mmf and calcineurin inhibitor withdrawal in can

Conditions: Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation

Summary: prospective, randomised study: effect of mycophenolatmofetil (mmf) and cni withdrawal in patients with histologically proven chronic allograft nephropathy indication: change in immunosuppressive treatment of chronic allograft nephropathy (can)after renal transplantation hypothesis: antimetabolite mmf is able to stop progression of can and improve blood pressure/ metabolic parameters and structural vessel wall changes primary target:effects of cni withdrawal and mmf on renal function: stabilisation and/or improvement secondary targets: incidence of adverse events evaluation of the calcineurin inhibitor free mmf treatment effects on blood pressure, lipids, glucose metabolism and on structural and functional vesselwallchanges method:open prospective, randomized two-tailed, monocentric study

prospective, randomised study: effect of mycophenolatmofetil in patients with histologically proven chronic allograft nephropathy synopsis indication: change in treatment to improve the course of chronic allograft nephropathy method: open prospective, randomized two-tailed, non blinded monocentric study follow up period: 35 weeks number of patients: 2 x 86 patients inclusion criteria: • written informed consent * reduction of graft function: increase of serum creatinine \>/= 0,1mg/dl/month in the previous 6 months before start of the study and/or new occurrence or increasing proteinuria in the last 6 months before start of the study * serum creatinine \< 4 mg/dl * biopsy within the last 3 months * histologically proved chronic allograft nephropathy (graft glomerulopathy, chronic rejection ,interstitial fibrosis, tubular atrophy, vascular arteriosclerosis,hyalinosis) * \>1 year after renal allografting * at least 5 mg/day of prednisolone or equivalent dose exclusion criteria: • malignomas * gravidity or lactation * participation in other studies * severe infections * florid gastrointestinal ulcer * age between 18 and 70 years * leukopenia with less that 3000/l leucocytes, anaemia hb  9 g/dl * therapy with mycophenolatmofetil in the past 6 months * acute rejections in the apst 6 months study protocol: phase i: week 1.-3. conversion to triple-drug-therapy, consisting of mycophenolatmofetil, corticosteroids (e.g. prednisolone) and ciclosporine a or tacrolimus 1. addition of mycophenolatmofetil (mmf) to the previous immosuppressive treatment, consisting of ciclosporine a (csa) or tacrolimus (fk506) in combination with corticosteroids, e.g. prednisolone (p). in the case that azathioprine (aza) had been given, aza is replaced by mmf. the therapy with mmf starts 3 days after the elimination of azathioprine. the addition of mmf follows the following scheme if nothing else is indicated: 1. week: 1g/day, 2.week: 1,5g/day, 3.week: 2g/day 2. ciclosporine a bzw. tacrolimus: target whole trough blood levels: csa: 80-120 ng/ml (hplc) fk506: 4-7 ng/ml (imx tacrolimus, abbott) 3. corticosteroids, e.g. prednisolone: the previous dosage is continued, but at least 5 mg prednisolone/day (or equivalent) must be given phase ii: week 4.-9. randomisation at the beginning of week 4: all patients receiving at least 3 x 500 mg mmf per day were randomised as follows group a: continuation of the triple therapy group b: elimination of csa bzw. fk506 the ciclosporine a- or tacrolimus-dosage is reduced ba 33% each 2 weeks so that after 6-8 weeks a total elimination of the drugs is reached. phase iii: week 10.-35. continuous therapy with...: group a: triple therapy mmf / csa bzw. fk506 / corticosteroids e.g. prednisolone group b: dual therapy mmf / corticosteroids e.g. prednisolone primary endpoint: comparison of the development of 1/creatinine in both branches 32 weeks after randomization secondary endpoints: * occurrence of... * acute rejections * infections * malignomas * gastrointestinal disorders * blood pressure evolution and number of antihypertensive drugs * changes concerning the lipid state * changes concerning the glucose metabolism * changes in metabolism of uric acid * comparison of the development of 1/creatinine within each branch 6 months before and 6 months after therapy conversion * comparison of drop out rate in branches a und b * pharmacokinetics of mycophenolic acid (mpa) based on a new method of abbreviated area under the curve (auc) determination * vessel wall changes of the carotid arteries measured by high resolultion ultrasound methods and hemodynamic parameters measured by task force equipment before and 9 month after cni withdrawal and mmf addition criteria for study discontinuation: * sepsis * occurrence of acute rejections * graft loss * other severe adverse events * patients decision

Eligibility criteria:
inclusion criteria: written informed consent reduction of graft function: increase of serum creatinine \>= 0,1mg/dl/month in the previous 6 months before start of the study and/or new occurrence or increasing proteinuria in the last 6 months before start of the study serum creatinine \ =1 year after renal allografting \>=5 mg/day prednisolone or equivalent dose exclusion criteria: malignomas gravidity or lactation participation in other studies severe infections gastrointestinal ulcer age \ 70 years leukopenia with less that 3000/dl leucocytes, anaemia hb \> 9 g/dl therapy with mycophenolatmofetil in the past 6 months acute rejections in the past 6 months -

Keywords: kidney failure, chronic kidney transplantation