[Show abstract][Hide abstract] ABSTRACT: Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA.
We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months.
Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 +/- 17) than standard patients (29 +/- 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017).
We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reactions.
[Show abstract][Hide abstract] ABSTRACT: Chronic allograft nephropathy (CAN) leads to the majority of late graft loss following renal transplantation. Detection of CAN is often too late to permit early intervention and successful management. Most current strategies for managing CAN rely on minimizing or eliminating calcineurin inhibitors (CNIs) once CAN has become established. The proliferation signal inhibitors everolimus and sirolimus have potent immunosuppressive and antiproliferative actions, with the potential to alter the natural history of CAN by reducing CNI exposure whilst avoiding acute rejection. Whilst data will be forthcoming from a number of clinical trials investigating this potential, we discuss early detection of CAN and the rationale for a role for this class of agent.
No preview · Article · Aug 2009 · Clinical Transplantation
[Show abstract][Hide abstract] ABSTRACT: Hepatitis B (HBV) and hepatitis C (HCV) virus infections are major risk factors affecting long-term morbidity and mortality after renal transplantation. Hepatitis prevalence is subject to geographical variations.
To compare and analyze the geographical prevalence, risk factors and impact of HBV and HCV infection in multinational cohorts of renal transplant recipients.
From 1989 - 2002, data on 12,856 kidney transplant recipients in 37 countries were collected within the prospective MOST (Multinational Observational Study in Transplantation). Subgroup analyses of hepatitis-related prevalence, risk factors and impact were conducted on patients whose HBV and HCV status was available at time of transplantation. Countries were substratified according to population prevalence of > or = 5% HBV or > or = 10% HCV.
The prevalence of HBV was 2.9%, of HCV 8.7% and of HBV together with HCV 0.4%. Risk factors for hepatitis infection in renal transplant recipients were long dialysis time, retransplantation and blood transfusions. At each study endpoint up to 5 years after transplantation, no significant differences in graft function were observed, although the 1-year acute rejection rate tended to be lower in HCV+ patients. At 5 years post-transplant, there were no differences between the subgroups and regions regarding infections, post-transplant diabetes mellitus or malignancies including PTLD.
Overall, HCV infections are more prevalent than HBV. Despite large geographical differences in prevalence, HBV and HCV status did not appear to have a significant impact on renal graft function, infections, malignancies and post-transplant diabetes mellitus up to 5 years after renal transplantation throughout the MOST countries.
No preview · Article · May 2009 · Clinical nephrology
[Show abstract][Hide abstract] ABSTRACT: During the past decades, organ transplantation has become a frequently performed routine procedure offered to patients with
end-stage organ failure. Transplant recipients live longer, have a good quality of life, and represent therefore a rapidly
growing population. Although the follow-up, and especially the immunosuppressive therapy, are maintained by specialized transplant
centers, such patients increasingly appear in private offices or hospitals that lack particular expertise in transplant medicine.
Thus, there is need for an educational network for physicians and health care workers and for guidelines how to care best
for this cohort of patients.
No preview · Article · Feb 2009 · Cancer treatment and research
[Show abstract][Hide abstract] ABSTRACT: Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.
Full-text · Article · Apr 2008 · American Journal of Transplantation
[Show abstract][Hide abstract] ABSTRACT: While advances in immunosuppressive therapy have allowed dramatic improvements in the control of acute allograft rejection, there is still a need to improve long-term graft and patient survival rates following renal and heart transplantation. Among the recognized threats to long-term organ survival are chronic allograft dysfunction in the form of chronic allograft nephropathy and cardiac allograft vasculopathy, with long-term patient morbidity and mortality further compromised by higher than normal rates of posttransplant cardiovascular disease, infection, and malignancy. A growing body of evidence finds that the selection and dosing of immunosuppressive therapies can have great influence on long-term transplantation outcomes. Early evidence suggests that the proliferation signal inhibitors (PSIs), everolimus and sirolimus, might offer effective immunosuppressive activity together with antiproliferative effects that may address some of the unmet needs in the long-term therapeutic management of the posttransplant patient. This review summarizes the emerging evidence for employing PSI-based immunosuppression to seek a balance between the goals of maximizing graft and patient survival, while minimizing the risks of adverse events and long-term complications. Based on the proceedings of an international gathering of nephrologists, cardiologists and surgeons at the inaugural PSI Forum meeting "Proliferation signal inhibitors in transplantation: questions at the cutting edge," this paper aims to provide both an evidence base and practical guidance for transplant physicians seeking to optimize their use of PSI treatment and highlights avenues of ongoing research into the clinical potential of this class of immunosuppressive therapy.
No preview · Article · Jan 2008 · Transplantation Proceedings
[Show abstract][Hide abstract] ABSTRACT: The aim of our study was to investigate a potential influence of elevated serumcobalt and serumchromiumlevels on renal function at minimum 10 years after implantation of a metal-on-metal hip.
Between November 1992 and June 1994 98 patients (44 m, 54 f) with an average age of 56 (22-79) years received a metal-on-metal bearing Metasul. At the time of the 10-year follow-up, 15 patients had died and 8 were lost to follow-up. The remaining 75 patients had laboratory analysis including serumcreatinine and full blood cell count as well as chromium and cobalt serum levels.
Ten years postoperatively the median serumcreatinine level was 0.86 (0.55-1.51) mg/dl, the serumcreatinine clearance Ccr was in the normal range. The hemogram did not differ from that measured at the time of surgery. The median serumcobalt concentration was 0.75 (0.3-50.10) microg/l and the serumchromium concentration was 0.95 (0.3-58.6) mug/l, 10 years postoperatively.
Our long-term data do not show any influence of serum cobalt or chromium concentrations on renal function following total hip arthroplasty.
Preview · Article · Nov 2007 · Archives of Orthopaedic and Trauma Surgery
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether plasma concentrations of the acyl (AcMPAG) and phenolic (MPAG) glucuronide metabolites of mycophenolic acid (MPA) were related to diarrhoea in renal transplant patients on mycophenolate mofetil (MMF) with cyclosporine (CsA) or tacrolimus (TCL). Blood samples (0, 30, 120 min) were taken at days 3, 10, week 4, months 3, 6 and 12 for determination of MPA, MPAG and AcMPAG. MPA-AUC was estimated using validated algorithms. Two hour AUCs were calculated for MPAG and AcMPAG. Immunosuppressive therapy consisted of CsA/MMF (n= 110) and of TCL/MMF (n= 180). In 70/290 (24%) patients 86 episodes of diarrhoea were recorded during 12 months. Significantly more patients on TCL (31.1%) suffered from diarrhea compared to CsA (12.7%). MMF dose, MPA-AUC and the 2 h AUCs of MPAG and AcMPAG did not differ between patients with and without diarrhoea. Plasma AcMPAG and MPAG concentrations were substantially higher in patients on CsA compared with TCL, while MPA-AUC was lower in the former group. These data support the concept that CsA inhibits the biliary excretion of MPAG and AcMPAG, thereby potentially reducing the risk of intestinal injury through enterohepatic recycling of MPA and its metabolites.
Full-text · Article · Aug 2007 · American Journal of Transplantation
[Show abstract][Hide abstract] ABSTRACT: Registry data show that there is an overall 3-5-fold increase in cancer risk in transplant recipients compared with the general population, with skin cancers and lymphoma particularly prevalent. Cancers in transplant recipients are often more aggressive than those in the general population, with poor prognosis, particularly for gastrointestinal tumours and lymphomas. Risk factors for post-transplant malignancy include factors common to the general population, such as increasing age, cigarette smoking and sun exposure. In addition, immunosuppression is an important factor in the development of post-transplantation cancer, although data for individual agents are not definitive. A number of studies have demonstrated that ciclosporin is associated with an increased risk of malignancy, whereas a few studies report no increase in risk of cancer after the introduction of ciclosporin into treatment regimens. Similarly, studies have shown that the mycophenolic acid-based agent mycophenolate mofetil is associated with an increased risk of malignancy, whereas other studies have demonstrated that mycophenolate mofetil is in fact associated with a lower risk. Polyclonal anti-thymocyte antibodies used for induction therapy appear to be related to an increased incidence of post-transplant lymphoproliferative disorder, but this effect is not observed with monoclonal anti-interleukin 2 antibodies. Azathioprine has been implicated in the development of skin tumours, possibly as a result of increased photosensitivity to ultraviolet light. The proliferation signal inhibitors appear to be associated with a reduced risk of some malignancies. Further research will elucidate the role of these newer immunosuppressive agents in post-transplantation malignancies.
Preview · Article · Jun 2007 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: Increasing success in renal transplantation and longer patient survival has meant that post-transplant malignancies are having an increasing impact on long-term graft and patient survival. Choice of the immunosuppressive agents provides one of the controllable risk factors for the development of malignancies in this population. Calcineurin inhibitors (CNIs) are associated with an increased incidence of cancers, whereas the proliferation signal inhibitors (PSIs), everolimus and sirolimus have demonstrated anti-oncogenic effects in pre-clinical models and are currently being investigated as anti-cancer agents in clinical trials. There is increasing evidence demonstrating a lower incidence of post-transplant malignancies in renal transplant recipients receiving PSI-based immunosuppression compared with those receiving CNIs. Conversion from CNIs to PSIs has been shown to lead to the regression of Kaposi's sarcoma in renal transplant recipients and is now part of accepted standard care for this tumour in this setting. The anti-cancer properties of PSI-based regimens have the potential to combine the dual benefits of immunosuppression without the use of CNIs and the direct anti-oncogenic effects through their inhibition of the mammalian target of rapamycin (mTOR) signalling pathway. In the absence of formal clinical trial evidence on the best way to use PSIs in this setting, a workshop was held to provide practical guidance on immunosuppressive strategies in the context of malignancy, given the current state of knowledge.
Full-text · Article · Jun 2007 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: A 12-month multicenter, double-blind trial in which maintenance renal transplant patients were randomized to remain on mycophenolate mofetil (MMF) or convert to enteric-coated mycophenolate sodium (EC-MPS, myfortic) has demonstrated that conversion from MMF to EC-MPS is safe. Patients completing the study were invited to enter an open-label extension. Upon entry to the extension, patients who had received MMF during the randomized phase were converted to EC-MPS ("newly-exposed EC-MPS" group) and were monitored separately from those who had been randomized to EC-MPS ("long-term EC-MPS" group). The aim of the extension study was to collect long-term safety and efficacy data on EC-MPS, and to confirm the safety of conversion from MMF to EC-MPS in a larger patient population.
All patients received EC-MPS 720 mg b.i.d. with cyclosporine microemulsion and corticosteroids per local practice. Data derived from the analysis of the first 24 months of the extension phase are presented.
Of the 297 patients who completed the core study, 260 (88%) entered the extension; 195 (75%) completed the 24-month extension visit. For on-treatment patients > 95% of the planned daily dose of EC-MPS was administered, and < 13% of patients in both groups had discontinued EC-MPS due to adverse events by 24 months. The overall incidence of adverse events during the extension phase, including infections and hematological abnormalities, was comparable to that seen in the core study, with a similar safety profile in the newly-exposed and long-term EC-MPS groups. There were 3 deaths during the first 24 months of the extension, and 2 graft failures in both the "newly-exposed" and "long-term" EC-MPS groups.
These data demonstrate that long-term use of EC-MPS is effective and has an acceptable tolerability profile in renal transplant patients, and confirm that conversion of maintenance renal transplant patients from MMF to EC-MPS is a safe therapeutic option.
No preview · Article · Sep 2006 · Clinical nephrology
[Show abstract][Hide abstract] ABSTRACT: Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary nonfunction and delayed graft function (DGF) than heart beating cadaveric donor (CAD) kidneys, but little is known about long-term function of DCD grafts that survive to 1 year. To investigate the outcomes of renal transplant recipients whose DCD graft functioned for at least 1 year, this study analyzed data collected from 326 DCD graft recipients and 340 CAD-matched controls enrolled in a prospective, multinational, observational study--Neoral-MOST (Multinational Observational Study in Transplantation) (Novartis, Basel, Switzerland). No differences were found in the demographics or immunosuppression between the two groups. All patients received a Neoral-based immunosuppressive regimen. Donors after cardiac death graft recipients had a higher incidence of DGF (40% vs. 27% CAD; P < 0.001). One year glomerular filtration rate (GFR) and GFR-decline after 1 year were similar in DCD and CAD recipients (GFR 56 ml/min DCD vs. 59 ml/min CAD; GFR-decline -1.3 ml/min DCD vs. -1.4 ml/min CAD; P = not significant). Multifactorial analyses confirmed that GFR at 1 year was significantly influenced by donor age and gender, DGF, and acute rejection; however, DCD status was not an independent risk factor in cyclosporine-treated patients with grafts that had functioned for at least 1 year.
Full-text · Article · Sep 2006 · Transplant International
[Show abstract][Hide abstract] ABSTRACT: Calcineurin inhibitors (CNIs) are associated with important side effects, such as nephrotoxicity, and thus there is an interest in developing CNI-sparing protocols using agents such as the proliferation signal inhibitor/mammalian target of rapamycin inhibitor everolimus. In a 3-month pilot study using an abrupt conversion protocol, ciclosporin (CsA) treatment was stopped after the morning dose and everolimus was started at 3.0 mg/day. Mycophenolic acid (MPA)-based therapy was continued, or prednisolone increased to 10 mg/day until target everolimus trough blood levels (3-8 ng/ml) were achieved. To date, seven patients have been enrolled, with three having completed at least 3 months of follow-up. Overall, conversion was effective and well-tolerated. Patients consistently achieved everolimus trough blood levels >3 ng/ml, and no episodes of acute rejection or proteinuria were reported after 3 months. In patients who completed the study, there were no major changes in the leucocyte or platelet counts during everolimus treatment. Serum creatinine levels were maintained or decreased slightly. One patient experienced a transient increase in serum creatinine during an episode of pneumonia, but levels decreased again after resolution of infection and temporary everolimus dose reduction. Serum cholesterol and triglyceride levels increased, but remained within acceptable limits. One patient receiving enteric-coated mycophenolate sodium 1440 mg/day experienced increasing everolimus trough blood levels and anaemia after conversion, and was therefore likely to have been over-immunosuppressed. Abrupt conversion to everolimus from CsA was effective and well-tolerated in renal transplant recipients. A reduction in MPA dosage at the time of conversion may be necessary to prevent over-immunosuppression.
Preview · Article · Aug 2006 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: In earlier registry analyses, cyclosporine at doses of < 3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST.
Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age > 60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (<65 mL/min) included donor or recipient age >60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose <3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point.
Compared to higher doses, CsA-ME <3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.
Full-text · Article · May 2006 · Transplantation Proceedings
[Show abstract][Hide abstract] ABSTRACT: Long-term success of renal transplantation depends upon the quality of the donor organ, avoidance of peritransplant and early posttransplant damage (rejection), and optimal maintenance of graft function after the first 6-12 months. Glomerular filtration rate (GFR) at 1 year is a standard way to evaluate short-term success, whereas calculated GFR at 5 years gives a better appreciation of long-term outcomes. The objective of this study was to assess the effect of various demographic and transplant-related parameters on renal function via GFR at 1 year and 5 years post transplantation, using univariate and multivariate data analysis.
Data on 1-year GFR were available from 10,397 patients, whereas 2,889 patients provided data on both 1-year and 5-year GFR. All patients were enrolled in the Neoral Multinational Observational Study in Transplantation (Neoral-MOST), an ongoing, prospective, observational study of adult renal transplant recipients.
One-year GFR was the most relevant predictor for 5-year GFR. In a multifactorial analysis (ANCOVA) using 1-year GFR as a continuous variable, the effects of several highly relevant parameters from univariate analysis (such as acute rejection and delayed graft function) on 5-year GFR appeared to be fully mediated by their influence on 1-year GFR, whereas immunological risk factors like HLA match or previous transplantation had an ongoing effect on graft function beyond year 1.
The findings of this study corroborate and augment data from previous registry surveys, and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome.
[Show abstract][Hide abstract] ABSTRACT: The hyperlipidemic and hypertensive effects of ciclosporin constitute a cardiovascular risk. Cosmetic side-effects are known to reduce patients' quality of life. This was a 6-month, open, prospective, multicentre study in 296 adult kidney transplant patients to evaluate the conversion from ciclosporin to a tacrolimus-based regimen. Primary indications for conversion were hyperlipidemia (n =77), hypertension (n = 72), hypertrichosis (n = 32) and gingival hyperplasia (n = 115). At month 6, hyperlipidemia and hypertension were at least moderately improved in 59.1% and 63.5% of patients, and strongly or completely resolved in 29% and 25%. Gingival hyperplasia and hypertrichosis were strongly or completely resolved in 73% and 72% of patients. Mean total cholesterol was reduced from 255 to 218 mg/dl. Mean systolic blood pressure (SBP) was reduced from 152.9 to 137.5 mmHg and mean diastolic blood pressure (DBP) from 90.7 to 85.8 mmHg. Ciclosporin-related side-effects resolved or improved after conversion to tacrolimus.
Preview · Article · Aug 2005 · Transplant International
[Show abstract][Hide abstract] ABSTRACT: Mycophenolate mofetil (MMF) has greatly reduced the risk of acute rejection episodes (ARE) after renal transplantation, but dose reductions/withdrawals could jeopardize long-term results.
The MOST database of "de novo" patients treated with MMF at month 1 and functioning grafts at month 12 were divided into 2 groups: groups 1, 2 g MMF at month 1 and month 12; and group 2, 2 g MMF at month 1 but MMF <2 g at month 12 to evaluate renal function glonerular filtration rate (GFR).
