Introduction Of Mycophenolate Mofetil Research Articles

Retrospective Cross-Sectional Study Reviewing the Effectiveness of Mycophenolate Mofetil on Saudi Children With Nephrotic Syndrome.

Background Idiopathic nephrotic syndrome (INS) is the most common form of nephrotic syndrome (NS) in children. It is often associated with minimal change disease (MCD). Corticosteroid therapy is the initial treatment, but many patients experience relapses, leading to steroid-dependent nephrotic syndrome (SDNS) or frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). To avoid prolonged steroid use, mycophenolate mofetil (MMF) is used as an immunosuppressive alternative. MMF is safe and effective for treating SDNS and FR-SSNS in children, with studies showing reduced relapse rates. The current study aims to evaluate MMF's effectiveness and safety in Saudi children with NS and identify factors that affect its efficacy. Methods A retrospective cross-sectional study was conducted at King Abdullah Specialized Children's Hospital (KASCH) in Riyadh, Saudi Arabia. The study included children aged one to 14 years diagnosed with NS who received MMF therapy. Data were collected from medical records from 2000 to 2020. Ethical considerations were followed, and statistical analysis was performed using IBM SPSS Statistics for Windows, version 25 (released 2017; IBM Corp., Armonk, New York, United States). Baseline characteristics and responsiveness to MMF were examined. Results In our study, 45 participants (25 males, 20 females) with NS were treated with MMF. Most participants were steroid-dependent (84.44%) and had frequent relapses. MMF was effective in 84.4% of cases, with a significant reduction in relapse; the mean number of relapses decreased from 3.5 before MMF to 1.6 after MMF (p-value = 0.00002). Moreover, 40% of the participants were completely free of relapse after the introduction of MMF. The average duration of the MMF therapy was 45 months. Post-MMF side effects were rare but documented. Gastrointestinal symptoms were extremely rare. Elevated liver enzyme levels were reported in 8.88% (four cases) of the participants. Leukopenia, a more common adverse effect, was reported in 26.66% of cases during the MMF therapy. The average daily dose of steroid was reduced from 12.5 mg/day pre MMF to 2 mg/day post MMF with a p-value of 0.00229. Conclusion Our study evaluated the use of MMF in 45 participants with NS. We found that MMF was effective in 84.4% of cases, leading to a significant reduction in the number of relapses. Post-MMF side effects were relatively rare, except for leukopenia that was reported in 26.66%. In addition, the average rate of reduction of steroid exposure before and after MMF was significant. These findings suggest that MMF is a promising treatment option for children with NS and an alternative therapy to long-term steroid use, due to its safety and effectiveness, although close monitoring for potential side effects is essential.

Long-term outcome of Japanese children with complicated minimal change nephrotic syndrome treated with mycophenolate mofetil after cyclosporine.

Although recent studies have shown that more than half of children with steroid-dependent nephrotic syndrome (SDNS) may continue to have active disease beyond childhood, the long-term outcome in this cohort treated with mycophenolate mofetil (MMF) after cyclosporine remains unknown, particularly in adulthood. We conducted a retrospective study of 44 adult patients (median age, 22.3years) who received MMF for complicated SDNS (median age at MMF initiation, 13.3years) at a single center. Complicated SDNS was defined as the case continuing to relapse after cyclosporine (CsA) treatment. When patients experienced relapses despite MMF initiation, they additionally received a rituximab infusion. The primary endpoint was the probability of achieving treatment-free remission for > 2years. Prior to MMF initiation, all patients received CsA for a median of 46months and 19 received the 12-week cyclophosphamide. After switching from CsA to MMF, only four patients did not relapse during a median follow-up period of 9.6years. At the last visit, only 15 of the 44 patients achieved treatment-free sustained remission. Multivariate analysis revealed that young age (< 6years) at onset of nephrotic syndrome (odds ratio, 11.3) and the experience of steroid dependency during initial CsA treatment (odds ratio, 29.8) were the independent risk factors of active disease into adulthood after MMF initiation. Although none developed renal insufficiency and severe adverse effects of therapy, the introduction of MMF after CsA treatment may not be necessarily associated with improved long-term outcome of children with complicated SDNS.

Efficacy of Mycophenolate Mofetil as a Remission Maintaining Agent in Idiopathic Childhood Nephrotic Syndrome.

Of all cases of idiopathic steroid-sensitive nephrotic syndrome (NS) in children, 40%–75% cases need long-term continuous steroids and/or other immunosuppressants to maintain remission, the effects of which on growth and renal function remain an issue of concern. The study aimed at exploring the safety and efficacy of mycophenolate mofetil (MMF) as a remission-maintaining agent in children with a diagnosis of frequent relapsing or steroid-dependent NS (FRNS/SDNS) requiring continuous medication for at least 1 year. Thirty-two children thus included received MMF (1000–1200 mg/m2/day) for 7 months along with tapering doses of oral prednisolone if it was being given from before with an attempt at tapering at 0.25 mg/kg/month ultimately stopping it altogether. Individuals were followed up for at least 5 more months after stopping MMF. Out of 32 children, 26 had SDNS and 6 had FRNS with male:female ratio being 2.2:1. The mean standard deviation (± SD) age of onset of disease was 2.72 ± 1.3 years and that entry to the study was 7.17 ± 2.2 years. Significant fall in number of relapses was observed following the introduction of MMF (110 in pre-MMF12 month period vs. 52 in post-MMF 12 months [p = 0.002]). The mean relapse rate/year/patient also decreased from 3.43 ± 1.26 to 1.62 ± 1.14 after entry in the study. Significant reduction of the cumulative dose of steroid regarding mean ± SD of mg/kg/year was also found following the introduction of MMF (190.9 ± 47.81 vs. 119.09 ± 60.09 [p = 0.001]). MMF is an efficacious agent in maintaining remission and reducing steroid requirement in children with FRNS and SDNS.

Mycophenolate mofetil in patients with refractory systemic autoimmune myopathies: case series

BackgroundCurrently, there are only few studies (mostly case reports or case series) on mycophenolate mofetil (MMF) in patients with systemic autoimmune myopathies (SAM). Therefore, the goal of the present study was to evaluate the safety and efficacy of MMF (monotherapy or coadjuvant drug) in a specific sample of patients with refractory SAM: dermatomyositis, polymyositis, anti-synthetase syndrome or clinically amyopathic dermatomyositis.MethodsA case series including 20 consecutive adult patients with refractory SAM from 2010 to 2016 was conducted. After the introduction of MMF, associated or not with other drugs, the patients were followed for 6 consecutive months.ResultsIn 17 out of 20 patients MMF was introduced without any intolerance. The clinical symptoms evaluated in these patients were muscular, cutaneous and/or pulmonary activity. During the 6-month follow-up, 11 out of 17 patients had clinical and laboratory activities response with MMF, allowing significant tapering of the prednisone median dose (15 vs. 5 mg/day, P=0.005). On the other hand, in three out of 20 patients; MMF was discontinued in less than two months, because of gastrointestinal intolerance. There were no cases of serious infection or death.ConclusionsMMF was relatively well-tolerated, safe and effective in patients with refractory SAM. Further studies are needed to confirm the data found.

Are Octogenarians With End-Stage Renal Disease Candidates for Renal Transplantation?

BackgroundElderly patients are the fastest-growing group in need of renal transplantation. This study puts focus on renal transplant recipients in their 80th year or longer at time of engraftment. Is there evidence to support an absolute upper age limit for renal transplantation?MethodsRecipients in their 80th year or longer, transplanted between 1983 and 2015, were included. Data were retrieved from the Norwegian Renal Registry in the end of October 2015. Graft and patient survivals were compared with recipients aged 70 to 79 years at transplantation.ResultsForty-seven patients older than 79 years were transplanted in the defined period. Median age 80.1 years, 81% were men. Median time on dialysis before transplantation was 18.5 months. All patients received an allograft from a deceased donor (median donor age, 61.8 years). In the death-censored graft survival model, there was no statistical difference between the groups. We found improved patient and graft survivals after introduction of mycophenolate mofetil and induction with basiliximab. Patients transplanted before 2000 had increased risk of death compared with those transplanted after 2000 (hazard ratio, 3.2; 95% confidence interval, 1.2-8.7). Median uncensored graft survival for patients transplanted after the year 2000 was 5.0 year (95% confidence interval, 2.4-7.6). Median patient survival was 5.0 years (3.1-6.9) and 5-year patient survival was 55%.ConclusionsAge by itself should not be an absolute contraindication against renal transplantation. An estimated 5-year survival rate of 55% post-engraftment for an 80-year-old patient is in our opinion more than acceptable.

Rituximab: the Lupus Journey

Since the 1950s, lupus has changed from being a life-threatening condition to being treatable in most cases thanks to the introduction of steroids, immunosuppressive drugs, dialysis and renal transplantation. However, apart from the introduction of mycophenolate mofetil, successful new drugs for lupus have been hard to find in the past two decades. In an assessment of our lupus nephritis cohort over the past 30 years (Croca et al., Rheumatology. 11; 50:1424-1430), we reported that both morbidity and mortality have changed little during this period, suggesting that we have optimized the use of corticosteroids and conventional immunosuppressive drugs. If we want to seek further improvement in outcome, new approaches will be necessary. In this review, we will focus on the use of rituximab in the treatment of systemic lupus erythematosus (SLE). Although not fully understood, it has become clear that B cells play a key role in SLE pathogenesis. They are implicated in the production of autoantibodies, presentation of autoantigen to T cells, T cell activation and cytokine production. In theory, B cell-targeted therapies which eliminate pathogenic B cells and promote the expansion and function of protective B cells, or both, should be beneficial (Rahman and Isenberg, N Engl J Med. 2008; 358:929–39), (Yildirim-Toruner and Diamond, J Allergy Clin Immunol. 2011; 127:303-12). Many open-label and registry studies do indeed report the successful use of rituximab in both renal and non-renal lupus. However, two major clinical trials using it failed to meet their end points. We review the road travelled by rituximab as a lupus treatment in the past 14 years and consider where the journey is heading. • Rituximab is a safe and effective treatment for refractory SLE patients. • Early treatment with Rituximab seems to be effective and can reduce steroid burden.

Outbreak of Pneumocystis Pneumonia in Renal and Liver Transplant Patients Caused by Genotypically Distinct Strains of Pneumocystis jirovecii

An outbreak of 29 cases of Pneumocystis jirovecii pneumonia (PCP) occurred among renal and liver transplant recipients (RTR and LTR) in the largest Danish transplantation centre between 2007 and 2010, when routine PCP prophylaxis was not used. P. jirovecii isolates from 22 transplant cases, 2 colonized RTRs, and 19 Pneumocystis control samples were genotyped by restriction fragment length polymorphism and multilocus sequence typing analysis. Contact tracing was used to investigate transmission. Potential risk factors were compared between PCP cases and matched non-PCP transplant patients. Three unique Pneumocystis genotypes were shared among 19 of the RTRs, LTRs, and a colonized RTR in three distinct clusters, two of which overlapped temporally. In contrast, Pneumocystis control samples harbored a wide range of genotypes. Evidence of possible nosocomial transmission was observed. Among several potential risk factors, only cytomegalovirus viremia was consistently associated with PCP (P=0.03; P=0.009). Mycophenolate mofetil was associated with PCP risk only in the RTR population (P=0.04). We identified three large groups infected with unique strains of Pneumocystis and provide evidence of an outbreak profile and nosocomial transmission. LTRs may be infected in PCP outbreaks simultaneously with RTRs and by the same strains, most likely by interhuman transmission. Patients are at risk several years after transplantation, but the risk is highest during the first 6 months after transplantation. Because patients at risk cannot be identified clinically and outbreaks cannot be predicted, 6 months of PCP chemoprophylaxis should be considered for all RTRs and LTRs.

Successful treatment of central nervous system PTLD with rituximab and cranial radiotherapy

Primary central nervous system (PCNS) post-transplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation and is typically an Epstein-Barr virus (EBV)-induced B-cell CD20+ lymphoma. The modalities of treatment include reduction in immunosuppression, cranial radiotherapy (CRT), intravenous and intrathecal rituximab when CD20 is expressed on B-lymphocytes and PTLD cells, and chemotherapy. We report the successful treatment of EBV-driven PCNS PTLD by reduction in immunosuppression (RI), CRT, and intravenous rituximab. Our patient was an 11-year-old boy with a living-related renal transplant for end-stage renal failure (ESRF) secondary to posterior urethral valves (PUV) and bilateral renal dysplasia (BRD) and on triple immunosuppression with prednisolone, tacrolimus, and azathioprine who had a rising EBV load, which was managed with reduction in tacrolimus dose, withdrawal of azathioprine, and introduction of mycophenolate mofetil (MMF). The patient presented 7 years post-transplant with a seizure and abnormal neurology secondary to polymorphous hyperplastic lesions in the brain, which responded to rituximab and CRT.

