title: Does reduction in mycophenolic acid dose compromise efficacy regardless of tacrolimus exposure level? An analysis of prospective data from the Mycophenolic Renal Transplant (MORE) Registry.
abstract: Prospective data are lacking concerning the effect of reduced mycophenolic acid (MPA) dosing on efficacy and the influence of concomitant tacrolimus exposure. The Mycophenolic Renal Transplant (MORE) Registry is a prospective, observational study of de novo kidney transplant patients receiving MPA therapy under routine management. The effect of MPA dose reduction, interruption, or discontinuation (dose changes) was assessed in 870 tacrolimus-treated patients: 375 (43.1%) reduced tacrolimus (≤ 7 ng/mL at baseline) and 495 (56.9%) standard tacrolimus (>7 ng/mL); enteric-coated mycophenolate sodium 589 (67.7%) and mycophenolate mofetil 281 (32.3%). During baseline to month 1, months 1-3, months 3-6, and months 6-12, 9.3% (78/838), 16.6% (132/794), 20.7% (145/701), and 13.1% (70/535) patients, respectively, required MPA dose changes. These patients experienced an increased risk of biopsy-proven acute rejection at one yr with tacrolimus exposure either included in the model (hazard ratio [HR] 2.60, 95% CI 1.28-5.29, p = 0.008) or excluded (HR 2.58, 95% CI 1.28-5.23, p = 0.008). MPA dose changes were significantly associated with one yr graft failure when tacrolimus exposure was included (HR 2.23; 95% CI 1.01-4.89, p = 0.047) but not when tacrolimus exposure was excluded (HR 2.16; 95% CI 0.99-4.79; p = 0.054). These results suggest that reducing or discontinuing MPA can adversely affect graft outcomes regardless of tacrolimus trough levels.
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN 37232, USA. anthony.langone@vanderbilt.edu
authors.forename: Anthony
authors.initials: A
authors.lastname: Langone
authors.forename: Cataldo
authors.initials: C
authors.lastname: Doria
authors.forename: Stuart
authors.initials: S
authors.lastname: Greenstein
authors.forename: Mohanram
authors.initials: M
authors.lastname: Narayanan
authors.forename: Kimi
authors.initials: K
authors.lastname: Ueda
authors.forename: Bashir
authors.initials: B
authors.lastname: Sankari
authors.forename: Oleh
authors.initials: O
authors.lastname: Pankewycz
authors.forename: Fuad
authors.initials: F
authors.lastname: Shihab
authors.forename: Laurence
authors.initials: L
authors.lastname: Chan
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007674:Kidney Diseases / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage*; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012042:Registries; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus