title: A multicenter, randomized trial of increased mycophenolic acid dose using enteric-coated mycophenolate sodium with reduced tacrolimus exposure in maintenance kidney transplant recipients.
abstract: Mycophenolic acid (MPA) dose is frequently reduced in tacrolimus-treated kidney transplant patients, but alternatively the recommended MPA dose can be maintained with reduced tacrolimus exposure. In a 6-month, multicenter, randomized, openlabel study, maintenance kidney transplant patients receiving MPA (mycophenolate mofetil 1g/d or enteric-coated mycophenolate sodium (EC-MPS) 720 mg/d) and tacrolimus were randomized to convert to EC-MPS 1,440 mg/d with reduced tacrolimus (n = 46), or receive EC-MPS 720 mg/d with unchanged tacrolimus (n = 48). Mean estimated GFR (eGFR, aMDRD) at Month 6 was 49.1 ± 11.1 and 44.7 ± 11.5 ml/min/1.73 m2 in the EC-MPS 1,440 mg and 720 mg groups, respectively (p = 0.07). The primary endpoint, change in eGFR from Day 0 to Month 6, was 2.48 ± 0.95 ml/min/1.73 m2 with EC-MPS 1,440 mg and -0.48 ± 0.93 ml/min/1.73 m2 with EC-MPS 720 mg (difference 2.96 ml/min/1.73 m2; 95% CI 0.32 - 5.60; p = 0.028). There were no deaths, graft losses or acute rejections. Adverse events were more frequent with EC-MPS 1,440 mg than 720 mg (66.7% vs. 44.7%, p = 0.034). Adverse events with suspected relation to EC-MPS occurred in 26.7% and 21.3% of patients, respectively (p = 0.59). Conversion of kidney transplant patients to increased MPA dosing using EC-MPS 1,440 mg/d, with reduced tacrolimus exposure, appears an effective immunosuppression strategy and may improve renal function. Adverse events overall, but not those with a suspected relation to EC-MPS, were higher with ECMPS 1,440 mg/d.
authors.affiliation: Department of Nephrology, Dialysis and Organ Transplantation, Hôpital Rangueil, Toulouse, France. kamar.n@chu-toulouse.fr
authors.forename: Nassim
authors.initials: N
authors.lastname: Kamar
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cassuto
authors.forename: Florence
authors.initials: F
authors.lastname: Villemain
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Moal
authors.forename: Marc
authors.initials: M
authors.lastname: Ladrière
authors.forename: Benoît
authors.initials: B
authors.lastname: Barrou
authors.forename: Didier
authors.initials: D
authors.lastname: Ducloux
authors.forename: Kamel
authors.initials: K
authors.lastname: Chaouche
authors.forename: Stephane
authors.initials: S
authors.lastname: Quéré
authors.forename: Fabienne
authors.initials: F
authors.lastname: Di Giambattista
authors.forename: François
authors.initials: F
authors.lastname: Be
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D013608:Tablets, Enteric-Coated; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D003404:Creatinine; D009173:Mycophenolic Acid; D016559:Tacrolimus