title: A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival, function, and protocol compliance at 1 year.
abstract: BACKGROUND
  In an attempt to reduce chronic calcineurin inhibitor induced allograft nephropathy in first cadaver and human leukocyte antigen non-identical living-donor renal transplantation, sirolimus (Siro) or mycophenolate mofetil (MMF) was tested as adjunctive therapy, with planned dose reductions of tacrolimus (Tacro) over the first year postoperatively. Adjunctive Siro therapy with a similar dose reduction algorithm for Neoral (Neo) was included for comparison.
  
  
  METHODS
  The detailed dose reduction plan (Tacro and Siro, group A; Tacro and MMF, group B; Neo and Siro, group C) is described in our companion report in this issue of Transplantation. The present report documents function, patient and graft survival, protocol compliance, and adverse events.
  
  
  RESULTS
  As mentioned (in companion report), group demographics were similar. The present study shows no significant differences in 1-year patient and graft survival but does show a trend that points to more difficulties in group C by way of a rising slope of serum creatinine concentration (P=0.02) and decreasing creatinine clearance (P=0.04). There were more patients who discontinued the protocol plan in group C. Thus far, no posttransplant lymphomas have appeared, and infectious complications have not differed among the groups. However, a greater percentage of patients in group C were placed on antihyperlipidemia therapy, with an (unexpected) trend toward a higher incidence of posttransplant diabetes mellitus in this group. Group A required fewer, and group B the fewest, antihyperlipidemia therapeutic interventions (P<0.00001).
  
  
  CONCLUSIONS
  This 1-year interim analysis of a long-term, prospective, randomized renal-transplant study indicates that decreasing maintenance dosage of Tacro with adjunctive Siro or MMF appears to point to improved long-term function, with reasonably few adverse events.
authors.affiliation: Department of Surgery, Division of Transplantation, University of Miami School of Medicine, Miami, FL 33101, USA. gciancio@med.miami.edu
authors.forename: Gaetano
authors.initials: G
authors.lastname: Ciancio
authors.forename: George W
authors.initials: GW
authors.lastname: Burke
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Gaynor
authors.forename: Adela
authors.initials: A
authors.lastname: Mattiazzi
authors.forename: David
authors.initials: D
authors.lastname: Roth
authors.forename: Warren
authors.initials: W
authors.lastname: Kupin
authors.forename: Maud
authors.initials: M
authors.lastname: Nicolas
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.forename: Anne
authors.initials: A
authors.lastname: Rosen
authors.forename: Joshua
authors.initials: J
authors.lastname: Miller
mesh_terms: D003404:Creatinine / Q000097:blood / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology* / Q000523:psychology; D008210:Lymphocele / Q000453:epidemiology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010349:Patient Compliance; D011183:Postoperative Complications / Q000145:classification / Q000453:epidemiology; D020123:Sirolimus / Q000627:therapeutic use*; D013530:Surgical Wound Infection / Q000453:epidemiology; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus