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.     

Combination therapy with tacrolimus and mycophenolate mofetil: effects of early and late minimization of mycophenolate mofetil after renal transplant

The objectives of the study were: (i) to compare the efficacy and safety of minimizing mycophenolate mofetil (MMF) early (30 d) or late (90 d) after renal transplantation, when used in combination with tacrolimus; (ii) to retrospectively investigate factors associated with early, acute rejections and (iii) to investigate the pharmacokinetic interaction between tacrolimus and diltiazem. A prospective, randomized, multicenter, open-label study was conducted in 124 de novo kidney transplant recipients. Efficacy and safety outcomes were assessed for 180 d after transplantation and subjects were followed-up for a mean duration of 5.1 yr. The efficacy and safety outcomes were comparable whether the dose of MMF was minimized early or late. The incidence of early, acute rejection episodes was higher for recipients who were younger, received a graft from an unrelated donor or failed to achieve adequate tacrolimus concentrations (trough > 10 ng/mL) in the first seven d after transplant. Concomitant use of diltiazem had a tacrolimus-sparing effect in some subjects. Based on these results, we support the achievement of a high target tacrolimus concentration within the first week after renal transplant and suggest that early minimization of MMF can be achieved when used in combination with tacrolimus.     

Five-year results of renal transplantation on immunosuppressive triple therapy with mycophenolate mofetil

Mycophenolate mofetil (MMF) combined with cyclosporine and prednisolone significantly lowers acute rejection frequency in the early post-renal transplantation phase. To date only registry data with very high transplant numbers have shown that MMF significantly influences long-term outcome. A comparative retrospective analysis of the 5-yr results with MMF in a single transplant center was thus undertaken vs. other standard immunosuppressive regimens. The results of 1579 renal transplantations were grouped by treatment modality, subjected to Kaplan-Meier analysis, and compared using the log rank test. Both the total population and subgroups showed a non-significant trend towards better graft survival with MMF, evident at 2 yr and persisting for 5 yr. Extrapolation indicates that on combination therapy with MMF vs. azathioprine, approximately 10% more patients will be alive at 10 yr with a functional graft.     

Discontinuation of mycophenolate mofetil from a tacrolimus-based triple regimen 2 months after renal transplantation: a comparative randomized multicentre study

Previous clinical data suggested that with a tacrolimus-based regimen adjunctive immunosuppressives may be withdrawn after an initial treatment period. This study investigated the early discontinuation of mycophenolate mofetil (MMF) from a standard triple regimen. Patients were randomized either to receive a continued tacrolimus/MMF/steroids triple regimen (control group) or to reduce and then stop the MMF dose (MMF stop group). Both groups received identical daily tacrolimus and corticosteroid doses. The initial MMF dose was 1 g/day in both arms, but in the MMF stop group the dose was reduced to 0.5 g/day from week 7 to week 12 and then stopped. The intent-to-treat population consisted of 74 (control) and 78 (MMF stop) patients. MMF was tapered off as planned in 82.9% of the patients in the MMF stop arm. The 6-month incidence of biopsy-proven acute rejection was similar in both arms (21.6% control, 16.7% MMF stop). Graft loss occurred in 5.4% (control) and 3.8% (MMF stop) of the patients. MMF could be safely discontinued from a tacrolimus-based triple therapy early after transplantation without any rebound in efficacy during the 6-month follow-up period. (Name of registry: ClinicalStudyResults.org, number: FG-02-CEE-01, date: 9 June 2006).     

Increased incidence of allograft rejection in stable heart transplant recipients after late conversion from mycophenolate mofetil to azathioprine.

Mycophenolate mofetil (MMF) is a safe and effective immunosuppressive agent in kidney and liver transplantation. Preliminary studies also support its use in heart transplantation. However, the cost of MMF is substantially greater than azathioprine (AZA), the current alternative. Since the majority of rejection episodes occur within the first few months of transplantation, using MMF early after transplantation and subsequently converting to AZA, after the risk of rejection has diminished, might be cost-effective. In order to evaluate the safety of such a strategy in heart transplant recipients, we reviewed the rejection profiles of a group of patients who were converted from MMF to AZA late after transplantation. Forty-three stable patients on chronic MMF therapy as part of an open-label, long-term safety study were converted to either commercially available MMF (CellCept) or AZA, at the conclusion of the study. Demographic variables, rejection histories before and after conversion, and immunosuppressive regimens were examined. Twenty-three patients were continued on commercial MMF and 20 were converted to AZA therapy. The average duration of MMF therapy prior to conversion was 41 months in each group. Baseline demographics were similar in the two groups. Treated allograft rejection occurred in 10 of 20 patients converting to AZA, as compared to only 1 of 23 patients remaining on MMF; p = 0.002. Additionally, mean scores (1-5 scale) for the three biopsies before and after conversion favored continued MMF therapy (1.5+/-0.6 before and 1.2+/-0.4 after conversion in MMF group vs. 1.3+/-0.5 before and 1.7+/-0.9 after conversion to AZA; p = 0.02). No allograft loss occurred as a result of conversion. These data suggest that conversion from MMF to AZA, even late after transplantation, can be associated with allograft rejection. The costs associated with these rejection episodes (the additional immunosuppressive agents, endomyocardial biopsies, and physician visits) may exceed the potential cost savings of converting stable heart transplant recipients from MMF to AZA.     

Four-year follow-up of a prospective randomized trial of mycophenolate mofetil with cyclosporine microemulsion or tacrolimus following liver transplantation

BACKGROUND: This is a 4-yr follow-up of a trial using mycophenolate mofetil (MMF) induction in orthotopic liver transplantation (OLT). The goal of this study was to evaluate a multidrug approach that would reduce both early and long-term morbidity related to immunosuppression while maintaining an acceptable freedom from rejection. METHODS: This was a prospective, randomized, intent to treat study designed to compare the primary endpoints of rejection and infection, and secondary endpoints of liver function, renal function, bone marrow function, cardiovascular risk factors, and the recurrence of hepatitis C. Ninety-nine consecutive patients with end stage liver disease who underwent OLT were randomized to receive either cyclosporine microemulsion (N) (50 patients) or tacrolimus (FK) (49 patients) starting on postoperative day 2, with MMF and an identical steroid taper begun preoperatively. RESULTS: Ninety of 99 patients (N 46, FK 44) completed the 4-yr follow-up. The overall 4-yr patient and graft survivals were 93 and 89%, respectively. There was no significant difference in 4-yr patient (N 96% vs. FK 90%, p = ns) or graft (N, 90% vs. FK, 88%, p = ns) survival between groups. The 4-yr rejection rate was not significantly different in either arm (N = 34%, FK = 24%; p = 0.28). There were no differences in infection rates in either arm. The patients with hepatitis C had no differences in the viral titers or Knodell biopsy scores between groups. However, in the hepatitis C subgroup (37 patients), the FK patients had a significantly lower rejection rate (p = 0.0097) and a significantly lower clinically recurrent hepatitis C rate (p = 0.05) than the N patients. No difference was seen in the percent of patients weaned off of steroids after 4 yr (N 51%, FK 49%). There were no differences in the incidences of diabetes mellitus and hypertension. When renal dysfunction was analyzed, a significant difference in the number of patients whose creatinine had increased twofold since transplant was seen (N 63%, FK 38%, p = 0.04). CONCLUSIONS: Use of MMF induction and maintenance following OLT in conjunction with either N or FK and an identical steroid taper, resulted in an acceptable long-term incidence of rejection and infection, without an increase in long-term graft or patient morbidity.     

The long-term effect of switching from cyclosporin A to mycophenolate mofetil in chronic renal graft dysfunction compared with conventional management.

BACKGROUND: To overcome toxicity of calcineurin inhibitors, recent trials have proposed substituting cyclosporin (CysA) with mycophenolate mofetil (MMF). No data concerning the long-term side effects and long-term renal outcome of this strategy have been published. METHODS: We retrospectively compared 39 renal transplant patients with chronic graft dysfunction who were subjected to CysA to MMF substitution (group 1) with 39 matched renal transplant patients who were continued on conventional management (group 2). The mean serum creatinine and the slope of deterioration of renal function before the date of the therapeutic intervention (T(0)) were similar in both groups. Follow-up in both groups was 76 +/- 42 months before T(0) and 44 +/- 11 months after T(0). RESULTS: In group 1, conversion was associated with a decrease of mean serum creatinine concentrations from 192 to 172 micro mol/l at 1 year (P = 0.004) and 159 micro mol/l at 3 years (P < 0.003) after T(0), whereas it remained unchanged in group 2. The systolic blood pressure decreased in group 1 from 155 mmHg before T(0) to 145 mmHg at 1 year (P < 0.01) and 133 mmHg at 3 years (P < 0.001) without any increase of the antihypertensive drug, whereas it did not change in group 2. Lipid profile tended to improve in group 1 after T(0) and was unchanged in group 2. None of the patients in group 1 developed acute rejection after T(0), whereas two acute rejections occurred in group 2. Graft survival, however, was similar in both groups. In group 1, several side effects occurred related to MMF treatment, and led to its discontinuation in two cases and the reduction of its dose for 18 patients (64%). CONCLUSION: CysA/MMF substitution improves renal function and blood pressure in chronic allograft dysfunction when compared with conventional management. However, CysA/MMF substitution is associated with a high rate of MMF-related side effects, requiring modulation of its dose.     