Calcineurin inhibitors in liver transplantation – still champions or threatened by serious competitors?

Current strategies for immunosuppression in liver transplant (LT) recipients include the design of protocols targeting a more individualized approach to reduce risk factors such as renal failure, cardiovascular complications and malignancies. Renal injury in LT recipients may be often multifactorial and is associated with increased risk of post-transplant morbidity and mortality. The quest for low toxicity immunosuppressive regimens has been challenging and resulted in CNI minimization protocols or CNI withdrawal and conversion to mycophenolate mofetil (MMF) and/or mammalian target of rapamycin inhibitor-based immunosuppressive regimens. Use of antibody induction to delay CNI administration may be an option in particular in immunocompromized, critically ill patients with high MELD scores. Protocols including MMF introduction and concomitant CNI minimization have the potential to recover renal function even in the medium and long term after LT. We review on hot topics in the prevention and management of acute and chronic renal injury in LT patients. For this purpose, we present and critically discuss results from immunosuppressive studies published in the current literature or presented at recent LT meetings.

Effects of mycophenolate mofetil introduction in liver transplant patients: results from an observational, non‐interventional, multicenter study (LOBSTER)

The benefits of calcineurin inhibitor (CNI)-sparing regimens on renal function following liver transplantation (LT) have been demonstrated in clinical studies. This observational study assessed the real-life effects of mycophenolate mofetil (MMF) introduction in LT patients. Four hundred and ninety-seven patients in whom MMF was introduced according to local standards or clinical considerations were entered. Patients were grouped by time between transplantation and start of MMF (start of study): Group A (n=263): ≤6d; Group B (n=64): >6d to ≤1month; Group C (n=74): >1month to ≤1yr; and Group D (n=96): >1yr. CNI sparing occurred in all groups, particularly in Groups C and D. Mean MMF doses at 12months were 1202.7, 1363.5, 1504.7, and 1578.1mg/d, respectively, in Groups A-D. At introduction of MMF, median glomerular filtration rate was 73.3, 81.7, 62.7, and 53.7mL/min/1.73m(2) in Groups A-D. At 12months, this decreased to 66mL/min/1.73m(2) in Groups A and B, remained stable in Group C, and increased in Group D (64.8mL/min/1.73m(2) ). Serious adverse drug reactions were lowest in Group D. In conclusion, MMF with a subsequent decrease in CNI was well tolerated and improved renal function even years after transplantation. A more forceful MMF dosing strategy with greater CNI sparing may further improve renal function.

Long-Term Impact of Hypertension on Renal Allografts

ObjectiveWe assessed the impact of hypertension on renal transplant function and survival in the past decade after introduction of mycophenolate mofetil and rituximab. MethodsWe examined the 184 patients who underwent renal transplantation from March 1982 to September 1999 and presented at our outpatient clinic from 2001 to 2011. They were divided into group 1 with mean systolic blood pressure (mSBP) >130 mm Hg and Group 2 with mSBP <130 mm Hg. We compared mean serum creatinine (sCr) levels for 9 years and 12-year actuarial graft survival rates. Risk factors for graft survival were assessed by Cox regression analysis. ResultsThere were 75 group 1 and 109 group 2 recipients. The mean sCr level of group 1 was 1.59 ± 0.12 mg/dL and that of group 2 1.54 ± 0.10 mg/dL (P < .0001). Of note was that mean sCr levels of group 1 started to increase about 3 years after transplantation. Although 5-year graft survival rates of both groups were 100%, 9- and 12-year rates among group 1 were 97.3% and 90.5%, respectively, whereas among group 2 they were 99.1% and 98.1%, respectively (P = .0195). Cox univariate and multivariate analyses showed mean SBP to be the only significant risk factor for graft survival (P < .05). ConclusionsWe concluded that the hypertensive group showed deteriorating renal function from around 3 years after transplantation that lowered graft survival afterward, resulting in a clear distinction from the nonhypertensive group at around 10 years after transplantation. Mean SBP was a significant risk factor for graft survival. Hypertension may be a surrogate for a poor renal graft prognosis in the long run.

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.

