Impact of mycophenolate mofetil dose posttransplantation on 12-month renal function: analysis of the MOST database

INTRODUCTION: Mycophenolate mofetil (MMF) has greatly reduced the risk of acute rejection episodes (ARE) after renal transplantation, but dose reductions/withdrawals could jeopardize long-term results. METHODS: The MOST database of "de novo" patients treated with MMF at month 1 and functioning grafts at month 12 were divided into 2 groups: groups 1, 2 g MMF at month 1 and month 12; and group 2, 2 g MMF at month 1 but MMF <2 g at month 12 to evaluate renal function glonerular filtration rate (GFR). RESULTS: In this study, 1136 patients were receiving 2 g MMF at month 1. On month 12, 645 were on 2 g (56.8%, group 1) and 431 were on <2 g (43.2%, group 2). Group 1 included younger recipients of younger donors with fewer patients with delayed graft function (DGF). Group 1 showed more ARE during month 1 and more patients who received induction. Mean Neoral daily doses at month 1/month 12 were 5.3/3.0 and 5.3/3.1 mg/kg in group 1 and group 2, respectively (P = .05 at month 12). GFR in group 1 and group 2 were 59.06 (CI 57.10-60.60) and 53.81 (CI 52-55.7) at month 1 (P < .001); 63.7 (CI 62.1-65.30) and 55.9 (CI 54.1-57.7) mL/min*1.73 m(2) at month 12 (P < .001). The mean increases in GFR between month 1 and month 12 were 4.64 and 1.94 mL/min*1.73 m(2), respectively (P < .05). A multivariate analysis also included 795 patients from the "maintenance" patient database with retrospective detailed information. The following parameters were highly predictive for good renal function at month 12: donor age younger than 60 years, recipient age younger than 60 years, immediate graft function, 12-month MMF dose = 2 g, absence of CMV infection, and 12-month Neoral dose <3 mg/kg/d. CONCLUSIONS: Maintenance of MMF dose at 2 g/d during the first year appears to facilitate the attainment of optimal renal function at 12-months after kidney transplantation.     

Cyclosporine and mycophenolate mofetil 48 hours before renal transplantation enables the use of low cyclosporine doses and achieves better graft function

Reducing calcineurin-inhibitor induced nephrotoxicity and simultaneously avoiding long-term side effects are desirable goals in renal transplantation. We examined the hypothesis that administration of cyclosporine and mycophenolate mofetil (MMF) 48 hours before renal transplantation allows reduction in the target cyclosporine C2 concentration, thus decreasing toxicity and improving graft function. We enrolled 80 kidney recipients in a single-center study comparing 2 cyclosporine-based protocols. Group I patients (n = 40) received a standard dose of cyclosporine (blood cyclosporine C2, 800-1500 ng/mL) with MMF and standard doses of corticosteroids. Group II patients (n = 40) were treated with a low dose of cyclosporine (blood cyclosporine C2, 450-800 ng/mL) and MMF plus low doses of corticosteroids after induction 48 hours before surgery with cyclosporine and MMF. Patient (97.5% vs 100%) and graft survivals (92.5% vs 95%) at 1 year were not different between the groups, although patients in group II experienced significantly fewer acute rejection episodes (10% vs 30%; P < .01). Delayed graft function occurred less often among group I than group II (17.5 vs 20%), but the difference was not significant. Graft function at 1 year was significantly better among group II (serum creatinine 1.31 vs 1.64 mg/dL and creatinine clearance 63 mL/min versus 47 mL/min; P < .05). We concluded that administration of cyclosporine and MMF 48 hours before renal transplantation allowed the safe effective use of low target C2 cyclosporine concentrations, enabling an early decrease in cyclosporine dose. These preliminary results indicated better 1-year graft function compared with the normal cyclosporine dose regimen.     

Impact of Cyclosporine Reduction With MMF: A Randomized Trial in Chronic Allograft Dysfunction. The ''Reference'' Study

Long-term use of calcineurine inhibitors (CNIs) may contribute to the development of chronic allograft dysfunction (CAD). We investigate the impact of the introduction of MMF combined with cyclosporine (CsA) 50% dose reduction. An open, randomized, controlled, multicenter, prospective study was conducted in 103 patients, receiving a CsA-based therapy with a serum creatinine between 1.7-3.4 mg/dL, more than 1 year after transplantation. They were randomized to receive MMF with half dose of CsA (MMF group) or to continue their maintenance CsA dose (control group). A total of 96 weeks after randomization, the evolution of renal function assessed by regression line analysis of 1/SeCr improved in the MMF group (positive slope) vs. the control group (negative slope), 4.2 x 10(-4) vs. -3.0 x 10(-4), respectively (p < 0.001). Concurrently, the absolute renal function improved significantly in the MMF group. No episode of biopsy-proven acute rejection occurred. One patient in each group lost his graft because of biopsy-proven chronic allograft nephropathy. There was a significant decrease of triglycerides level in the MMF group. Anemia and diarrhea were statistically more frequent in the MMF group. In CAD, the reduction of CsA in the presence of MMF results in significant improvement in renal function during a 2-year follow-up.     

Tacrolimus in induction immunosuppressive treatment in renal transplantation: comparison with cyclosporine

The aim of the study was to compare the efficacy and safety of induction immunosuppression therapies based on tacrolimus or cyclosporine (CsA) in kidney transplantation. The 240 kidney allograft recipients were divided into two groups: group 1 (n=94) received tacrolimus (.01 mg/kg per day), mycophenolate mofetil (MMF, 2 g/d), and steroids (30 mg/d); and group 2 (n=146) CsA (6 mg/kg per day), MMF (2 g/d), and steroids (30 mg/d). Antilymphocyte serum was administered in cases of acute tubular necrosis. The acute rejection rate was higher among group 2 (30.6%) compared with group 1 patients (12.2%) (P=.001). There were no significant differences between the groups in terms of age, gender, body surface area, serologic virus markers (in donor and recipient), baseline creatinine levels, cause of death, HLA incompatibilities, response to acute tubular necrosis, and number of dialysis sessions. We conclude that both immunosuppressive regimens are effective and safe in kidney transplantation. The survival rates of patients and grafts were similar, but the incidence and degree of acute rejection events were reduced in group 1; this finding may forecast a decreased incidence of chronic renal allograft nephropathy.     

Mycophenolate mofetil tolerability and dose changes in tacrolimus-treated renal allograft recipients

Mycophenolate mofetil (MMF) reduces acute rejection episodes (AREs) and may be associated with better renal graft survival than azathioprine. However, MMF-related adverse events are frequent; dose reduction or even withdrawal are quite common. Between 1999 and 2003, 115 renal transplantation patients were treated with tacrolimus, MMF, and steroids. An observational study was undertaken until graft loss (n = 7), death with a functioning graft (n = 2), or October 31, 2005 (mean follow-up-50 months). We assessed MMF dose reductions due to adverse events with the possible consequences on AREs and graft function. Treated acute ARE occurred in 11.3% of recipients, all of which were steroid-responsive. The median MMF initial daily dose was 1000 mg. In 44 patients (38.3%), the MMF dose was not changed; in 48 (41.7%) it was reduced; and in 23 (20%), withdrawn. The causes for dose modification were diarrhea (n = 33, 28.7% of all patients), leukopenia (n = 22, 19.1%), both of these (n = 7, 6.1%), or other events (n = 9, 7.8%). No AREs were attributed to MMF dose changes. Tacrolimus blood levels were higher at 3 years and serum creatinine values at 4 years among patients with dose changes (8.43 +/- 2.42 vs 7.37 +/- 2.23 ng/mL; P = .051 and 1.75 +/- 0.71 vs 1.48 +/- 0.38 mg/dL; P = .038, respectively). The need for MMF dose reduction or withdrawal was frequent in our patients with diarrhea or leukopenia during treatment with tacrolimus, MMF, and steroids. These adverse event-related changes were not associated with AREs, but produced deleterious effects on long-term graft function.     

Randomized study on the conversion of treatment with cyclosporine to azathioprine or mycophenolate mofetil followed by dose reduction

BACKGROUND: The introduction of cyclosporine (CsA) in kidney transplantation has improved early graft survival. However, its long-term use is associated with impairment of renal function and increased cardiovascular risk factors. To avoid CsA-related long-term adverse effects, patients were converted to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation. METHODS: Between September 1995 and January 1997, 64 stable renal transplant recipients on CsA and prednisone treatment were included in a prospective, randomized study. Patients were randomized for conversion of CsA to 2 mg/kg AZA (n=30) or 1 g of MMF twice daily (n=34). All patients remained on low-dose steroids. To decrease the total immunosuppressive load, a dose reduction in MMF and AZA was performed at 4 and again at 8 months after conversion. Mycophenolic acid trough levels were measured at regular intervals. RESULTS: After conversion, a decrease in serum creatinine was found for both groups: for MMF, 132 to 109 micromol/L (P=0.016); and for AZA, 123 to 112 micromol/L (P<0.0001). After conversion, more acute rejections occurred in the AZA group (11/30) compared to the MMF group (4/34) (P=0.04). Dose reduction of MMF to 500 mg twice daily and of AZA to 1.0 mg/kg elicited three rejections in both groups. The incidence of side effects and infections were similar. CONCLUSION: Discontinuation of CsA spared renal function. In patients converted to MMF significantly less rejections occurred compared to patients converted to AZA. Furthermore, dose reduction of both AZA and MMF is possible in the majority (72%) of the patients.     

Tacrolimus or cyclosporine: which is the better partner for mycophenolate mofetil in heart transplant recipients?

BACKGROUND: The aim of this single-center study was to investigate whether trough level adjusted mycophenolate mofetil (MMF) is more efficacious in combination with tacrolimus (TAC) or cyclosporine (CsA) and to evaluate the impact of either drug on MMF dosage. METHODS: Sixty patients (TAC, n = 30; CsA, n = 30) undergoing heart transplantation were randomized into a prospective, open-label, controlled trial. Immunosuppression consisted of TAC or CsA in combination with MMF and corticosteroids. Target blood trough levels of TAC, CsA, and mycophenolic acid (MPA) were in the range of 10 to 15 ng/mL, 100 to 300 ng/mL, and 1.5 to 4.0 microg/mL, respectively. Acute rejection episodes (ARE); survival data; and adverse events with a special emphasis on infections, diabetes, hypertension, hypercholesterolemia, and the development of graft vessel disease (GVD) were recorded. RESULTS: Baseline characteristics were well balanced. All patients were successfully withdrawn from corticosteroids within 6 months of transplant. Freedom from acute rejection was significantly higher (P = 0.0001) and the incidence of ARE per 100 patient days significantly lower in the TAC-MMF group than in the CsA-MMF group (0.03 vs. 0.15; P = 0.00007). Overall patient survival during follow-up was similar (93% vs. 90%). To achieve the targeted MPA blood levels, a significantly lower dose of MMF was required for TAC versus CsA patients. After a follow-up time of 2 years, the mean GVD score was 1.85 +/- 3.18 in the TAC-MMF group and 3.95 +/- 4.8 in the CsA-MMF group (P = 0.08). CONCLUSIONS: At the selected doses and target levels for TAC and CsA used in this study, trough level adjusted MMF was more efficacious in combination with TAC for prevention of ARE. Furthermore, CsA patients need significantly more MMF to achieve similar MPA levels.     