Efficacy and safety of 'rescue therapy' with mycophenolate mofetil in resistant primary glomerulonephritis--a multicenter study.

BACKGROUND: Studies of mycophenolate mofetil (MMF) in primary glomerulonephritis have varied in their inclusion criteria, regimen and follow-up compromising assessments of efficacy and optimal dose. METHOD: This multicentre study analysed the safety and efficacy of MMF monotherapy in a large cohort with primary glomerulonephritis that was resistant to other conventional therapies. A total of 98 patients with biopsy-proven primary glomerulonephritis resistant to other drugs received MMF monotherapy for 1 year. Primary outcome measures were urinary protein excretion and the number of patients with complete or partial remission of proteinuria. Secondary analyses were time to remission and changes in the slope of creatinine clearance. RESULTS: Fifty-four percent of the patients achieved either complete or partial remission of proteinuria with no significant differences between glomerulonephritis types. Median (range) dose of MMF was 2 g/day (1.5-2 g/day) Mean (SD) treatment time to remission was 141.5 (+/-61.1) days with no significant differences between glomerulonephritis types. Serum albumin increased (P<0.01), whereas proteinuria (P<0.01) serum LDL-cholesterol (P<0.01) and mean blood pressure (P<0.05) decreased post-treatment. No significant changes were observed in glomerular filtration rate (GFR), serum creatinine or slopes of GFR. The reduction of urinary protein excretion was significantly higher in patients with basal nephrotic proteinuria and preserved renal function; it did not arise from an increased dose of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, since, among responders, mean blood pressure significantly decreased and the number of anti-hypertensive drugs could be reduced. CONCLUSIONS: MMF monotherapy causes a moderate decrease in proteinuria in >50% of the patients who do not have other treatment options. The response to therapy is largely influenced by a preserved renal function and requires sustained MMF treatment.     

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): ≤6 d; Group B (n = 64): >6 d to ≤1 month; Group C (n = 74): >1 month to ≤1 yr; and Group D (n = 96): >1 yr. CNI sparing occurred in all groups, particularly in Groups C and D. Mean MMF doses at 12 months were 1202.7, 1363.5, 1504.7, and 1578.1 mg/d, respectively, in Groups A–D. At introduction of MMF, median glomerular filtration rate was 73.3, 81.7, 62.7, and 53.7 mL/min/1.73 m² in Groups A–D. At 12 months, this decreased to 66 mL/min/1.73 m² in Groups A and B, remained stable in Group C, and increased in Group D (64.8 mL/min/1.73 m²). 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.     

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

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

Treatment of idiopathic membranous nephropathy with the combination of steroids, tacrolimus and mycophenolate mofetil: results of a pilot study.

BACKGROUND: Membranous nephropathy is a common cause of nephrotic syndrome (NS) in adults. Its treatment is still under debate. METHODS: We report our experience in a pilot study using initially low doses of steroids and tacrolimus (Tac). After 3 months of treatment, mycophenolate mofetil (MMF) was added if the proteinuria was higher than 1 g/day. RESULTS: In accordance with this standard, 21 patients entered the study. A proteinuria level lower than 1 g/day was reached at month 3 of therapy with steroids and Tac in 11 patients. These patients continued this treatment for 12 months. MMF was added in nine cases after the third month and triple therapy was maintained for 12 more months. Two patients were withdrawn because of side effects. At the end of the treatment, remission of the NS was present in 15 out of all the patients (71.4%). Remission of the NS was complete in eight (53.3%) patients and partial in seven (46.7%) others. The remaining four patients did not respond. There were no significant changes in renal function. At a mean time of 23.1 months after treatment was discontinued, 11 (73.3%) patients had relapsed. CONCLUSIONS: In this trial, treatment with tacrolimus showed a good efficacy but a high relapse rate when it was discontinued.     

