Efficacy of mycophenolate mofetil combined with topical 0.05%tacrolimus in high-risk keratoplasty:1-year cohort study

AIM:To investigate the efficacy of systemic mycophenolate mofetil(MMF)as an adjunct in combination with topical tacrolimus(FK506)and corticosteroid eyedrops for preventing corneal graft rejection after high-risk keratoplasty(HRK).METHODS:In this cohort study,55 consecutive patients(55 eyes)from an eye center who met the criteria of HRK were included.The definition for HRK includes large grafts of no less than 9 mm diameter,vascularized cornea of two or more quadrants,regrafting,or eccentric grafts.After penetrating keratoplasty,25 patients treated with systemic MMF in combination with 0.05%FK506 and tapering corticosteroid eyedrops were enrolled in Group 1 from October 2019.Thirty patients receiving postoperative treatment with 0.05%FK506 and tapering corticosteroid eyedrops alone were enrolled in Group 2 from January 2018 to September 2019.All participants were closely monitored after surgery,and episodes of graft rejection and relevant clinical data were collected and assessed over a one-year follow-up period.RESULTS:After a follow-up of 9.6±3.2mo,graft rejection episodes occurred in 4 cases(16%)in Group 1 and 18 cases(60%)in Group 2.One reversible and 3 irreversible graft rejections occurred in Group 1,while 3 reversible and 15 irreversible rejections occurred in Group 2.Kaplan-Meier analysis revealed that 82.5%of grafts in Group 1 and 37.1%in Group 2 did not experience corneal graft rejection(P<0.01,log-rank test).The clear graft survival rate was 83.6%in Group 1 and 36.7%in Group 2(P<0.01,log-rank test)within one year of follow-up.No severe systemic side effects were observed in either group during the follow-up period.CONCLUSION:The triple treatment regimen consisting of MMF,topical FK506,and corticosteroid eyedrops represents a promising strategy for effectively preventing graft rejection and improving graft survival in patients with HRK.

Combination treatment with telitacicept,mycophenolate mofetil and glucocorticoids for immunoglobulin A nephropathy:A case report

BACKGROUND Telitacicept reduces B cell activation and abnormal immunoglobulin A(IgA)antibody production by inhibiting the activity of B lymphocyte stimulator(BLyS)and a proliferation-inducing ligand(APRIL),thereby decreasing IgA deposition in the glomeruli and local inflammatory response.This ultimately protects the kidneys from damage.This mechanism suggests that Telitacicept has potential efficacy in the treatment of IgA nephropathy.CASE SUMMARY We present the case of a 24-year-old female who was diagnosed with IgA nephropathy due to significant proteinuria and mild renal impairment.Pathologically,she exhibited focal proliferative glomerulonephritis.Treatment with angiotensin II receptor blocker,hormones,and mycophenolate mofetil did not lead to a significant improvement in her condition.However,upon the addition of telitacicept,the patient’s renal function recovered and her proteinuria rapidly reduced.Hormones were swiftly tapered and discontinued,with no occurrence of severe infections or related complications.CONCLUSION Telitacicept combined with hormones and mycophenolate mofetil may be a safe and effective induction therapy for IgA nephropathy.

The Beneficial Effect of 3-Month-Induction Therapy with Corticosteroids and Mycophenolate Mofetil Followed by Maintenance Therapy with Yearly Rituximab Infusions as Sole Maintenance Therapy in Cryptogenic Chronic Hypersensitivity Pneumonitis

Background: The available data on cryptogenic chronic hypersensitivity pneumonitis (ccHP) indicate an inherited predisposition to disease with triggering autoimmune phenomena. Hence, we evaluated prospectively the role of a new autoimmune regimen in treatment of its severe and progressive disease. Patients and Methods: A total of 9 patients were included in the study. They had criteria for ccHP viz. 1) clinical features of cryptogenic progressive restrictive lung disease, 2) high-resolution computed tomographic pulmonary abnormalities, and 3) bronchoalveolar lavage lymphocytosis (>30%). The regimen consisted of an initial induction phase of 3-month Solumedrol 1 g IV daily for 3 days followed by 1 month of Prednisone (P) 60 mg/day to tapered down to discontinuation by 3rd month. They also had received Mycophenolate mofetil (MMF) 1 g twice daily for 3 months. This stage was followed by a maintenance phase of yearly Rituximab infusions (1 g followed by 1 g 2 weeks later). Results: compared to their previous 6 months deterioration;all patients showed significant improvement in their forced vital volume, diffusion capacity for carbon monoxide, 6-minutes-walk after the induction phase (at 3 months) which improved further at 15 months with Rituximab therapy. Conclusion: After 3-month induction therapy with P and MMF;yearly R treatment is a safe, practical and effective long-term therapy for ccHP.

Effect of Rituximab Versus Mycophenolate Mofetil or Cyclophosphamide as Control in Lupus Nephritis:A Meta-Analysis

Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.

Protective Effect of Mycophenolate Mofetil(MMF) Against Short-term Acute Rejection of Kidney Transplant

To observe the protective effect of MMF against short term(3 months) acute rejection of renal transplantion. 112 patients undergone renal transplantation were randomly divided into two groups: MMF group (2.0 g/d) and azathioprine group. Patients in both groups received cyclosporine A (CsA) and steroid hormone treatment in the same way. In three months time, 10/60 cases in the MMF treated group showed acute rejection with an acute rejection rate of 16.6%. 22/52 patients of the AZA group had acute rejection with a rejection rate of 41.5%. The difference between the two groups is significant (P<0 01). Side effects manifested in MMF group includereduction of blood white cell count and platelet count (5 cases) and diarrhea (3 cases). They resume recovery after reduction of the dosage of or stoppage of MMF. Both hepatic renal functions are not affected. In AZA group, liver function is damaged in 9 patients. MMF is effective in the prevention or reduction of short term acute rejection of transplants. Its side effects are mild and reversible.

Influence of mycophenolate mofetil (MMF) upon thematuration and allo-stimulatory activity of cultured progenitors of dendritic cells and the effectson the tolerance induction in allograft recipients

To investigate the influence of mycophenolate mofetil (MMF) upon the maturation and the allo-stimulatory activity of cultured progenitors of dendritic cells (DCp), and to evaluate the effects of the pre-treated dentritic cells of recipients with MMF on the tolerance induction as well as its possible mechanism, GM-CSF and MMF were added to the in vitro cultured progenitor cells, and the immuno-phenotypical analysis was performed by means of flow cytometry. The secretion of IL-12 was detected by ELISA and the stimulatory activities of DCp on allogeneic T cells were observed by mixed lymphocyte reaction. Twenty-four C57BL/6 mice were divided into 3 groups (each with 8 mice), in which group A of mice accepted allografts of heart from BALB/c mice, group B of mice had received untreated DCp from donors of BALB/c mice 7 days before transplantation, and C57BL/6 mice in group C were treated by injection with MMF-treated allografts of heart from BALB/c mice 7 days before transplantation. The survival times of allografts and the changes of the cytokine levels in sera of the recipient mice were observed after transplantation. The experimental results showed that MMF could significantly inhibit the expressions of the co-stimulatory molecules CD80 and CD86 on DCs and the secretion of IL-12 and the allo-stimulatory activities of DCs were also markedly inhibited. The survival times of allografts in group B of mice were longer than those in group A, while the group C showed the longest survival times of allografts, with a marked reduction in the production of the Th1 type cytokines. It is evident that MMF has a suppressive effect on the maturation and allo-stimulatory activities of the cultured dendritic cell progenitors, thus leading to a donor specific tolerance in heart-transplanted recipients.

Effects of Mycophenolate Mofetil on Renal Interstitial Fibrosis after Unilateral Ureteral Obstruction in Rats

To investigate the effects of mycophenolate mofetil (MMF) on the process of renal interstitial fibrosis,unilateral ureteral obstruction (UUO) model was established in rats Twenty Sprague-Dawley rats underwent UUO and received vehicle ( n =10) or MMF (20 mg kg -1 d -1 , by daily gastric gavage, n= 10) during a period of 5 days following surgery, and the additional 10 rats were served as sham-operated group The rats were killed 5 days after surgery Immunohistochemistry was performed on renal tissue for proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (α-SMA) and type Ⅰ and Ⅲ collagen (colⅠ, colⅢ) Histological studies were also done by MASSON staining Five days after surgery, proliferating cells in tubules, interstitium as well as interstitial myofibroblast (MyoF) infiltration and interstitial colⅠ, colⅢ deposition were all significantly reduced by MMF treatment MMF also alleviated the histological changes of UUO rats These results suggested that the reduction of interstitial MyoF infiltration may be an important event by which MMF prevents renal injury caused by UUO and MMF could be used to limit the progression of renal fibrosis

Effects of mycophenolate mofetil vs cyclosporine administration on graft survival and function after islet allotransplantation in diabetic rats

AIM: To develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single agent. METHODS: Thirty-six male Wistar rats and 18 male Lewis rats were used as recipients and donors respectively. Diabetes was induced by the use of streptozotocin (60 mg/kg) intraperitoneally. Unpurified islets were isolated using the collagenase digestion technique and transplanted into the splenic parenchyma. The recipients were randomly assigned to one of the following three groups: group A (control group) had no immunosuppression; group B received cyclosporine (CsA) (5 mg/kg); group C receivedmycophenolate mofetil (MMF) (20 mg/kg). The animalswere killed on the 12th d. Blood and grafted tissues were obtained for laboratory and histological assessment. RESULTS: Median allograft survival was significantly higher in the two therapy groups than that in the controls (10 and 12 d for CsA and MMF respectively vs 0 d for the control group, P＜0.01). No difference in allograft survival between the CsA and MMF groups was found. However,MMF had less renal and hepatic toxicity and allowed weight gain.CONCLUSION: Monotherapy with MMF for immunosu ppression was safe in an experimental model of islet allotransplantation and was equally effective with cyclosporine, with less toxicity.

Mycophenolate mofetil for drug-induced vanishing bile duct syndrome

Amoxicillin/clavulanate is associated with liver injury, mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment, but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.

Effect of low-dose tacrolimus with mycophenolate mofetil on renal function following liver transplantation

AIM: To determine whether low-dose tacrolimus (TAC) combined with mycophenolate mofetil (MMF) is a safe approach to decrease the incidence of chronic kidney disease (CKD) in liver transplantation (LT) recipients. METHODS: We analyzed the medical records of 689 patients who underwent LT between March 1999 and December 2012 in a single Chinese center. Immunosuppression was initiated with a calcineurin inhibitor (TAC or CSA) and prednisone with or without MMF. CKD is defined by the glomerular filtration rate (GFR), estimated by an abbreviated Modification of Diet in Renal Disease formula, < 60 mL/min per 1.73 m(2) for at least 3 consecutive months after LT. Individuals with TAC trough concentrations <= 8 ng/mL at 3 mo after LT were defined as the low-dose group. The incidence of CKD within 5 years was compared between the TAC group and the CSA group, as well as between four subgroups (low-dose and high-dose TAC groups with or without MMF). RESULTS: No difference regarding the occurrence of pre-LT renal dysfunction or that of post-LT rejection was found between the TAC and CSA groups or between the four subgroups. With a definition of GFR < 60 mL/min per 1.73 m(2), the overall incidence of CKD was significantly higher in the CSA group than in the TAC group. The incidence of CKD in the low-dose TAC + MMF group (7.7%) was significantly lower than that observed in the low-dose TAC group (15.9%), high-dose TAC group (24.6%) and high-dose TAC + MMF group (18.5%). The cumulative 1-, 3- and 5-year incidence rates of CKD were 12.7%, 14.5% and 16.7%, respectively. The cumulative 5-year survival rates were 61.7% and 82.2% in patients with or without CKD, respectively. CONCLUSION: In LT patients, the choice of immunosuppressive therapy appears to affect renal function and patient survival. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Cyclosporine A, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro

AIM： To investigate the effect of cyclosporine A （CsA）, FK-506, and mycophenolate mofetil （MMF） and 40-0-[2- hydroxyethyl]rapamycin （RAD） on proliferation of human intrahepatic biliary epithelial cells （BECs） in vitro.METHODS： BECs were isolated from six human liver tissuespecimens with the immunomagnetic separation method and treated with different concentrations of CsA, FK-S06, RAD, and MMF in vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after treatment, respectively. One-way analysis of variance was used to analyze the results. Expression of CK 19 in BECs was monitored by flow cytometry and Western blot.RESULTS： Six lines of BECs were established. They survived for 4-18 wk in vitro. Flow cytometry analysis showed that these cells always expressed CK19. CsA, FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit proliferation of BECs （P〈0.05） was 500, 100, 0.25, and 100 pg/L, respectively. However, the expression of CK19 by BECs was not changed.CONCLUSION： CsA, FK-506, RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in vitro, while RAD has the strongest growth-inhibitory effect. Their possible effects on liver regeneration and bile duct injury in transplant patients should be further investigated.

Effect of mycophenolate mofetil plus adriamycin on HepG-2 cells

AIM:To investigate the influence of mycophenolate mofetil(MMF)plus adriamycin(ADM)on hepatocellular carcinoma(HCC)cells. METHODS:HCC cells were treated with 100μg/ml of MMF alone(MMF group),1μg/mL of adriamycin(ADM group)alone,or a combination of the drugs(MMF+ ADM group).We performed an 3-[4,5-dimethylthiazol2-yl]-2,5-diphenyl tetrazolium bromide(MTT)assay to measure the growth inhibition rate of HCC cells.Flow cytometry was used to determine the percentage of cells in different phases of the cell cycle and the number of apoptotic cells.Hoechst 33258 staining revealed the morphological changes associated with apoptosis in HCC cells. RESULTS:The results of MTT assays revealed that monotherapy with ADM or MMF showed inhibition of cell growth,while MMF+ADM therapy afforded an inhibition rate of more than 90%with cell distribution in G1 and G2/M phase greater than that in S phase. MMF+ADM treatment also downregulated Bcl-2 expression markedly.The growth of HCC cells was markedly inhibited and apoptosis was enhanced in all the 3 groups.Compared with other 2 groups,the MMF +ADM group showed more obvious apoptosis of cells. CONCLUSION:The MMF plus ADM combination exerts remarkable inhibitory effects on the growth of HCC cells.

Mycophenolate mofetil for maintenance of remission in steroid-dependent autoimmune pancreatitis

Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis;however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.

Inhibitory effect of mycophenolate mofetil on human hepatocellular carcinoma cell line HepG-2

To investigate the inhibitory effect of mycophenolate mofetil on human hepatocellular carcinoma cell line HepG-2. Methods： HepG-2 cells were cultured in the presence of the different concentrations of mycophenolate mofetil in vitro. MTT assay was used to analyze the inhibition of cell viability conferred by mycophenolate mofetil. Cell apoptosis was observed using Hoechst33258 staining, and the percentage of HepG-2 cells at different cell cycles was determined through flow cytometry. The ability of cell adhesion was evaluated by in vitro adhesion assay. Gene expressions of factors （ICAM-1 and VCAM-1） were detected by RT-PCR. Results： Mycophenolate mofetil significantly inhibited the growth of HepG-2 cells by inducing the apoptosis of cells and this drug also inhibited the adhesion of HepG-2 cells in a dose-dependent manner. Marked morphological changes characterized in cell apoptosis were demonstrated through Hoechst33258 staining. In addition, mycophenolate mofetil decreased the proportion of S phase cells and increased that of G0/G1 phase cells. [^3H]-Thymidine uptake assay indicated that the application of mycophenolate mofetil at different concentrations significantly inhibited the cell proliferation. RT-PCR identified the expression levels of ICAM-1 and VCAM-1 genes in liver cancer cells after cultured for 72 h with different concentrations of drug. An inverse relationship was found between the expressions of ICAM-1 and VCAM-1 and drug concentrations. Conclusion： Mycophenolate mofetil has remarkable inhibitory effect on hepatocarcinoma HepG-2 cells.

