title: Histopathologic impacts of everolimus introduction on kidney transplant recipients.
abstract: BACKGROUND
  Introduction of everolimus (RAD) has been established as a new immunosuppressive medication for kidney transplant (KT) recipients. Administration of RAD is capable of reducing the dosage of coadministrated calcineurin inhibitors (CNI). However, histological investigations have rarely been performed.
  
  
  METHODS
  To clarify histopathologic effects of RAD, a total of 9 adult KT recipients were enrolled (RAD group, n = 5; Mycophenolate mofetil (MMF) group, n = 4). Renal graft biopsies had been performed at 3 weeks and 1 year following KT.
  
  
  RESULTS
  There were no differences in 1-, 3-, and 5-year graft survival rates (RAD group: 100%, 100%, and 80%, respectively; MMF group: 100%, 100%, and 75%, respectively), and patient survival between the 2 groups (no deaths during the 5 years post-transplantation). Interestingly, although 2 patients in the RAD group had developed CNI nephrotoxicity clinically, renal biopsies had proven no CNI-related lesions 1 year later, which might be due to the reduction in CNI. On the other hand, 1 patient, in the MMF group, had been diagnosed histologically with new-onset CNI nephrotoxicity 1 year following KT. Importantly, the frequency and mean arteriolar hyalinosis (ah) scores, which reflect CNI nephrotoxicity, were significantly higher in the MMF group at 1-year biopsy (P < .05, P < .0001). Two patients in the RAD group improved their ah scores between 3 weeks and 1 year.
  
  
  CONCLUSIONS
  Pathological findings revealed that reversible CNI nephrotoxicity can be improved by RAD with reduced CNI maintenance therapy. It is reasonable to believe, therefore, that introduction of RAD is useful for patients who have been diagnosed with CNI nephrotoxicity.
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan. Electronic address: tsukasa@koto.kpu-m.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ushigome
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takata
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakao
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Harada
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Koshino
authors.affiliation: Department of Organ Interaction Research Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nobori
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan; Department of Organ Interaction Research Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000328:Adult; D001706:Biopsy; D065095:Calcineurin Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus