title: Long-term clinicopathological impact of calcineurin inhibitor cessation without specific cytoreductive induction in kidney transplantation.
abstract: Calcineurin inhibitors (CNIs) have considerably improved renal allograft survival. However, their chronic use has various adverse effects, including hypertension, hyperlipidemia, and nephrotoxicity. We conducted a retrospective study of kidney transplant recipients using a CNI withdrawal protocol. Eleven of 13 patients who had stable graft function on triple-drug therapy including a cyclosporine (CsA) were enrolled in this study. The dose of CsA was reduced by 20% every two wks until complete withdrawal. The mean period between the baseline and last biopsies was 97 (range: 21-123) months. No patient had an acute rejection episode during follow-up. Progression of interstitial fibrosis and tubular atrophy was seen in five and six cases, respectively. Arteriolar hyalinosis improved in three cases, but worsened in four. No patient lost his graft during the study. The mean serum creatinine level was 1.30 ± 0.26 mg/dL at baseline and stable for 10 yr after elimination (1.26 ± 0.11 mg/dL). At the end of the study, four of the eleven patients had reduced their antihypertensive drugs, and one patient had stopped hyperlipidemia treatment. CNI withdrawal can be implemented safely in stable renal transplant recipients and might lead to improved patient outcomes. Additional specific evidence of CNI nephrotoxicity should be elucidated.
authors.affiliation: Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tatsu
authors.initials: T
authors.lastname: Tanabe
authors.forename: Ken
authors.initials: K
authors.lastname: Morita
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fujita
authors.forename: Kanako
authors.initials: K
authors.lastname: Hatanaka
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hirose
authors.forename: Hajime
authors.initials: H
authors.lastname: Sasaki
authors.forename: Daiki
authors.initials: D
authors.lastname: Iwami
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hotta
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nonomura
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D008775:Methylprednisolone
keywords: calcineurin inhibitor; kidney transplantation; pathology; toxicity