of biopsy-proven rejection. CONCLUSION: Compared with AZA, MMF is a more potent immunosuppressive drug, that is more efficient in reducing the incidence of acute rejection episodes after renal transplantation. MMF can improve the graft and patient survival rate. The 2 g per day dosage is more acceptable.     

Mycophenolate mofetil may allow cyclosporine and steroid sparing in de novo heart transplant patients

BACKGROUND: Mycophenolate mofetil (MMF) provides superior prophylaxis against acute rejection when compared with azathioprine (AZA) in heart and renal transplantation. However, it remains unclear whether this results in improved survival or reduced morbidity after heart transplantation. METHOD: In a sequential study, 240 cardiac transplant patients were treated with either MMF (n=119) or AZA (n=121) both in combination with cyclosporine and corticosteroids after rabbit antithymocyte globulin induction. RESULTS: By protocol lower cyclosporine levels were targeted in the MMF group during the first year (e.g. 203+/-52 ng/mL MMF vs. 236+/-59 ng/mL AZA, P=0.0006 at 6 months). Patient survival at 1 year (82% MMF vs. 79% AZA, P=0.55) and at 3 years was similar in both groups. The cumulative probability of receiving antirejection treatment within 1 year was lower in the MMF group, as was biopsy-proven acute rejection with International Society of Heart and Lung Transplantation grade > or =3A (24% vs. 35%, P=0.03). The MMF group also had fewer episodes requiring cytolytic therapy (6% vs. 13%, P=0.04) and more patients had steroids withdrawn by 1 year (66% vs. 32%, P<0.001). Renal function was better in the MMF group with lower creatinine levels at 1 year (133+/-45 vs. 155+/-46 micromol/L, P=0.0004). Calculated creatinine clearance (Cockcroft and Gault formula) at 1 year was also better (MMF 74+/-32 mL/min vs. AZA 62+/-24 mL/min, P=0.004). CONCLUSION: Our results suggest that immunosuppression with MMF rather than AZA may allow lower cyclosporine levels, better renal function, and increased steroid weaning at 1 year while also achieving better control of acute rejection.     

Randomized trial of conversion from mycophenolate mofetil to azathioprine 6 months after renal allograft transplantation.

BACKGROUND: In the first year after renal allograft transplantation, triple therapy immunosuppression with cyclosporin (CsA), prednisone (P), and mycophenolate mofetil (MMF) is superior to a triple therapy treatment that includes azathioprine (AZA) instead of MMF. Whether long-term treatment with CsA-P-MMF is better than treatment with CsA-P-AZA is a matter of debate, as 3-year graft survival is similar in MMF- and AZA-treated patients. The purpose of the present study was to examine the short-term effect of changing MMF to AZA in low-risk renal allograft recipients 6 months after transplantation. METHOD: This was a randomized, open-label single-centre study, recruiting 48 low risk renal allograft recipients on CsA-P-MMF therapy 6 months after transplantation, comparing the outcome with continued MMF treatment (2 g b.i.d.) (group A, n=22) or switching MMF to AZA (1 mg/kg) treatment (group B, n=26). RESULTS: The outcome after a 6-months follow-up of patients in group A and group B was similar. Treatment failure rates (defined as clinically diagnosed acute rejection episodes) were 4.5% in group A and 3.8% in group B. There were no patient deaths and no graft failures during the 6-months observation period. Graft function was excellent and similar in both groups. CONCLUSION: Replacing MMF with AZA 6 months after transplantation in low-risk renal allograft recipients is safe and is not associated with altered graft function in the short term.     

A comparison of discharge immunosuppressive drug regimens in primary cadaveric kidney transplantation

BACKGROUND: Finding the best combination of immunosuppression is an important challenge in kidney transplantation. Current short-term (1- and 3-year) allograft survival is quite good, making it difficult to determine differences in therapeutic regimens without large sample sizes. Using data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network database, the current study provides substantial statistical power to analyze the outcomes for different immunosuppressive regimens. METHODS: To compare the effects of four discharge regimens (cyclosporine and azathioprine [CYA+AZA], CYA and mycophenolate mofetil [MMF], tacrolimus [TAC]+AZA, and TAC+MMF) on long-term survival, a multivariate Cox regression analysis was conducted on 19246 primary cadaveric kidney transplants during 1995 to 1998. RESULTS: Compared with CYA+AZA, the combination of CYA+MMF was associated with a 10% reduced risk of graft loss (relative risk [RR] 0.90, 95% confidence limit [CL] 0.84-0.96, P<0.001), whereas TAC+AZA was associated with an 18% reduced risk (RR 0.82, 95% CL 0.67-1.005, P=0.06) and TAC+MMF with a 20% reduced risk of graft loss (RR 0.80, 95% CL 0.71-0.89, P<0.001). All three regimens benefited patients regardless of delayed graft function (DGF) or early acute rejection status. In addition, in the absence of DGF, the combinations of CYA+MMF, TAC+AZA, and TAC+MMF were associated with a reduced risk of mortality compared with CYA+AZA. CONCLUSIONS: The major finding of this study was improved graft and patient survival associated with TAC+MMF and CYA+MMF in patients with or without DGF or early acute rejection.     