Cyclosporine levels at 2 hours after dose and body mass index in relation to graft function in renal transplant patients treated with azathioprine or mycophenolate mofetil

The aim of this study was to evaluate the effect of C(2) levels on renal graft function in relation to body mass index (BMI). This retrospective study of 95 renal transplant patients included 53 on AZA and 42 on MMF at 3.1 years after transplantation. The cohort was divided into groups according to their C(2) levels, namely <600 ng/mL, 600 to 900 ng/mL, or >900 ng/mL, and according to BMI (>26 kg/m(2)). In every group, we evaluated the percentage of patients with an increase in creatinine by 1 mg/dL or >/=50% from the first year posttransplant. There was no difference in age, gender, graft source, and dose of corticosteroids or CsA between the groups. Patients on AZA with C(2) 600 to 900 ng/mL showed a lower prevalence of renal dysfunction (3.4%) than those with C(2) levels <600 ng/mL (14.3%) or >900 ng/mL (20%). Seventeen percent of the patients on AZA and 11.9% on MMF had BMI >26 kg/m(2) (P = NS). An increased serum creatinine was present in 22.2% of patients with BMI >26 kg/m(2) in the AZA group vs 20% in the cohort MMF (P = NS). These findings suggest that long-standing renal recipients on AZA with C(2) levels of between 600 and 900 ng/mL show better preservation of renal function. We did not identify differences on the basis of C(2) levels in MMF-treated recipients. The influence of BMI on long-term graft function seemed to be independent of AZA or MMF therapy.     

Conversion from cyclosporine A to mycophenolate mofetil protects recipient kidney and prevents intimal hyperplasia in rat aortic allografts

BACKGROUND: Recent studies have demonstrated that complete conversion from cyclosporine A (CsA) to mycophenolate mofetil (MMF) prolongs graft survival in patients undergoing clinical organ transplantation. We investigated the effects of conversion from CsA to MMF on recipient kidneys and transplant arteriosclerosis in a rat aortic allograft model as a high responder combination. METHODS: DA (MHC haplotype, RT1a) rat abdominal aortic grafts were orthotopically transplanted into Lewis (RT1l) rats. The recipients were divided into four oral treatment groups: (1) vehicle group, (2) CsA group (15 mg/kg/day), (3) CsA/MMF40 group (conversion from CsA 15 mg/kg/day to MMF 40 mg/kg/day on day 14), and (4) CsA/MMF20 group (conversion from CsA 15 mg/kg/day to MMF 20 mg/kg/day on day 14). On day 28 after transplantation, the rats were sacrificed and the hematoserological parameters were analyzed. The grafted aortas and recipient kidneys also were evaluated histologically and immunohistochemically. RESULTS: The CsA group developed serological renal dysfunction, arteriolar hyalinosis, and apoptosis in the recipient kidneys, whereas the CsA/MMF40 and CsA/MMF20 groups did not. In the vehicle group, we observed remarkable intimal hyperplasia and marked inflammatory cell infiltration including macrophages and T cells. In the CsA group, intimal hyperplasia was evident without infiltration of macrophages or T cells. In the CsA/MMF40 and CsA/MMF20 groups, intimal hyperplasia was abrogated, while adventitial infiltration of and adhesion to the endothelium by macrophages and T cells occurred. CONCLUSIONS: Conversion from CsA to MMF protected recipient kidneys and prevented transplant arteriosclerosis. However, insufficient immunosuppression by MMF might reactivate immune cells. This conversion therapy has preventive potential in transplant patients with CsA-associated nephrotoxicity and transplant arteriosclerosis.     

