title: Association between calcineurin inhibitor treatment and peripheral nerve dysfunction in renal transplant recipients.
abstract: Neurotoxicity is a significant clinical side effect of immunosuppressive treatment used in prophylaxis for rejection in solid organ transplants. This study aimed to provide insights into the mechanisms underlying neurotoxicity in patients receiving immunosuppressive treatment following renal transplantation. Clinical and neurophysiological assessments were undertaken in 38 patients receiving immunosuppression following renal transplantation, 19 receiving calcineurin inhibitor (CNI) therapy and 19 receiving a calcineurin-free (CNI-free) regimen. Groups were matched for age, gender, time since transplant and renal function and compared to normal controls (n = 20). The CNI group demonstrated marked differences in nerve excitability parameters, suggestive of nerve membrane depolarization (p < 0.05). Importantly, there were no differences between the two CNIs (cyclosporine A or tacrolimus). In contrast, CNI-free patients showed no differences to normal controls. The CNI-treated patients had a higher prevalence of clinical neuropathy and higher neuropathy severity scores. Longitudinal studies were undertaken in a cohort of subjects within 12 months of transplantation (n = 10). These studies demonstrated persistence of abnormalities in patients maintained on CNI-treatment and improvement noted in those who were switched to a CNI-free regimen. The results of this study have significant implications for selection, or continuation, of immunosuppressive therapy in renal transplant recipients, especially those with pre-existing neurological disability.
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Arnold
authors.forename: B A
authors.initials: BA
authors.lastname: Pussell
authors.forename: T J
authors.initials: TJ
authors.lastname: Pianta
authors.forename: C S-Y
authors.initials: CS
authors.lastname: Lin
authors.forename: M C
authors.initials: MC
authors.lastname: Kiernan
authors.forename: A V
authors.initials: AV
authors.lastname: Krishnan
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D003430:Cross-Sectional Studies; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus
keywords: Calcineurin inhibitors; nerve excitability; neuropathy; renal transplant