A prospective, randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 1 year

BACKGROUND: This is the 1-year report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation. METHODS: Prior to transplantation, recipients were randomized to receive tacrolimus plus corticosteroids with either sirolimus (n=185) or MMF (n=176). The incidence of biopsy-confirmed acute rejection at 6 months was the primary endpoint of the study. Patient and graft survival, renal function, study drug dosing and discontinuations were evaluated at 1 year. RESULTS: At 1 year, there was no difference in patient survival (95.7% sirolimus vs. 97.2% MMF; P=0.45) or graft survival (90.8% sirolimus vs. 94.3% MMF; P=0.22). Patients without delayed graft function (DGF) receiving MMF had significantly better graft survival (99% vs. 93%; P=0.01). Patients receiving a transplant from a live donor had a trend towards better graft survival with MMF as compared to sirolimus (98% vs. 91%; P=0.07). Patients receiving sirolimus had a significantly higher incidence of study drug discontinuation (26.5% vs. 14.8% MMF; P=0.006). Patients receiving MMF had significantly better renal function as shown by median serum creatinine levels (1.3 mg/dL vs. 1.5 mg/dL; P=0.03) and a trend towards higher calculated creatinine clearance (CrCl), (58.4 ml/min vs. 54.3 ml/min; P=0.06). More patients in the sirolimus group had a serum creatinine >2.0 mg/dL, (20.4% vs. 11.0%; P=0.02). CONCLUSIONS: Tacrolimus is safe and effective in live and deceased donor kidney transplantation when given in combination with sirolimus or MMF. Patient and graft survival were excellent in both arms. Renal function is superior for patients treated with tacrolimus + MMF combination.     

Randomized, prospective trial of mycophenolate mofetil versus azathioprine for prevention of acute renal allograft rejection after simultaneous kidney-pancreas transplantation

BACKGROUND: In simultaneous kidney-pancreas (SPK) transplantation, manifestations of renal allograft rejection typically become evident before those of pancreatic rejection. This study compared mycophenolate mofetil (MMF) and azathioprine (AZA) in prevention of renal rejection after primary SPK transplantation. METHODS: In an open-label, randomized, multicenter study, patients received MMF 1.5 g twice daily (n=74) or AZA 1-3 mg/kg daily (n=76) for 1 year after transplantation. The incidence of rejection was assessed at 6 months. Adverse events were tracked through 1 year. Survival data are reported through 2 years. RESULTS: At 6 months, efficacy results for MMF vs. AZA patients, respectively, were the following: rejection (27% vs. 39%); rejection or death (34% vs. 42%); rejection, graft loss, death, or premature withdrawal (i.e., treatment failure; 41% vs. 55%). Six-month efficacy trends favored MMF, and time to rejection or treatment failure was significantly longer when compared with AZA (P=0.049). One-year efficacy results for MMF vs. AZA patients, respectively, were the following: treatment of renal rejection (35% vs. 47%); renal allograft loss or death (9% vs. 12%); pancreas allograft loss or death (15% vs. 14%). Five MMF patients (7%) and four (5%) in the AZA group died. More MMF than AZA patients developed opportunistic infections (54% vs. 38%), but the pathogens did not differ. CONCLUSIONS: Trends for most efficacy parameters favored MMF over AZA, and time to renal allograft rejection or treatment failure was statistically significantly longer for MMF. The use of MMF in the treatment of SPK recipients is a useful advance.     

Anemia in the period immediately following renal transplantation

INTRODUCTION: Anemia remains frequent in the first month following renal transplantation and is a risk factor for cardiovascular accidents. The purpose of this study was to analyze the prevalence of anemia during this period notably among different immunosuppressive treatment groups. METHODS: In this study, we entered the patients who had received a renal allograft in our transplant unit from 1993 to 2003, including patients who had received azathioprine (AZA) from 1993 to 1996 and mycophenolate mofetil (MMF) from 1996 to 2003. No patient received rHu-erythropoietin after transplantation during that period. A mathematical model normalized the hemoglobin (Hb) threshold level at which blood transfusion was decided and Hb on admission. RESULTS: One hundred and eighty-eight patients on AZA and 223 on MMF were included in the analysis. The mean age +/- SD was 41 +/- 12 years in the AZA group, and 45 +/- 12 years in the MMF group (P < .006). Before the transplantation, Hb was higher in the MMF group (11.4 +/- 1.9 vs 10.2 +/- 2 g/dL, P < .0001). After normalization at a threshold level of transfusion of 7 g/dL, transfusions were more frequent among the MMF group (72% vs 48%, P < .0001). Double therapy with MMF (1500 mg/d) + steroids or therapy with MMF (750 mg/d) + tacrolimus + steroids increased the risk of transfusion compared to the AZA group. MMF (750 mg/d) + cyclosporine conferred a similar risk of transfusion compared with the AZA group. CONCLUSION: MMF alone or in association with tacrolimus is associated with an increased risk of anemia and transfusion in the immediate posttransplantation period.     

