Enteric-coated mycophenolate sodium: safe conversion from mycophenolate mofetil in maintenance renal transplant recipients.

Mycophenolate mofetil (MMF), in combination with cyclosporine and corticosteroids, improves long-term graft function and survival in renal transplant recipients. However, optimal MMF therapy may be limited by gastrointestinal (GI) intolerance, which may result in the need for MMF dose reduction, interruption, or discontinuation, leading to increased risk of acute rejection. Enteric-coated mycophenolate sodium (EC-MPS) is an advanced formulation delivering mycophenolic acid (MPA), developed with the objective of improving MPA-related upper GI adverse events. A pivotal, 12-month, phase III, randomized, multicenter, double-blind, double-dummy, parallel group study investigated whether stable renal transplant patients can be converted from MMF to EC-MPS therapy without compromising tolerability or efficacy. Stable renal transplant recipients received either MMF, 1000 mg b.i.d. (n=159), or EC-MPS, 720 mg b.i.d. (n=163), for 12 months. The incidence of GI adverse events was comparable between both treatment groups at 3 and 6 months, but there was a trend toward reduced severity of GI side effects in the EC-MPS group. There were fewer serious adverse events with EC-MPS and significantly fewer serious infections (P<.05). This comparable safety profile for EC-MPS and MMF also extended to elderly patients and patients with diabetes at baseline. For the composite efficacy variable of biopsy-proven acute rejection, graft loss, death, or loss to follow-up, EC-MPS had a lower 12-month efficacy failure rate (EC-MPS: 7.5% vs MMF: 12.3%; P=ns). These data demonstrate that stable renal transplant recipients receiving MMF can be converted to EC-MPS with no efficacy or tolerability compromise.

Super high flux hemodialysis at high dialysate flows: an ex vivo assessment.

BACKGROUND AND OBJECTIVES: The removal of cytokines by standard hemofiltration is limited. Super high flux membranes may significantly improve removal even when used in dialysis mode. We sought to measure cytokine clearance using a large surface super high-flux membrane and a standard hemodialysis setting. SETTING: ICU laboratory of a tertiary institution. SUBJECTS: Six healthy volunteers. METHODS: Blood form healthy volunteers was incubated for 4 hours with E. coli endotoxin to stimulate cytokine production. Cytokine containing blood was then circulated through a dialysis circuit at 3 different dialysate flow rates. Blood and dialysate were sampled for cytokine and albumin measurements and calculation of clearances. RESULTS: Super high-flux dialysis achieved high median cytokine clearances (IL-1 clearance of 106 ml/min, IL-6 clearance of 66.8 ml/min, IL-8 clearance of 61.7 ml/min and TNF clearance of 36.1 ml/min). Increasing dialysate flow rate from 300 to 500 ml/min did not significantly increase cytokine clearances. Albumin clearances however were between 2.7 and 5.4 ml/min. CONCLUSIONS: Cytokine dialysis is feasible at high dialysate flow rates yielding high cytokine clearances. Albumin loss, however, is appreciable and may require separate supplementation in the clinical setting.

Effects of fluvastatin on cardiac events in renal transplant patients: ALERT (Assessment of Lescol in Renal Transplantation) study design and baseline data.

BACKGROUND: Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ('statins') reduces morbidity and mortality from coronary heart disease in diverse patient populations. STUDY AIMS: The aim of the present ALERT (Assessment of Lescol in Renal Transplantation) study is to determine whether renal transplant recipients would also benefit from statin therapy. ALERT is a multicentre, randomized, double-blind, placebo-controlled trial to assess the effect of fluvastatin in renal transplant recipients with mild-to-moderate hypercholesterolaemia. The primary objective is to investigate the effects of fluvastatin on major adverse cardiac events (MACE). In addition, the effects on cardiovascular and all-cause mortality, as well as renal function, will be addressed. STUDY POPULATION: The study population contains patients with functioning renal allografts of more than 6 months' duration, recruited from 75 centres in Northern Europe and Canada. Patients of both sexes, aged 30-75 years, with a total cholesterol level of 4.0-9.0 mmol/l (155-348 mg/dl) were included, except for those with a history of myocardial infarction, where the upper limit for inclusion was 7.0 mmol/l (270 mg/dl). STUDY DESIGN: A total of 2100 patients were recruited by the end of October 1997 and will be followed for up to 6 years. This report presents the design features of the study (recruitment, follow-up, sample size, data analysis and study organization), along with baseline results. ALERT is the first large-scale prospective, randomized, double-blind study to address the prevention of cardiovascular mortality in renal transplant patients receiving an HMGCoA reductase inhibitor.