Impact of dose reductions on efficacy outcome in heart transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil at 12 months post-transplantation

Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.     

Tacrolimus combined with mycophenolate mofetil can effectively reverse C4d-positive steroid-resistant acute rejection in Chinese renal allograft recipients.

BACKGROUND: Tacrolimus (TAC) combined with mycophenolate mofetil (MMF) has been suggested to play a critical role in the reversal of C4d-positive acute humoral rejection (AHR) in renal transplantation, but the efficacy of using only TAC-MMF without immunoadsorption or plasmapheresis has not been investigated. On the other hand, Chinese recipients of renal grafts usually need lower doses of immunosuppressants, and their optimal treatment for acute humoral rejection has not been established. METHODS: Since 1999, we have used TAC-MMF to treat steroid-resistant acute rejection (AR). C4d staining was retrospectively performed in 32 patients with steroid-resistant AR, and the treatments of 19 patients with C4d-positive steroid-resistant AR were investigated. RESULTS: Thirteen of 19 patients received TAC-MMF treatment only; 11 episodes of rejection in them were reversed (7 completely, 4 partially) and only 2 recipients lost their graft. Another 6 patients received immunoadsorption also. One of them failed to respond and lost her graft. Four of 5 patients treated with immunoadsorption and TAC-MMF recovered (3 completely, 1 partially), but 3 of them had severe pneumonia, a complication rate statistically higher than in patients treated with only TAC-MMF (P<0.05). AR occurring during the first two weeks after transplantation had a statistically better outcome than that occurring later (P = 0.003). CONCLUSION: Our study suggests that the combination of TAC and MMF is a potentially safe and economic treatment for most Chinese renal allograft recipients with C4d-positive steroid-resistant AR, especially for rejections developing within the first two weeks after transplantation.     

The use of daclizumab as induction therapy in combination with tacrolimus and mycophenolate mofetil in recipients with previous transplants

Clinical trials using daclizumab as induction therapy in combination with tacrolimus (TAC) and mycophenolate mofetil (MMF) have been shown to reduce the incidence of acute rejection episodes in solid organ transplantation. In an attempt to obtain a low rejection rate we proceeded with the use of daclizumab as induction therapy, in combination with TAC and MMF for recipients with previous transplants. In this study, we analyzed patients who received previous transplants, treated with the above immunosuppressive regimen. Group A consisted of four patients with previous liver transplants, group B consisted of 16 recipients with previous kidney transplants and group C consisted of three patients with previous simultaneous pancreas-kidney transplants. All patients underwent cadaveric kidney transplants except one patient in group B, who underwent a pancreas transplant. At 12 months, patient and graft survival for all groups was 100 and 100%, respectively. Acute rejection rate was 0% for group A, 12.5% for group B, and 0% for group C. Daclizumab induction therapy is effective for patients with previous transplants and does not appear to increase the risk of acute rejection.     

Prospective controlled study on mycophenolate mofetil and prednisolone in the treatment of membranous nephropathy with nephrotic syndrome

BACKGROUND: Retrospective and anecdotal data suggest that mycophenolate mofetil (MMF) might be effective when given as rescue therapy for membranous nephropathy (MN). Prospective controlled data on MMF and prednisolone as primary therapy are lacking. METHODS: A prospective, randomized, controlled, open-label study was performed to investigate the efficacy and tolerability of MMF and prednisolone as primary treatment in MN with nephrotic syndrome. MMF and prednisolone given for 6 months was compared against a modified Ponticelli regimen in 20 patients, with follow up of 15 months. RESULTS: MMF with prednisolone and the comparative immunosuppressive regimen showed similar efficacy in proteinuria reduction, despite a lower cumulative prednisolone dose in the MMF group (3.80 +/- 0.28 vs 9.93 +/- 0.25 g, P < 0.001). Remission (composite of 'complete' and 'partial') rates were 63.6% and 66.7% in the MMF group and control group, respectively (P = 1.000). Serum creatinine and creatinine clearance remained stable during follow up. Cumulative relapse rate was 23.1% at 2 years. Chlorambucil resulted in more leucopenia compared with MMF. CONCLUSION: Data from this pilot study indicate that more than 60% of patients with MN and nephrotic syndrome respond to combined MMF and prednisolone treatment, and suggest potential benefits of MMF as being steroid-sparing and having less adverse effects compared with other commonly used cytotoxic agents.     