骁悉对肾移植术后感染的影响

目的观察骁悉(MMF)对肾移植术后感染的影响。方法将90例肾移植术后患者分为两组．1997年以前手术的56例为硫唑嘌呤(Aza)组,免疫抑制剂为环孢素A(CsA)加Aza加泼尼松;1998～1999年1月手术的34例为MMF组,免疫抑制剂为CsA加MMF加泼尼松。Aza组CsA起始用量为6mg/(kg·d-1),MMF组为5mg/(kg·d-1),以后根据血药浓度进行调整。结果90例肾移植患者术后总的感染率为17.8％,其中Aza组为21.4％(12/56),2例死亡;MMF组为11.8％(4/34),无死亡病例。两者之间感染率差异有显著性意义(P＜0.05)。结论用MMF代替Aza可以减少肾移植术后的感染率,并提高移植肾成活率。     

Usefulness and Safety of High-dose Mizoribine on ABO-incompatible Living Related Kidney Transplantation Using Anti-cd20 and Anti-cd25 Antibodies Without Splenectomy: 3-year Results

Background

Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but has a less potent immunosuppressive effect up to 3 mg/kg/d. We previously reported that high-dose MZR, at 6 mg/kg/d, would be effective and safe for ABO-incompatible(ABO-i) living donor kidney transplantation (LDKT) patients when combined with cyclosporine (CsA) or tacrolimus(FK), anti-CD20 and anti-CD25 monoclonal antibodies, and corticosteroid without splenectomy in a 1-year study. Therefore, we observed these patients for 3 years.

Methods

From 2007 to 2010, we encountered 24 cases of ABO-i LDKT using anti-CD20 and anti-CD25 monoclonal antibodies without splenectomy. The pretransplantation immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF, 25 mg/kg/d), prednisolone, calcineurin inhibitor (CNI; CsA 7 mg/kg or (FK 0.2 mg/kg) and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LDKT up to several times according to the antibody titer. The post-transplantation regimen consisted of high-dose MZR (6 mg/kg/d) instead of MMF (MZR group, N = 12) .

Results

The 3-year graft survival rates for the MZR and MMF groups were 91.7% and 100%, respectively. Serum creatinine levels for the MZR and MMF groups were 1.44 mg/dL and 1.31 mg/dL at 1 year, 1.55 mg/dL and 1.41 mg/dL at 2 years, and 1.51 mg/dL and 1.48 mg/dL at 3 years, respectively (not significant [NS]). The MZR group did not show a higher rate of elevated serum uric acid values. The percentage of patients who were administered anti-uric medication was 42.5% (5/12) in the MZR group and 50% (6/12) in the MMF group (P = NS) at the third year. Severe infection, such as cytomegalovirus, herpes zoster, was not observed at the second and third years in both groups.

Conclusion

A high-dose MZR regimen including CNI (CsA or FK), steroid, and anti-CD20 and anti-CD25 antibodies without splenectomy was effective and safe in ABO-i renal transplantation.     

Impact of long-term immunosuppression with cyclosporin A on serum lipids in stable renal transplant recipients

Abstract. To determine the impact of long-term immunosuppression on serum lipids in stable renal graft recipients we measured serum lipids and apolipoprotein B concentrations in 20 patients receiving therapy with cyclosporin (CsA) and low-dose prednisolone (CsA/P) and in 18 patients on therapy with azathioprine and maintenance steroids (Aza/P). The patients were matched for age, body mass index, primary renal disease and dose of prednisolone, but not for the duration in transplantation and serum creatinine concentration. Triglyceride concentrations were significantly higher in the CsA/P group than in Aza/P-treated patients: 2.62 ± 0.35 vs 1.62 ± 0.23 mmol/l ( P < 0.05). Similarly, total cholesterol (C) levels were significantly more elevated in the CsA/P recipients than in the other group: 7.4410.32 vs 5.84 ± 0.25 (F<0.02). CsA/P patients had higher serum levels of LDL-C (4.79 ± 0.20 vs 3.43 ± 0.19 mmol/l ( P < 0.001) and apolipoprotein B concentrations (191 ± 13 vs 128 ± 9 mg/dl; P < 0.001). CsA/P and Aza/P recipients had similar concentrations of HDL-C (1.73 ± 0.13 vs 1.52 ± 0.09 mmol/l; NS). We conclude that in stable renal graft recipients with good transplant function long-term immunosuppression with CsA/P is associated with a more atherogenic lipid status than therapy with Aza/P.     

