A new acute inflammatory syndrome related to the introduction of mycophenolate mofetil in patients with Wegener's granulomatosis.

Mycophenolate mofetil (MMF) is increasingly used for prevention of allograft rejection and to treat immune disorders. We report the development of an acute inflammatory syndrome in two patients with Wegener's granulomatosis after MMF was introduced, because of persistent renal and systemic disease activity despite cyclophosphamide treatment. Within 1 week both patients developed an acute inflammatory syndrome, characterized by fever, arthralgias and muscle pain. No infection could be detected and no indications for increased Wegener's activity were present. MMF was stopped resulting in a rapid and complete resolution of the syndrome. A rechallenge with 2 g of MMF in the second patient resulted in a relapse of the syndrome within 4 days. There was an association between symptoms and increased levels of mycophenolic acid (MPA) acyl glucuronide and serum interleukin-6, suggesting the induction of inflammatory cytokines by MPA acyl glucuronide as the cause of the syndrome. Therefore, special attention should be given to side effects such as fever, arthralgias and muscle pain when treating patients with Wegener's granulomatosis during the active phase. Because this side effect of MMF may also occur after solid organ transplantation and in other immune disorders, pharmacokinetic profiling of MPA and MPA acyl glucuronide is needed in future studies with MMF.     

Sirolimus: A Switch Option for Mycophenolate Mofetil–Induced Leukopenia in Renal Transplant Recipients

Mycophenolate mofetil (MMF) is a potent immunosuppressive agent used to prevent acute and chronic rejection in kidney transplantation or for rescue therapy. One side effect of MMF is bone marrow toxicity, including leukopenia, which may necessitate drug withdrawal. We report 2 patients who underwent kidney transplantation and developed leukopenia while receiving MMF and safely switched to sirolimus. A 35-year-old woman underwent deceased donor kidney transplantation. She received basiliximab, tacrolimus, MMF, and a corticosteroid. On postoperative day (POD) 75, her white blood cell (WBC) count was 1800/μL. A 44-year-old women underwent deceased donor kidney transplantation and received basiliximab, tacrolimus, MMF, valganciclovir, and a corticosteroid. On POD 88, her WBC count was 1320/μL. MMF was switched to sirolimus, resulting in recovery of WBC count without rejection. Switch from MMF to sirolimus is safe and favorable in MMF-induced leukopenia in renal transplant recipient.     

A Case of Coloboma in a Newborn to a Woman Taking Mycophenolate Mofetil in Pregnancy After Kidney Transplantation

Recently, mycophenolate mofetil (MMF) has been introduced in the immunosuppressive strategy after kidney transplantation. Recently, the existence of a MMF associated embriopathy has been hypothesized, namely, multiple craniofacial malformations. Only 1 report has described chorioretinal coloboma.We report a case of woman who used MMF throughout pregnancy after kidney transplantation. Her newborn developed coloboma of the right eye associated with an ocular cyst without any other malformation. The other drugs used by our patient are not considered teratogenic. Therefore, it seems reasonable to conclude a causal relationship between MMF and the malformation observed in this newborn.     

A Multiplex Bead Array Analysis to Monitor Donor-Specific Cytokine Responses After Withdrawal of Immunosuppression in HLA-Identical living Related Kidney Transplant Patients

Immune reactivity after HLA-identical living related (LR) kidney transplantation can be caused by minor histocompatibility antigen and non-HLA antigen mismatches between donor and recipient. In our center, HLA-identical LR kidney transplant recipients receive azathioprine (AZA) or mycophenolate mofetil (MMF) in combination with corticosteroids for 1 year after transplantation. Thereafter, AZA or MMF was withdrawn, and the patients were treated with steroid monotherapy as maintenance therapy. We questioned whether withdrawal of AZA or MMF affected the donor-specific lymphocyte proliferation and cytokine production. Donor and third-party T-cell reactivities were determined by mixed lymphocyte reactions and by cytokine production using multiplex bead array technique. The donor and third-party proliferative capacities were not affected after withdrawal of AZA or MMF. Thirteen of 17 cytokines were detected by the multiplex bead array technique. No differences were observed after third-party induced cytokine production after withdrawal of AZA or MMF. However, production of donor-specific interferon-γ and macrophage inflammatory protein-1β increased after discontinuation of AZA or MMF, but no clinically relevant acute rejection was observed. In conclusion, after HLA-identical LR kidney transplantation, donor-specific cytokine responses can be found when AZA or MMF therapy is discontinued. The clinical relevance of this phenomenon is still not evident.     

Recurrent membranoproliferative glomerulonephritis type 1 in successive renal transplants

We report a man who developed renal failure due to membranoproliferative glomerulonephritis (MPGN) type 1 which recurred in two cadaveric kidney transplants. This is the third such case in the literature. Nephrotic syndrome developed within 1 month following transplantation and histologic evidence of disease recurrence was documented in both kidneys 2 months after transplantation. Both grafts failed within 18 months. Factors which determine disease recurrence remain obscure.     

Kidney Transplant from the Same Donor without Maintenance Immunosuppression after Previous Hematopoietic Stem Cell Transplant

In January 2005, an 18‐year‐old male patient with acute myeloid leukemia (AML) received a haploidentical hematopoietic stem cell transplantation (HSCT) from his father. He developed hemolytic uremic syndrome and end‐stage renal disease (ESRD) requiring hemodialysis on day 357 after HSCT. On day 1020 after HSCT, a living kidney donation from the stem cell donor was carried out. The creatinine before kidney transplantation (KT) was ≈450 μmol/L, 268 μmol/L on day 2 after KT, 88 μM on day 38 and 89 μmol/L on day 960 (day 1980 after HSCT). Immunosuppression was gradually discontinued: cortisone on day 28, tacrolimus on day 32 and MMF on day 100 after KT (day 1120 after HSCT). As of June 2010, 66 months after HSCT and 32 months after KT, the patient has had neither rejection episodes nor clinical manifestations of transplantation‐related complications. The patient reached 100% hematopoietic donor chimerism prekidney transplant and retained this state postkidney transplant. This unique case is the first report of a successful kidney transplant without immunosuppression after HSCT from the same haploidentical donor.     

Impact of mycophenolate mofetil on recurrent rejection in kidney transplant patients

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

Two cases of calcineurin inhibitor-associated reversible posterior leukoencephalopathy syndrome in renal transplant recipients

Reversible posterior leukoencephalopathy syndrome (RPLS) is one of the important side effects of calcineurin inhibitors (CNIs). Magnetic resonance imaging (MRI) of the brain is useful for the diagnosis of RPLS, showing the edema primarily in the cortex and subcortical white matter of the posterior brain regions. Interruption of CNIs is essential for the treatment of patients with RPLS. Herein we have described 2 cases (1.7%) of RPLS induced by CNIs after kidney transplantation. The first case was a 56-year-old man with chronic renal failure due to diabetic nephropathy who received a living-related kidney transplantation in 2006. Initial immunosuppressive therapy consisted of cyclosporine, mycophenolate mofetil (MMF), prednisolone, and basiliximab. Four months after transplantation, he developed unconsciousness and paralysis. The second case was a 24-year-old woman with end-stage renal disease due to Alport syndrome who received an ABO-incompatible living-related kidney transplantation. Initial immunosuppressive therapy consisted of tacrolimus, MMF, prednisolone, and basiliximab. On postoperative day 3, she developed convulsions and unconsciousness. In both patients, RPLS was diagnosed with neurological symptoms and MRI findings at early stage of the disease, and they recovered rapidly from the disease by the interruption of CNIs. Our data demonstrated that early diagnosis and immediate interruption of CNIs were essential for the treatment of RPLS after kidney transplantation.     

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

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

雷公藤多苷对移植肾长期存活率的影响

目的:探讨雷公藤多苷(TW)作为免疫抑制剂对肾移植患者长期存活率的疗效及副作用.方法:104例患者在肾移植术后采用TW 泼尼松(Pred) 环孢霉素(GsA) 硫唑嘌呤(AZa)免疫抑制剂治疗,48例患者在肾移植术后采用Pred GsA 骁悉(MMF)免疫抑制剂治疗,就以下方面对两组患者进行观察比较:(1)术后5年内发生排斥反应及临界改变情况;(2)外周血白细胞下降、肝功能异常的发生率;(3)严重感染情况;(4)出现尿蛋白情况;(5)术后5年内肾功能变化情况及移植肾5年存活率.结果:5年内AZa TW组急性排斥反应及临界改变的发生率较MMF组低,分别为11.5%、16.7%和4.8%、6.3%(P＞0.05);GPT高于正常的发生率分别为7.7%、16.6%(P＞0.05);外周血白细胞低于正常的发生率分别为0.96%、18.8%(P＜0.01);严重感染的发生率分别为1.9%、18.8%(P＜0.05),5年内出现蛋白尿的患者例数分别为17.3%、29.2%(P＞0.05),两组移植肾5年存活率相似,分别为89.6%、85.4%(P＞0.05).结论:在肾移植术后应用CsA Pred AZa TW免疫抑制方案是可行的,既可以使肾移植术后急性排斥反应减少,同时还能减少蛋白尿及慢性排斥反应的发生率下降,为国内提高移植肾长期存活率提供了一条新的途径.     