In this study, 1136 patients were receiving 2 g MMF at month 1. On month 12, 645 were on 2 g (56.8%, group 1) and 431 were on <2 g (43.2%, group 2). Group 1 included younger recipients of younger donors with fewer patients with delayed graft function (DGF). Group 1 showed more ARE during month 1 and more patients who received induction. Mean Neoral daily doses at month 1/month 12 were 5.3/3.0 and 5.3/3.1 mg/kg in group 1 and group 2, respectively (P = .05 at month 12). GFR in group 1 and group 2 were 59.06 (CI 57.10-60.60) and 53.81 (CI 52-55.7) at month 1 (P < .001); 63.7 (CI 62.1-65.30) and 55.9 (CI 54.1-57.7) mL/min*1.73 m(2) at month 12 (P < .001). The mean increases in GFR between month 1 and month 12 were 4.64 and 1.94 mL/min*1.73 m(2), respectively (P < .05). A multivariate analysis also included 795 patients from the "maintenance" patient database with retrospective detailed information. The following parameters were highly predictive for good renal function at month 12: donor age younger than 60 years, recipient age younger than 60 years, immediate graft function, 12-month MMF dose = 2 g, absence of CMV infection, and 12-month Neoral dose <3 mg/kg/d.
Maintenance of MMF dose at 2 g/d during the first year appears to facilitate the attainment of optimal renal function at 12-months after kidney transplantation.
No preview · Article · Jul 2005 · Transplantation Proceedings
[Show abstract][Hide abstract] ABSTRACT: In an open, prospective, multicenter study, stable renal graft recipients were converted to tacrolimus because of cyclosporine-related side effects. Seventy-five patients were switched primarily because of hyperlipidemia. After the switch to tacrolimus, mean total cholesterol was reduced by 15% at month 6. One hundred seventy-seven additional patients were switched primarily for other indications: hypertrichosis, gingival hyperplasia, and arterial hypertension, and these symptoms also improved after the switch. In this analysis, serum lipid levels were categorized according to a modified standard classification of lipid parameters for renal transplant patients (published by the NKF Work Group). The aim was to estimate the proportion of patients reaching normal lipid levels after the conversion to tacrolimus therapy. In patients with primary indication hyperlipidemia, the proportion with normal cholesterol levels increased significantly from 5.6% at baseline to 37.5% at month 6 (P < .05). For LDL cholesterol, the increase was from 54.1% at baseline to 64.9% at month 6, and for triglycerides the improvement was from 25.4% to 33.8%. HDL cholesterol levels remained stable. Similar changes of lipid parameters were also observed in the subgroups of patients converted to tacrolimus primarily because of other indications. After conversion from cyclosporine to tacrolimus, a significantly higher proportion of stable renal graft recipients reached normal total cholesterol levels. For LDL cholesterol and triglycerides, a trend for normalization was observed. Thus, the improvement of serum lipid levels resulted for many patients in a change to a better level class and improved or normalized their cardiovascular risk parameters.
No preview · Article · Jun 2005 · Transplantation Proceedings
[Show abstract][Hide abstract] ABSTRACT: Enteric-coated mycophenolate sodium (EC-MPS) is an enteric-coated formulation of mycophenolic acid. A 12-month, multicenter, double-blind, randomized clinical study demonstrated that converting maintenance renal transplant patients from mycophenolate mofetil (MMF) to EC-MPS is safe and does not affect efficacy. In an open-label study extension, 130 patients initially randomized to MMF were converted to EC-MPS (newly exposed); 130 initially randomized to EC-MPS continued on EC-MPS (EC-MPS long-term). A composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, or death occurred in 3 (2.3%) newly exposed and 2 (1.5%) EC-MPS long-term patients during the extension phase. One patient died and one lost his graft. BPAR occurred in 3 (2.3%) newly exposed patients and 1 (0.8%) EC-MPS long-term patient. During the first 12 months of the extension phase, incidence and type of adverse events was similar in both groups and comparable to that seen in the core study. Nine cases of malignancy were reported, mainly nonmelanoma skin cancers. EC-MPS dose adjustments for adverse events were required in <12% of patients. At the end of the 12-month extension, 58 (44.6%) and 64 (49.2%) newly exposed and EC-MPS long-term patients, respectively, had reported at least one gastrointestinal adverse event. Mean serum creatinine remained stable at the 12-month visit of the extension study (137 micromol/L in the newly exposed and 142 micromol/L in the EC-MPS long-term groups). The results of this study demonstrate the long-term safety of EC-MPS and reconfirm the safety of converting MMF maintenance renal transplant patients to EC-MPS.
No preview · Article · Mar 2005 · Transplantation Proceedings