Avoidance of cyclosporine in renal transplantation: effects of daclizumab, mycophenolate mofetil, and steroids

Cyclosporine (CsA) has been implicated in both acute and chronic graft dysfunction. The addition of humanized IL-2 receptor antibody daclizumab (DZB) to CsA-based immunosuppression decreases the rate of acute renal transplant rejection. Therefore, 45 patients were evaluated in an immunosuppressive protocol that included DZB, mycophenolate mofetil (MMF), and steroids without CsA. This was a prospective, nonrandomized, open-label trial of the efficacy and safety of the treatment. DZB was given intravenously at 2 mg/kg before transplantation and then at 1 mg/kg every 2 wk for four doses, MMF was given orally at 3 g/d, and methylprednisolone/prednisone was given at 7 mg/kg per day and tapered to 15 mg/d at 6 mo. CsA was added to the regimen when patients developed acute rejection episodes or adverse effects to steroids or MMF; 49% of patients were spared CsA maintenance. Patients without CsA had lower serum creatinine at 6 mo and needed fewer medications to control BP. Incidence of biopsyproven rejections was 31% and occurred early (median, 10 d). These rejection episodes occurred earlier in cadaver transplants (median, 7 d) and later in living donor transplants (median, 62 days). Acute rejections occurred at a higher frequency (46% versus 34%) and earlier (6.5 versus 15 d) in patients with delayed graft function compared with patients without delayed graft function. Most of the rejections were moderate and easily reversible. The actuarial 1-yr graft survival was 95% with 100% patient survival.     

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.     

Influence of cytomegalovirus disease on early and late renal graft function

The role of cytomegalovirus (CMV) disease to induce chronic nephropathy using new immunosuppressive regimens is debated. This study sought to assess the influence of CMV disease on early and late graft function in relation to immunosuppressive therapy. Among 456 renal recipients transplanted from 1997 to 2003, 95 were diagnosed with CMV disease on the basis of clinical symptoms and the presence of pp65 protein. The patients were divided into 2 groups according to their immunosuppressive regimen: group I included 43 patients treated with cyclosporine (CsA), azathioprine (AZA), and prednisone (P); group II, 52 patients treated with calcineurin inhibitor (CI), mycophenolate mofetil (MMF), and P. A control group of 90 CMV disease-free renal recipients were transplanted in 2001. CMV disease occurred in 20.8% of renal recipients: 14.8% from group I and 25.5% from group II. CMV disease was diagnosed in 73 patients (76.8%) before the third month after transplantation. An acute rejection episode (ARE) appeared in 42 patients, of whom 31 had CMV disease diagnosed within 1 month after ARE, while 5 before an ARE. In six patients ARE was not time related to CMV disease. The serum creatinine values at 6 months after transplantation were significantly higher among the CMV versus control groups: 1.69 and 1.76 vs 1.49 (P < .05). In patients with ARE and CMV disease, the serum creatinine value was also higher at 6 and 12 months after transplantation compared with patients without an ARE (P < .03). One- and 3-year graft survival rates were 95.1% and 83.7% in group I versus 93.4% and 86.5% in group II versus 95.4% and 90.2% in the control group. In conclusion, CMV disease showed a negative impact on early graft function independent of the immunosuppressive regimen, an effect that was emphasized by an ARE.     

肾移植患者术后早期应用霉酚酸酯的临床观察

目的 观察肾移植术后早期不同剂量霉酚酸酯（ＭＭＦ）与环孢素Ａ（ＣｓＡ）和泼尼松（Ｐｒｅｄ）联用预防急性排斥反应的效果及安全性。方法 将６４例肾移植患者分为３组,分别给予ＭＭＦ２．０ｇ／ｄ（Ａ组）、１．５ｇ／ｄ（Ｂ组）及Ａｚａ ５０～１００ｍｇ／ｄ（Ｃ组）,每组均联用ＣｓＡ及Ｐｒｅｄ（剂量相同）。观察肾移植术后６个月内急性排斥反应的发生率、移植肾功能及药物的副作用。结果 Ａ、Ｂ、Ｃ组急性排斥反应的发     