Late developing C4d-positive humoral renal allograft rejection associated with withdrawal of mycophenolate mofetil

In renal transplantation, C4d-positive acute humoral rejection (AHR) usually develops in the early stage posttransplantation. It is clear C4d can be detected late after the operation, when it is associated with chronic renal allograft rejection. We report a case of a renal allograft recipient who experienced C4d-positive acute renal allograft rejection associated with withdrawal of mycophenolate mofetil (MMF) at 10 months after transplantation. This 21-year-old single male patient received his first cadaveric renal allograft under immunosuppression with cyclosporine, MMF, and prednisolone. The serum creatinine recovered to the normal range within 4 days. A protocol biopsy performed at 1 month after transplantation revealed no signs of rejection. The graft function was stable until 10 months postoperation, when MMF was converted to mizoribin. Three days later a biopsy showed a C4d-positive rejection. Patient had no response to the MMF combined with tacrolimus and steroid bolus therapy, which generally improves 85% of AHR among Chinese. He finally returned to dialysis. Our report suggested that C4d positive AHR may occur late after transplantation. MMF is important to suppress the body's humoral response to allograft; when MMF was converted to a weaker immunosuppressant, the dose of the other immunosuppressants (cyclosporine for example) must be adjusted properly.     

Acute Inflammatory Syndrome Paradoxically Induced by De Novo Purine Inhibitors Synthesis Before Renal Transplantation: A Case Report and Review of the Literature

Background

Mycophenolate mofetil (MMF) and mizoribine (MZR) are increasingly used as immunosuppressive agents for organ transplantation and chronic inflammation. We report a patient with rheumatoid arthritis who had an acute inflammatory syndrome triggered by preoperative immunosuppression therapy with both MMF and MZR.

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

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

Comparison of transplanted kidney function in patients on two different doses of mycophenolate mofetil

INTRODUCTION: Mycophenolate mofetil (MMF), an immunosuppressant that is widely used in renal transplant recipients, is associated with several dose-dependent hematologic and gastrointestinal side effects that lead to drug dose reduction or even discontinuation. The aim of this study was to compare the renal function and acute rejection rates of kidney allograft recipients who were on two different mycophenolate mofetil doses. METHODS: In a prospective study, 59 allograft kidney recipients who were on MMF 2 g/d were randomly selected and followed for evidences of acute rejection or drug side effects. Four patients were excluded from the study due to noncompliance, graft loss, and patient loss from opportunistic infection. Of the remaining 55 patients, 22 patients (40%) underwent MMF dose reduction to 1.35 +/- 0.23 g/d due to perceived side effects or economic reasons (group 1). The mean time for this change was 4.2 +/- 2.1 months after the kidney transplantation. The remaining patients (group 2, n = 33, 60%) had no change in MMF 2 g/d drug dosage. All patients were followed for at least 30 months after transplantation. Renal function tests (blood urea and serum creatinine) were measured monthly. Statistical analysis was performed using SPSS 11.0 (Student t test). A P value < .05 was considered significant. RESULTS: The two groups were comparable regarding age, gender, other immunosuppressive medications, and the time after transplantation. There were no episodes of acute rejection in group 1 after MMF dose reduction. The renal function (blood urea or serum creatinine levels) was comparable between the two groups at the end of study (P = .846 and .610, respectively). CONCLUSION: MMF dose reduction was not associated with an increased risk of acute renal allograft rejection or impaired graft function.     

Long-term outcome of sirolimus rescue in kidney-pancreas transplantation

Sirolimus (SRL) rescue in kidney-pancreas transplantation has not been well described. We reviewed 112 KPTxs performed at our institution between December 3, 1995 and June 27, 2002. All patients received antibody induction, tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. In 35 patients, SRL was substituted for MMF for the following reasons: acute rejection (AR) of kidney or pancreas despite adequate TAC levels, MMF intolerance, increasing creatinine levels, and TAC-induced hyperglycemia. Three-year kidney and pancreas graft survivals were 97% and 90%, respectively. Of 10 patients who were switched to SRL because of AR, one kidney failed because of antibody-resistant AR, and one kidney developed borderline AR; the other eight patients remain AR-free. AR developed in seven other patients despite therapeutic SRL levels; six had TAC levels less than 4.5 ng/mL. The mean creatinine levels overall and for the group with increasing creatinine remained stable. All patients who were switched to SRL for TAC-induced hyperglycemia or MMF intolerance improved. Kidney-pancreas transplant recipients can be safely switched to SRL with excellent graft and patient survival.     