Effect of mycophenolate mofetil on long-term outcomes in African american renal transplant recipients

African American renal transplant recipients have poorer graft survival. A study using the United States Renal Data Registry documented an improvement in graft survival for patients who took mycophenolate mofetil (MMF) compared with azathioprine (AZA). This analysis did not address the impact of MMF on African American renal transplant recipients. The present study aimed to quantify potential beneficial effects of MMF therapy on long-term renal allograft survival in African Americans. With the use of the United States Renal Data Registry, all adult Caucasian and African American patients who had received a primary renal transplant between 1988 and 1997 were analyzed by Kaplan-Meier analysis and Cox proportional hazard models. Primary study end points were death with a functioning graft and graft failure censored for death. A total of 57,926 patients were studied. For African Americans, 3-yr patient survival was 96.3 versus 93.2% (P<0.001) for MMF and AZA, respectively. Three-yr death-censored graft survival for African Americans was 85.8 versus 75.1% (P<0.001) for MMF and AZA, respectively. For Caucasians, 3-yr patient survival was 97.3 versus 93.2% for MMF and AZA, respectively. Three-yr death-censored graft survival for Caucasians was 90.1 versus 86.4% (P<0.001) for MMF and AZA, respectively. By multivariate analysis, MMF was associated with a significant reduction in the relative risk for all study end points in African Americans. MMF therapy is associated with both improved patient and death-censored graft survival in African American renal transplant recipients. This benefit is comparable to the benefit of MMF in Caucasian renal transplant recipients.     

Pediatric renal transplantation with mycophenolate mofetil-based immunosuppression without induction: results after three years

BACKGROUND: Mycophenolate mofetil (MMF)-based immunosuppression has reduced the acute rejection rate in adults and in children in the early posttransplantation period. Three-year posttransplantation results have been reported for adults but not for children thus far. In the present open-labeled study, patients 18 years old and younger were evaluated prospectively for up to 3 years after renal transplantation (RTX). METHODS: Eighty-six patients receiving MMF in combination with cyclosporine and prednisone without induction were evaluated for patient survival, transplant survival, renal function, arterial blood pressure, adverse events, and opportunistic infections. These patients were compared with a historic control group (n=54) receiving azathioprine (AZA) instead of MMF. RESULTS: Patient survival after 3 years was 98.8% in the MMF group and 94.4% in the AZA group (NS). Intent-to-treat analysis of graft survival demonstrated superiority for MMF (98% vs. 80%; P<0.001). Cumulative acute rejection episodes occurred in 47% of patients in the MMF group versus 61% in the AZA group (P<0.05). Renal function was not significantly different, neither after 3 years nor in the long-term calculation. Antihypertensive medication was administered to 73% to 84% of patients, similar in both groups. Opportunistic infections were recorded only for MMF. Infection rates were comparable to those reported in adults. CONCLUSIONS: These results suggest that MMF is safe and beneficial as a longer term maintenance immunosuppressive drug in children and adolescents.     

Bayesian approach to predict hospital mortality of intensive care readmissions during the same hospitalisation

No specific prognostic model has been developed for patients readmitted to the intensive care unit (ICU) during the same hospitalisation. This study assesses the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) II predicted mortality measured at the time of ICU readmission and whether incorporating information prior to the readmission will improve its performance to predict hospital mortality of patients readmitted to ICU during the same hospitalisation. A total of 602 readmissions during the same hospitalisation between 1987 and 2002 were identified. The first admission APACHE II predicted mortality was significantly associated with the hospital mortality only in the subgroup of patients readmitted within seven days of ICU discharge (odds ratio 1.16, 95% confidence interval 1.01 to 1.34; P = 0.035). In the subgroups of patients readmitted within seven days of discharge, the readmission APACHE II predicted mortality was also significantly better than the first admission APACHE II predicted mortality in discriminating between survivors and non-survivors (area under the receiver operating characteristic curve: 0.785 vs. 0.676, z statistic = 2.93; P = 0.003). Incorporating the first admission APACHE II predicted mortality to the readmission APACHE II predicted mortality, either by multilevel likelihood ratios or logistic regression, did not significantly improve its discrimination (area under the receiver operating characteristic curve: 0.792 vs. 0.785, z statistic = 0.52; P = 0.603). Our results suggested that information on prior ICU admission during the same hospitalisation is not as important as the severity of illness measured at the time of readmission in determining the mortality of intensive care readmissions during the same hospitalisation.     

Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation

BACKGROUND: Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation. METHODS: A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year. RESULTS: There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups. CONCLUSIONS: All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.