title: Low-dose cyclosporine with mycophenolate mofetil induces similar calcineurin activity and cytokine inhibition as does standard-dose cyclosporine in stable renal allografts.
abstract: One strategy to minimize nephrotoxicity in maintenance immunosuppression in renal transplantation is reduction of cyclosporine (CsA) with addition of mycophenolate mofetil (MMF). This approach seems safe, but concern exists about whether it yields adequate immunosuppression in the long term. Thus, we investigated the pharmacodynamic response to CsA in stable renal allografts treated with standard CsA (n = 17, CsA-C0h > or = 125 ng/mL) and low CsA plus MMF (n = 18 CsA-C0h <100 ng/mL). Patients treated with MMF without CsA (n = 13) and healthy subjects (n = 7) were used as controls. We observed that inhibition of calcineurin (CN) activity in peripheral blood mononuclear cells (PBMC), as well as interleukin (IL)-2 and interferon (IFN)-gamma production were similar in Standard-CsA and Low-CsA+MMF groups. Moreover, addition of MMF to a low CsA dose regime improved the correlation between CsA-C2h and both CN activity and IL-2 production. Thus, our results suggest that MMF could be synergistic with the pharmacodynamic effect of low CsA in maintenance immunosuppression.
authors.affiliation: Nephrology Department, Hospital Universitari de Bellvitge, Barcelona, Spain. jgrinyo@csub.scs.es
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
authors.forename: Josep M
authors.initials: JM
authors.lastname: Cruzado
authors.forename: Olga
authors.initials: O
authors.lastname: Millán
authors.forename: Anna
authors.initials: A
authors.lastname: Caldés
authors.forename: Isabel
authors.initials: I
authors.lastname: Sabaté
authors.forename: Salvador
authors.initials: S
authors.lastname: Gil-Vernet
authors.forename: Daniel
authors.initials: D
authors.lastname: Serón
authors.forename: Mercé
authors.initials: M
authors.lastname: Brunet
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
authors.forename: Joan
authors.initials: J
authors.lastname: Torras
authors.forename: Jaume
authors.initials: J
authors.lastname: Martorell
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D065095:Calcineurin Inhibitors; D016207:Cytokines; D007376:Interleukin-2; D007371:Interferon-gamma; D016572:Cyclosporine; D009173:Mycophenolic Acid