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.     

Belatacept treatment for two yr after liver transplantation is not associated with operational tolerance

Belatacept was recently evaluated in liver transplantation (LT) in a phase II multicenter trial, which was terminated prematurely. Patients were more than two yr post‐LT at the time. As high rates of spontaneous tolerance after LT have been reported and as belatacept has marked immunomodulatory effects, we decided to maintain the belatacept patients enrolled at our center (n = 4) on MMF monotherapy. All belatacept patients on MMF monotherapy developed graft dysfunction consistent with acute rejection after a mean period of 10.3 (7–14) wk. Patients were therefore switched to triple therapy with CNI, MMF, and corticosteroids. Graft dysfunction resolved within 1–3 wk after switch. At the time of belatacept discontinuation, mean eGFR was 105.1 mL/min/1.73 m² (92.1–118.9) in belatacept patients compared to 58 mL/min/1.73 m² (36.1–98.2) in controls (p = 0.022). One yr after the switch to CNI therapy, eGFR had declined by 27.4 mL (19.2–39.3; p = 0.008). Thus, LT patients treated with belatacept show superior kidney function that declines upon institution of CNIs. MMF monotherapy following withdrawal of belatacept is associated with a high incidence of graft dysfunction. Belatacept has no obvious immunomodulatory effects in LT recipients that would be sufficient to allow drug withdrawal with a high rate of success.     

肾移植术后早期无尿或少尿的诊治(附66例报告)

目的:探讨肾移植术后早期无尿或少尿的原因及诊治方法.方法:回顾性分析66例肾移植术后早期无尿或少尿患者的发生情况.并分别应用以FK506或CsA为主的免疫抑制剂(FK506/CA+MMF+Pred)等综合治疗方案.结果:66例肾移植术后早期无尿或少尿的主要原因是急性肾小管坏死(77.27%),其次是急性排斥反应(10.61%),其中有2例移植肾原发无功能和移植肾破裂、肾动脉栓塞各1例术后切除移植肾.FK506组的34例移植肾功能在术后5～35天内均恢复正常,CsA组有1例因急性排斥反应合并严重肺部感染而死亡,24例移植肾功能在术后7～48天内均恢复正常,3例血肌酐在142～215 μmol/L之间.结论:肾移植术后早期出现无尿或少尿后应及时分析原因,并给予相应的综合治疗.FK506+MMF+Pred的三联免疫治疗有助于移植肾功能的早期恢复.     

Posterior Reversible Encephalopathy Syndrome Independently Associated With Tacrolimus and Sirolimus After Multivisceral Transplantation

Posterior reversible encephalopathy syndrome (PRES) is a small vessel microangiopathy of the cerebral vasculature that occurs in 0.5–5% of solid organ transplant recipients, most commonly associated with tacrolimus (Tac). Clinical manifestations include hypertension and neurologic symptoms. We report an adult multivisceral transplant recipient who experienced recurrent PRES initially associated with Tac and subsequently with sirolimus. A 49‐year‐old woman with short bowel syndrome underwent multivisceral transplantation due to total parenteral nutrition–related liver disease. She was initially maintained on Tac, mycophenalate mofetil (MMF) and prednisone. Three months after transplantation, she developed renal dysfunction, leading to a reduction in Tac and the addition of sirolimus. Eight months after transplantation, she developed PRES. Tac was discontinued and PRES resolved. Sirolimus was increased to maintain trough levels of 12–15 ng/mL. Fourteen months after transplant, she experienced recurrent PRES which resolved after discontinuing sirolimus. Currently 3 years posttransplant, she is maintained on cyclosporine, MMF and prednisone with no PRES recurrence. In addition to calcineurin inhibitors, sirolimus may also be associated with PRES after solid organ transplantation. Ours is the first report of sirolimus‐associated PRES in the setting of multivisceral transplantation. Identifying a safe alternative immunosuppression regimen was challenging but ultimately successful.     

Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years

BACKGROUND: A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years. METHODS: Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. RESULTS: The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. CONCLUSIONS: All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.