title: Resolution of neurotoxicity and beta-cell toxicity in an islet transplant recipient following substitution of tacrolimus with MMF.
abstract: Calcineurin inhibitors such as tacrolimus have well-recognized efficacy in organ transplantation but side effects of nephrotoxicity, neurotoxicity, and beta-cell toxicity that can be particularly detrimental in islet transplantation. Neuro- and nephrotoxicity have been demonstrated in multiple islet transplant recipients despite the relatively low serum maintenance levels typically used (3-5 ng/ml). We describe a single patient in whom symptoms and signs of neurotoxicity necessitated substitution of tacrolimus with mycophenolate mofetil (MMF), which resulted in complete symptom resolution over the subsequent 9 months. Concomitantly noted were an almost immediate improvement in glycemic control and an improved response to stimulation testing, suggesting remission of tacrolimus-induced beta-cell toxicity and insulin resistance. At 18 months post-"switch," 30 months posttransplant, the patient remains insulin independent with good glycemic control. The goal to remove calcineurin inhibitors from regimens of islet transplantation is a worthy one.
authors.affiliation: Diabetes Research Institute, University of Miami School of Medicine, Miami, FL 33136, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Froud
authors.forename: David A
authors.initials: DA
authors.lastname: Baidal
authors.forename: Gaston
authors.initials: G
authors.lastname: Ponte
authors.forename: Jacqueline V
authors.initials: JV
authors.lastname: Ferreira
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Alejandro
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology; D012307:Risk Factors; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use; D016559:Tacrolimus / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus