title: Withdrawal of cyclosporine or tacrolimus after addition of mycophenolate mofetil in patients with chronic allograft nephropathy.
abstract: There has been a need for a prospective, randomized, controlled trial to determine whether the addition of mycophenolate mofetil (MMF) to a calcineurin inhibitor (CNI)-based regimen or MMF addition followed by CNI withdrawal is an effective treatment for chronic allograft nephropathy (CAN). We conducted the first randomized, prospective study to compare the introduction of MMF with or without CNI withdrawal in long-term transplant recipients with histologically proven CAN and deteriorating renal function. The primary endpoint was renal function as indicated by the slope of the inverse serum creatinine vs. time at 32 weeks after randomization. After an interim analysis found a greater-than-expected difference between groups in the slopes of the inverse serum-creatinine, the study was stopped for ethical reasons. There were 20 patients in the MMF/CNI continuation and 19 patients in the MMF/CNI withdrawal groups (mean time post-transplant 7 years). Renal function improved in the dual-therapy compared with the triple-therapy group (p=0.002). Blood pressure decreased in the dual-therapy group with a significant difference between groups at 35 weeks (p=0.04). No acute rejections occurred. Long-term patients with CAN experience a significant improvement in renal function and blood pressure when CNIs are replaced by MMF.
authors.affiliation: Department of Internal Medicine D, University of Muenster, Muenster, Germany. suwelac@uni-muenster.de
authors.forename: Barbara
authors.initials: B
authors.lastname: Suwelack
authors.forename: Ulf
authors.initials: U
authors.lastname: Gerhardt
authors.forename: Helge
authors.initials: H
authors.lastname: Hohage
mesh_terms: D000328:Adult; D001794:Blood Pressure; D015992:Body Mass Index; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011446:Prospective Studies; D011897:Random Allocation; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid; D016559:Tacrolimus