Improvement in Chronic Renal Failure after Mycophenolate Mofetil Introduction and Cyclosporine Dose Reduction: Four-Year Results From a Cohort of Heart Transplant Recipients

Chronic renal failure (CRF) due to calcineurin inhibitor (CNI) nephrotoxicity is a frequent complication among heart transplant (HT) recipients. Small studies have suggested that the introduction of mycophenolate mofetil (MMF) can help to reduce CNI doses thereby to maintaining or improving renal function. We conducted a 4-year, prospective, multicenter study in 89 maintenance HT recipients at 5.6 ± 2.7 years postgrafting who displayed CRF (serum creatinine > 1.4 mg/dL) and were undergoing treatment with cyclosporine and prednisone ± azathioprine. We introduced MMF and reduced cyclosporine to level below 100 ng/mL. Creatinine clearance (CrCl), acute rejection episodes, and survival were through retrospectively compared with a contemporary cohort of HT recipients who were not treated with MMF (control group; n = 38). After conversion to MMF, a rapid increase was observed in the CrCl, which was maintained over the follow-up: namely, CrCl at month 6 and at 4 years were 51.0 ± 15.6 and 54.1 ± 15.6 mL/min versus 41.9 ± 11.1 mL/min at baseline ( P < .0001). No renal function changes were observed among the control group. Acute rejection rates were 5.6% and 2.6% in the MMF versus control groups ( P = NS) with 4-year survivals >85%. In conclusion, the introduction of MMF allowed a safe reduction of cyclosporine and significantly improved renal function after 4 years.

Mycophenolate Mofetil Initiation in Renal Transplant Patients at Different Times Posttransplantation: The TranCept Switch Study

Despite evidence of favorable long-term effects of mycophenolate mofetil (MMF) in renal transplantation, its introduction at different times posttransplant has not been studied in large cohorts. Single-organ renal allograft recipients (n=2217) who had MMF introduced 6 months to more than 20 years posttransplantation for various reasons were included in TranCept Switch, a multicenter, noninterventional, observational 4-year study. Changes in renal function before and after the introduction of MMF were analyzed. MMF was introduced because of renal function decline in 43% of patients and poor tolerability with previous treatment in 23% of patients. The change in slope of the calculated glomerular filtration rate (modification of diet in renal diseases formula) regression line before and after MMF initiation was +2.01 mL/min per year (P<0.001) on average. The greatest benefit was noted in patients who received MMF because of renal function decline and in whom calcineurin inhibitor treatment was subsequently reduced or withdrawn (+3.09 mL/min per year). Time from transplantation to MMF introduction influenced the glomerular filtration rate at MMF initiation (slow progressive deterioration) but not the direction of the slope change, which was positive even for late introduction. MMF introduction may be associated with improvement or stabilization of renal function even several years after transplantation.

Hypogammaglobulinemia and bronchiectasis in mycophenolate mofetil‐treated renal transplant recipients: an emerging clinical phenomenon?

Mycophenolate mofetil (MMF) inhibits T- and B-cell proliferation and can cause acquired or secondary hypogammaglobulinemia. This finding and the subsequent development of opportunistic infection, including pneumonia, have been reported in patients receiving MMF. Chronic pulmonary infection and hypogammaglobulinemia predispose to bronchiectasis, and we aimed to establish the incidence and clinical pattern of this condition within our MMF-treated renal transplant population. We performed a retrospective analysis of MMF-treated transplant recipients. Two hundred and eighty-nine patients were identified and for each, demographic, clinical, radiological and laboratory data from case notes and electronic records were collected. Twenty-three of 289 patients had recurrent severe chest infections (>2 episodes) between 12 and 95 months after the introduction of MMF. The mean age was 53 ± 17yr. Pulmonary lesions fulfilled clinical, radiographic and computerized tomography criteria for bronchiectasis in 7/289 (2.4%). All seven patients with bronchiectasis had low serum IgG levels. Three patients had sufficient samples available for B-cell phenotype analysis but no conclusive results emerged. No cases of post-transplant bronchiectasis were identified in our transplant population not receiving MMF. We report seven cases of bronchiectasis in renal transplant patients receiving MMF. We speculate that low immunoglobulin levels may contribute to the development of this significant pulmonary disease.

Mycophenolate mofetil may be effective in CNS sarcoidosis but not in sarcoid myopathy

To describe effectiveness, steroid-sparing effect, and tolerance of the antiproliferative immunosuppressant mycophenolate mofetil (MMF) in neurosarcoidosis. We describe a retrospective case series of 10 consecutive patients with a diagnosis of neurosarcoidosis who were treated with MMF, alone or in association with corticosteroids, in our teaching hospital. At the time of our study, the mean duration of MMF treatment was 21 months. All but one patient with CNS involvement (n = 8) were in remission (except for hormonal dysfunction) which was complete in 6 patients. MMF was efficient as single-agent induction therapy in one patient. The 3 patients who received MMF as a maintenance therapy after initial response to corticosteroids did not relapse even though steroids were stopped. Out of 4 subjects who demonstrated insufficient response to prior therapy including corticosteroids and immunosuppressive agents, 3 demonstrated significant clinical and radiologic improvement. However, the 2 patients who presented muscular sarcoidosis did not respond to MMF. Among patients treated with steroids at MMF introduction and after excluding those with sarcoid myopathy, the mean dose of corticosteroids was 6 mg/day at the end of the follow-up while it was 59 mg/day at the initiation of MMF. No significant side effects were observed. These data suggest that MMF is effective in CNS sarcoidosis but not in sarcoid myopathy, with a corticosteroid sparing effect and a better tolerance profile than other immunosuppressive agents.

Introduction of Mycophenolate Mofetil in Maintenance Liver Transplant Recipients: What Can We Expect? Results of a 10-Year Experience

Background Mycophenolate mofetil (MMF) is a cornerstone immunosuppressive drug after liver transplantation (OLT). The aim of this study was to evaluate the long term results of the addition of MMF in maintenance OLT recipients. Methods From 1996 to 2006, MMF was introduced because of (1) histologic features of rejection or (2) calcineurin inhibitor (CNI) toxicity in order to reduce CNI dosage. Results The study population included 208 patients (median, age 54 ± 9 years), with a median delay between OLT and MMF introduction of 54 ± 43 months. The median dosage of MMF was 1180 mg/d at the end of follow-up. After a median follow-up of 50 ± 26 months, 26.4% of the patients taking MMF did present ≥1 side effect and MMF discontinuation rate was 13.8% (transient in 3.8%). The main side effects were digestive disorders (45%), pruritus ± rash ± mucitis (12.7%), and myelosuppression (16.4%). MMF was withdrawn because of digestive disorders (17.2%), pruritus ± rash ± mucitis (17.2%), and myelosuppression (24.1%). The mean glomerular filtration rate as calculated by the Cockcroft-Gault formula value significantly increased after the introduction of MMF (58.1 vs 71.4 mL/min; paired t-test; P < .01). Improvement of renal function was significantly associated with initial association with tacrolimus (vs cyclosporine), initial trough level of cyclosporine (not tacrolimus), delay between OLT and MMF introduction, and age of renal impairment. Conclusion Our results suggest that the introduction of MMF in OLT maintenance recipients is efficient and well-tolerated (one quarter of the patients presented significant side effects, leading to treatment discontinuation in 10% of the patients).

End-Stage Renal Disease After Orthotopic Heart Transplantation: A Single-Institute Experience

Orthotopic heart transplantation is the treatment of choice for end-stage heart failure, and calcineurin inhibitor agents allow for better allograft survival. However, pretransplantation low cardiac output status and posttransplantation immunosuppressants contribute toward deterioration of renal function. From 1987 to 2008, 350 patients underwent orthotopic heart transplantation in our hospital. Most of them received anti-thymocyte globulin (ATG) as the induction immunosuppressant. The introduction of mycophenolate mofetil (MMF) reduced the maintenance level of cyclosporine. The 26 patients who developed end-stage renal disease required dialysis. We reviewed the patient characteristics, including pretransplantation status, immunosuppressant regimens and drug levels, time and type of dialysis, and mortality rate. The mean age of these 26 patients was 53 years. Three patients underwent peritoneal dialysis. The overall 1-year survival rate was 96%, and the 5-year survival rate was 80%. The duration from heart transplantation to chronic dialysis correlated with the presence of a pretransplantation diagnosis of diabetes (P < .05) and an elevated pretransplantation blood creatinine level (P = .01), but there was no significant effect of the initial level of cyclosporine. In addition, the pretransplantation blood creatinine level was also related to the necessity of immediate postoperative hemodialysis (P = .01). There was no significant risk factor in relation to mortality. Regardless of modification of immunosuppressant regimens and initial drug levels, pretransplantation kidney function played an important inverse role in the duration from transplantation to dialysis: the higher the pretransplantation blood creatinine, the shorter the duration. While awaiting a heart transplant, more effort should be spent on protecting renal function to avoid early chronic dialysis.