Eco-friendly reduced graphene oxide for the determination of mycophenolate mofetil in pharmaceutical formulations

Graphene oxide(GO) was synthesized and characterized by scanning electron microscopy(SEM), energy dispersive X-ray spectroscopy(EDX), atomic force microscopy(AFM), X-ray diffraction(XRD), Fourier transform-infrared spectroscopy(FT-IR) and thermogravimetric analysis(TGA). GO was then electrochemically reduced and used for electrochemical study of mycophenolate mofetil(MMF). The electrochemically reduced graphene oxide(ERGO) film on glassy carbon electrode(GCE) showed enhanced peak current for electrooxidation of MMF. MMF exhibited two irreversible oxidation peaks at 0.84 V(peak a_1)and 1.1 V(peak a_2). Effects of accumulation time, pH and scan rate were studied and various electrochemical parameters were calculated. A differential pulse voltammetric method was developed for the determination of MMF in bulk samples and pharmaceutical formulations. Linear relationship was observed between the peak current and concentration of MMF in the range of 40 nM–15 μM with a limit of detection of 11.3 nM. The proposed method is simple, sensitive and inexpensive and, hence, could be readily adopted in clinical and quality control laboratories.

TWO-YEAR OBSERVATION OF A RANDOMIZED TRIAL ON TACROLIMUS-BASED THERAPY WITH WITHDRAWAL OF STEROIDS OR MYCOPHENOLATE MOFETIL AFTER RENAL TRANSPLANTATION

Objective To evaluate the safety and feasibility of steroid or mycophenolate mofetil （MMF） withdrawal from tacrolimus-based immunosuppressant regimen in renal allograft recipients. Methods A cohort of 45 patients following cadaveric renal allograft transplantation were randomly divided into 3 groups based on the regimen of combination of tacrolimus, steroid, and MMF： triple therapy group, steroid withdrawal group, and MMF withdrawal group. During 2 years, survival of patients and allografts, clinical acute rejection, adverse events, hepatic and renal allograft function, and blood lipids were monitored to evaluate the safety and feasibility of steroid or MMF withdrawal after renal transplantation. Results During two-year observation, steroid or MMF was successfully withdrawn from immunosuppressant regimen based on tacrolimus without any clinical acute rejection renal allografts kept excellent function. Some adverse events among groups. Patient and graft survival rates were 100% and all the occurred and there were no significant differences Conclusion Withdrawal of steroid or MMF in low-immunological-risk renal allografts treated with tacrolimus-based immunosuppressant regimen can be achieved with no increased risk of acute rejection.

Correlation of abnormal histology with endoscopic findings among mycophenolate mofetil treated patients

To describe all abnormal histological findings and their associated endoscopic presentation in patients using mycophenolate mofetil (MMF). METHODSA retrospective review of all individuals prescribed MMF within 6 mo of a colonoscopy or flexible sigmoidoscopy between 07/2009 and 09/2015 was performed within Northwell Health system. Records were analyzed for age, gender, procedure indication, MMF indication, and both gross and microscopic findings. Only reports with abnormal histology were included. RESULTSOne hundred and eighty-four procedures from 170 patients were found, of which 39 met inclusion criteria. Fifty-one point three percent were female. MMF was used for solid organ transplant in 71.8%. Diarrhea was the indication for 71.8% of colonoscopies. Fifty-nine percent of reports revealed gross and microscopic abnormalities while 41.0% had only microscopic findings. Only 11 patients’ reports (28.2%) indicated a specific histopathology of MMF colitis. Among the entire group, only 23.1% of abnormal histology was isolated proximal to the splenic flexure. CONCLUSIONOur results demonstrate a high rate of left sided disease and microscopic findings without gross mucosal abnormalities among patients using MMF. Also, a broader definition of MMF-colonopathy may be appropriate, with a majority of our abnormal histology falling outside of the more narrowly defined MMF-colitis category. Given the high frequency of isolated microscopic abnormalities and distal disease, sigmoidoscopy with random biopsies may be an appropriate, less invasive initial endoscopic examination in selected MMF patients.

