title: A single-centre, open-label, prospective study of an initially short-term intensified dosing regimen of enteric-coated mycophenolate sodium with reduced cyclosporine A exposure in Chinese live-donor kidney transplant recipients.
abstract: OBJECTIVE
  The nephrotoxicity of cyclosporine A (CsA) accounts for dysfunction of kidney allografts in the clinic. Short-term intensified dosing using enteric-coated mycophenolate sodium (EC-MPS) may facilitate CsA sparing after kidney transplantation without compromising safety.
  
  
  METHODS
  In a 12-month, single-centre open-label prospective trial, 180 de novo live-donor kidney transplant recipients at low-immunological risk were randomised to a low-dose cyclosporine group which received a low dose of cyclosporine, short-term intensified EC-MPS dosing (2160 mg/day to week 6, 1440 mg/day thereafter) and corticosteroids or a standard-dose cyclosporine group which received a standard dose of cyclosporine, standard EC-MPS dosing (1440 mg/day) and corticosteroids. The primary end-point [treatment failure including biopsy-proven acute rejection (BPAR), graft loss, death], secondary end-point and adverse events were monitored.
  
  
  RESULTS
  The primary end-point (treatment failure) occurred in 13.3% (12/90) of the low-dose cyclosporine group and 16.7% (15/90) of the standard-dose cyclosporine group (p = 0.53) (difference -3.4%, 95% confidence interval -11.7% to 7.5%, based on a noninferiority margin of 20%). BPAR occurred in 11.1% and 13.3% of patients in the low-dose cyclosporine group and standard-dose cyclosporine group, respectively (p = 0.65). The estimated glomerular filtration rate, as calculated by the Cockcroft-Gault formula, was similar at 12 months after transplantation (low-dose cyclosporine group 63 ± 19 ml/min/1.73 m(2) and standard-dose cyclosporine group 59 ± 15 ml/min/1.73 m(2) ; p = 0.43). The levels of serum creatinine and occurrence of adverse events between the two groups were not statistically different.
  
  
  CONCLUSIONS
  A regimen of early intensified EC-MPS dosing permits low-dose cyclosporine in live-donor kidney transplant patients at low-immunological risk without compromising efficacy at 12 months' follow-up.
authors.affiliation: The Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Ministry of Health and Key Laboratory of Ministry of Education, Wuhan, China; Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: L
authors.initials: L
authors.lastname: Cai
authors.forename: F
authors.initials: F
authors.lastname: Zeng
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Wei
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002681:China; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011446:Prospective Studies; D013997:Time Factors; D066027:Transplant Recipients; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid