title: Monitoring of mycophenolic acid and kidney function during combined immunosuppressive therapy.
abstract: BACKGROUND
  Mycophenolic acid (MPA), a selective inhibitor of lymphocyte proliferation, has lately been used to improve renal function and prolong graft survival in renal transplanted patients. Still, there is no consensus considering the recommended dosing and the therapeutic range of MPA.
  
  
  METHODS
  To estimate the safe therapeutic range of MPA, its plasma level and indicators of kidney function were measured in 216 patients (138 male, 78 female, age 46 ± 12 years) 67 ± 46 months after transplantation. Besides MPA, patients received cyclosporine (Group A, n=122) or tacrolimus (Group B, n=77). Seventeen patients (Group C) were treated with MPA in combination with everolimus or sirolimus. Plasma MPA was measured by enzyme inhibition assay.
  
  
  RESULTS
  In the whole study group MPA level increased with the dose of MPA (p=0.013). MPA level was below the therapeutic range in 40% (Group A) and 45% (Group B) of patients, respectively. MPA was 1.9 ± 1.56 mg/L in Group A, 2.4 ± 1.69 mg/L in Group B. In Group A MPA level increased and cyclosporine decreased with the progress of renal disease.
  
  
  CONCLUSIONS
  Increasing MPA/cyclosporine ratio at more severe stages of chronic kidney disease was tolerable for the patients and rejection could be avoided. Tubular damage detected by urinary N-acetyl-β-D-glucosaminidase did not correlate with the MPA level.
authors.affiliation: Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. olaha@dote.hu
authors.forename: Anna V
authors.initials: AV
authors.lastname: Oláh
authors.forename: László
authors.initials: L
authors.lastname: Asztalos
authors.forename: Gergely
authors.initials: G
authors.lastname: Ivády
authors.forename: Eva
authors.initials: E
authors.lastname: Varga
authors.forename: Agota M
authors.initials: AM
authors.lastname: Kovács
authors.forename: János
authors.initials: J
authors.lastname: Kappelmayer
authors.forename: József
authors.initials: J
authors.lastname: Varga
mesh_terms: D000118:Acetylglucosaminidase / Q000032:analysis / Q000378:metabolism; D000328:Adult; D019540:Area Under Curve; D001681:Biological Assay; D049109:Cell Proliferation / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D016903:Drug Monitoring / Q000379:methods*; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000032:analysis / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D000118:Acetylglucosaminidase; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus