title: Tacrolimus reduction with everolimus addition for calcineurin inhibitor-induced arteriolopathy in kidney allografts.
abstract: OBJECTIVE
  The aim of this study was to evaluate the effect of tacrolimus (TAC) reduction with everolimus (EVR) addition on the maintenance immunosuppression for the recipients with calcineurin inhibitor arteriolopathy (CNIA).
  
  
  METHODS
  This retrospective study consisted of 13 kidney allograft recipients who were found to have CNIA on protocol biopsy specimens. The time of intervention was 9-89 months. All the patients were on TAC, mycophenolate mofetil (MMF). 9 of 13 were on steroid. EVR was added and TAC dose was reduced. MMF dose was not changed. Revaluation biopsy was taken 12 months after the intervention. TAC trough levels (TACC0 , ng/mL), EVR trough levels (EVRC0 , ng/mL), estimated glomerular filtration rate (eGFR, mL/min), and urine protein per creatinine (uP/Cr, g/g creatinine) were compared before and 1 year after intervention. Changes in pathological findings and adverse events were also reviewed.
  
  
  RESULTS
  Aah scores improved in 5 patients. Aah scores did not change in the rest of the patients. No deterioration was observed. No improvement was seen in those with aah3. TACC0 reduced from 3.3 to 2.3. EVRC0 at revaluation was 4.1. eGFR improved from 44.3 to 49.8. uP/Cr slightly increased from 0.20 to 0.26. EVR was discontinued in 1 patient due to an adverse event. EVR dose was reduced in 5 patients due to adverse events.
  
  
  CONCLUSIONS
  TAC reduction with EVR addition improves CNIA histologically in selected cases.
authors.affiliation: Department of Renal Transplant Surgery and Urology, Sapporo Hokuyu Hospital, Sapporo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Miura
authors.affiliation: Department of Renal Transplant Surgery and Urology, Sapporo Hokuyu Hospital, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Higashiyama
authors.affiliation: Department of Pathology, Sapporo City General Hospital, Sapporo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fukasawa
authors.affiliation: Department of Nephrology, Sapporo Hokuyu Hospital, Sapporo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Department of Renal Transplant Surgery and Urology, Sapporo Hokuyu Hospital, Sapporo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tamaki
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D001160:Arterioles / Q000187:drug effects* / Q000473:pathology; D050379:Arteriolosclerosis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D001706:Biopsy; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D018450:Disease Progression; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000008:administration & dosage*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D020127:Recovery of Function; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D016559:Tacrolimus
keywords: arteriolopathy; everolimus; histopathology; tacrolimus