Influence of Mycophenolate Mofetil on Preservation of Kidney Function in Liver Transplant Patients

Background There are numerous studies on the effect of immunosuppressive therapy with mycophenolate mofetil (MMF) on preservation of kidney function in liver transplant (OLT) patients with chronic kidney damage. However, we have noted few studies that evaluate the role of this drug prescribed from induction on kidney function. Patients and Methods This prospective observational multicenter study included 296 OLT performed from 2005 to 2007. The collected variables were; gender, and age, Child-Pugh stage, Model for End-Stage Liver Disease (MELD) score, transplant indication, induction immunosuppressive therapy, and baseline and 1 year posttransplant values of creatinine and glomerular filtration rate. Patients were classified into 4 groups: group 1 received MMF from induction; group 2 was never treated with MMF; group 3 started MMF in the first month posttransplant, and group 4 started MMF therapy in the third month posttransplant. We used Wilcoxon and Mann–Whitney U statistical tests. Results There was a difference of 0.18 mg/dL in baseline creatinine values between groups 1 and 2 ( P < .01). However, although patients who consistently had MMF in their treatment started with worse creatinine values, they were able to maintain them within normal ranges at 12 months. In contrast, patients in group 2 showed a significant worsening of 0.28 mg/dL in the first month that persisted throughout the study. Group 3 displayed worse baseline creatinine values than group 2 ( P < .05), and also suffered an increase of 0.29 mg/dL ( P < .01) versus baseline at 1 month. When MMF was added to their immunosuppressive therapy, the creatinine values reduced versus 1 month by 0.18 mg/dL ( P < .05). Creatinine values remained stable at the other study assessments. Group 4 showed a normal creatinine value at baseline, but were altered at 1 and 3 months ( P < .01), with increases versus baseline of 0.46 and 0.35 mg/dL, respectively. However, when MMF was introduced kidney function was restored and maintained over the study. Conclusion Early introduction of MMF improved creatinine values among patients with impaired kidney function, maintaining them at stable levels. Furthermore, patients with altered creatinine values at baseline did not worsen their kidney function if they receive MMF from induction.

Improvement of Renal Function After Conversion to Mycophenolate Mofetil Combined With Low-Level Calcineurin Inhibitor in Liver Transplant Recipients With Chronic Renal Dysfunction

Introduction Calcineurin inhibitors (CNI) are the main pathogenic factors for renal dysfunction in solid organ transplant recipients. Introduction of non-nephrotoxic immunosuppressive drugs, such as mycophenolate mofetil (MMF), may allow discontinuation or reduction of CNI treatment, thereby improving renal function. The aim of this study was to assess the feasibility, efficacy and safety of MMF introduction and CNI dosage reduction in the maintenance immunosuppressive protocol to improve renal function in liver transplant recipients with chronic renal dysfunction. Patients and Methods We prospectively included 88 liver transplant recipients including 74 men and an overall mean age of 58.8 ± 10.3 years who all displayed chronic renal dysfunction (creatinine >1.4 mg/dL) and proteinuria <1 g/d. They were subdivided into 3 groups according to the basal creatinine value 1.4–1.7 mg/dL (group I; n = 41); 1.8–2.0 mg/dL (group II; n = 28); and >2 mg/dL (group III; n = 19). MMF was initiated at 1.5–2.0 g/d. Reduction of tacrolimus or cyclosporine dosage was performed to achieve respective target trough levels of <5 ng/mL or <50 ng/mL. We performed periodic determinations of arterial pressure, liver function tests, serum creatinine, blood cells count, CNI levels, and proteinuria. Results Creatinine values after conversion were 1.4 ± 0.5 mg/dL in the overall group. Improvement of renal function was more frequent among groups I (80.4%) and II (92.8%) versus III (73.6%). Normalization of creatinine values was more frequent in group I (68.2%) with respect to cohorts II (21.4%) and III (10.5%). Rejection was not detected. Conclusion Application of an immunosuppressive protocol with MMF and low-level CNI in liver transplant recipients with chronic renal dysfunction was associated with improvement or normalization of creatinine, without an increased risk of rejection. Early conversion is needed to achieve the best results.