Withdrawal of cyclosporine or prednisone six months after kidney transplantation in patients on triple drug therapy: a randomized, prospective, multicenter study

Uncertainty exists regarding the necessity of continuing triple therapy consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx, 212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute rejection occurred in 14 (22%) of 63 patients after CsA withdrawal compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1 (1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic rejection was present in one patient in the control group, in nine patients after CsA withdrawal (P = 0.006 versus control group); and in four patients after discontinuation of Pred (NS). Graft loss occurred in two versus one patient after CsA or Pred withdrawal, respectively, and in two patients in the control group (NS). Patients who successfully withdrew CsA had a significantly lower serum creatinine during follow-up. Pred withdrawal resulted in a reduction in mean arterial pressure, and the total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal at 6 mo after RTx results in a significantly increased incidence of biopsy-proven acute and chronic rejection. Pred withdrawal was safe and resulted in a reduction in mean arterial pressure. However, patient and graft survival and renal function 2 yr after RTx were not different among groups.     

霉酚酸酯防治肾移植后排斥反应的效果及安全性

目的 探讨霉酚酸酯（ＭＭＦ）防治肾移植术后急性排挤反应（ＡＲ）的效果和安全性。方法 １２４例肾移植受者随机分为ＭＭＦ组（４８例）及硫唑嘌呤组（Ａｚａ组,７６例）,观察２个患者术后３个月内ＡＲ、难治性急性排斥（ＣＲＲ）的发生率及并发症。结果ＭＭＦ组及Ａｚａ组在患者死亡率、移植肾失功率等方面的差异无显著性;ＭＭＦ组的ＡＲ发生率、ＣＲＲ发生率明显低于Ａｚａ组;以ＭＭＦ３．０ｇ／ｄ治疗ＣＲＲ,其效果与单     

Cardiovascular risk profile in nondiabetic renal transplant patients: cyclosporine versus tacrolimus

Calcineurin inhibitors (CIs) contribute to cardiovascular risk (CR) in renal transplant (RT) patients. However, the CR profile in RT patients without preexistent diabetes is not well known. We compared CR factors in 191 nondiabetic RT recipients with functioning grafts beyond 1 year, receivingly either CsA (Neoral; n=100) or tacrolimus (Tac; n= 91). Clinical data and pretransplant CR profiles were similar in both groups. There were no differences in acute rejection episodes and graft survival rates during follow-up. The overall proportions of posttransplant diabetes (9% versus 6%), and of hypertension (73% vs 63%) were similar in both groups. Hyperlipidemia was more frequent in the CsA group (58% vs 31%; P=.0001). The cholesterol levels in the CsA group showed at 3 months (232+/-47 vs 202+/-42 m/dL; P=.0001), 6 months (232+/-49 vs 205+/-41 mg/dL; P=.0001), and 12 months (217+/-50 vs 202+/-40 mg/dL; P=.028), despite receiving a greater proportion of lipid-lowering drugs (49% vs 15%; P=.0001). Logistic regression analysis showed that CsA was an independent predictor of posttransplant hyperlipidemia (OR: 5.8, CI 95%; 3.3-10.7; P=.0001) as were age, female gender, pretransplant dyslipidemia, and body mass index (BMI). Interestingly, an interaction was observed between pretransplant BMI and CIs: Among pretransplant normal weight patients (BMI <25 kg/m2), CsA produced a greater incidence of hyperlipidemia than tacrolimus (58% vs 23%; P=.0001) while not among patients who were overweight (BMI >25 kg/m2: pretransplant 58% vs 42%; P=.341). In conclusion, CsA confers a higher risk of hyperlipidemia after RT in nondiabetic patients, particularly those with normal pretransplant weight.