Impact of mycophenolate mofetil (MMF)-related gastrointestinal complications and MMF dose alterations on transplant outcomes and healthcare costs in renal transplant recipients

Mycophenolate mofetil (MMF), a mycophenolic acid prodrug, is a highly effective adjunct immunosuppressive agent in transplant therapy. Although MMF is generally well tolerated, optimal therapy may be limited by adverse effects, in particular gastrointestinal (GI) toxicity, which has been reported to occur in up to 45% of MMF-treated patients. MMF dose changes resulting from these adverse events may lead to sub-therapeutic dosing and impaired clinical outcomes. This retrospective study analyzed clinical records from 772 renal transplant patients from 10 US transplant centers who were initiated on MMF. The analysis revealed that 49.7% (n = 382) of patients experienced at least one GI complication within the first 6 months post-transplant, with 66.8% (n = 255) of these having multiple GI complications. Of the patients with GI complications, 39.0% experienced MMF dose adjustments or discontinuation of MMF therapy. Patients with GI complications who experienced MMF dose adjustments/discontinuation had a significantly increased incidence of acute rejections compared with patients without GI complications (30.2% vs. 19.4%; p = 0.005). Mean treatment costs were higher in patients with GI complications than in those with no GI complications, particularly in those who experienced MMF dose adjustments/discontinuation (p = 0.0001). The mean incremental cost for patients experiencing GI complications was US$3700 per patient during the 6 months post-transplant (p < 0.001), which was mainly attributable to hospitalization costs. In summary, GI complications and MMF dose adjustments/discontinuations are associated with a significant negative impact on transplant outcomes and markedly increase short-term treatment costs.     

Adjunctive intracameral application of corticosteroids in patients with endothelial immune reactions after penetrating keratoplasty: a pilot study

This study was performed to gain first experiences with a new adjunctive measure in the treatment of endothelial immune reactions after penetrating keratoplasty, i.e., intracameral injections of corticosteroids. In eight penetrating keratoplasty patients with mild endothelial immune reactions (IM1), 10 patients with moderate endothelial immune reactions (IM2) and 10 patients with severe endothelial immune reactions (IM3) intracameral injections of corticosteroids were performed within 24 h after referral to the clinic, following informed consent. All patients (IM1-3) received basic therapy of steroid eye drops and subconjunctival steroid injections; patients in group IM3 also received oral steroids. In IM1 patients eight of eight grafts, in IM2 eight of 10 grafts and in IM3 five of 10 grafts remained clear during a mean follow-up of 9.9 (1-20), 10.7 (3-17) and 9.6 (1-20) months after intraocular intervention. Only one of the 28 patients developed a further immune reaction during follow-up. No complications of intracameral injection were observed. Intracameral steroid injections thus seem to be a safe and helpful therapeutic measure in the treatment of moderate and severe endothelial immune reactions after penetrating keratoplasty. Further investigations in controlled randomized trials are necessary.     

Questionnaire-based evaluation of gastrointestinal disorders in de novo renal-transplant patients receiving either mycophenolate mofetil or enteric-coated mycophenolate sodium.

BACKGROUND: Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of our prospective questionnaire-based study was to assess GI side-effects in de novo renal-transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). METHODS: Between January 2002 and April 2003, all patients receiving MPA with a functioning allograft at 1 month post-transplantation were enrolled in this study (n = 130). Ninety-three of them received MMF (group I), and 37 patients received EC-MPS (group II). Each month, every patient completed a questionnaire regarding GI disorders. RESULTS: During the first year post-transplantation, GI disorders occurred in 31 patients from the MMF group (33.3%) and 12 patients from the EC-MPS group (32.4%) (not significant). The incidence of upper GI disorders was also similar in both groups. Diarrhoea was observed in 18 patients (19.3%) from group I, and in five patients from group II (13.5%) (not significant). Its frequency and severity were similar in both groups. Weight loss was observed in three patients receiving MMF. Diarrhoea resolved spontaneously in 10 patients from group I and in all patients from group II. For the other eight patients in group I, the diarrhoea required MMF discontinuation in three patients and dose reduction in five patients. CONCLUSIONS: In conclusion, in this questionnaire-based evaluation, the incidence of GI disorders was similar in patients receiving either MMF or EC-MPS during the first year post-transplantation.