Safety and Efficacy of Once-Daily Administration of Mycophenolate Mofetil in Kidney Transplant Patients—A New Treatment Option for Non-Adherence

Non-adherence to immunosuppressive therapy is associated with reduced graft survival. Fifteen long-term follow up kidney transplant patients with stable post-transplant clinical courses were enrolled in the study. All patients were prescribed to tacrolimus prolonged release, mycophenolate mofetil (MMF) and corticosteroid at the time of enrolment. Twice-daily administration of MMF was then converted to a single daily dose. As a result, all immunosuppressive agents were administered simultaneously at one time in the morning. The daily total doses of the three immunosuppressants were identical during the study period. No acute rejection or adverse event was observed during the study period. Blood urea nitrogen and estimated glomerular filtration rate did not change significantly after conversion to once-daily administration. The blood tacrolimus trough level and the Mycophenolic acid (MPA) trough level also did not change significantly after conversion to once-daily administration. Interestingly, the meanmedian MPA trough level remained >3 μg/ml even after conversion to once-daily administration. A sufficient plasma MPA level was maintained after conversion to once-daily administration, and no acute rejection was observed during the study period. To our knowledge, this study is the first to report that the plasma MPA concentration can be maintained after once-daily administration of MMF in long-term kidney transplant patients. Once-daily administration of immunosuppressive agents may improve long-term graft survival because of better treatment adherence due to the reduced dosing frequency. The safety or efficacy of conversion to once-daily administration of MMF should be evaluated in a future randomized controlled large-scale clinical study.

Mycophenolate mofetil toxicity mimicking acute cellular rejection in a small intestinal transplant

Mycophenolate mofetil(MMF) is an important medication used for maintenance immunosuppression in solid organ transplants. A common gastrointestinal(GI) side effect of MMF is enterocolitis, which has been associated with multiple histological features. There is little data in the literature describing the histological effects of MMF in small intestinal transplant(SIT) recipients. We present a case of MMF toxicity in a SIT recipient, with histological changes in the donor ileum mimicking persistent acute cellular rejection(ACR). Concurrent biopsies of the patient's native colon showed similar changes to those from the donor small bowel, suggesting a non-graft specific process, raising suspicion for MMF toxicity. The MMF was discontinued and complete resolution of these changes occurred over three weeks. MMF toxicity should therefore be considered as a differential diagnosis for ACR and graftversus-host disease in SITs.

The role of mycophenolate in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis

Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis of guanosine nucleotides leading to selective inhibition of lymphocyte proliferation. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Since the course of disease of AAV usually requires long term immunosuppression, mycophenolate has been explored as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate is a potent immunosuppressive agent in the therapy of AAV, non-inferior to other available drugs with comparable side effect profile. Therefore, it could be a valuable alternative in cases of toxicity with life threatening side effects or intolerance to cyclophosphamide or azathioprine, in cases with high cumulative dose of cyclophosphamide, but also in cases with insufficient response. Several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects that raises concerns about its usefulness in the treatment of AAV. This review describes the efficacy of mycophenolate in AAV as remission induction agent, as remission maintenance agent, and as therapeutic option in relapsing AAV disease, the relapse rate following discontinuation of mycophenolate, and the adverse events related to mycophenolate treatment.