title: Arteriosclerosis in zero-time biopsy is a risk factor for tacrolimus-induced chronic nephrotoxicity.
abstract: OBJECTIVE
  Calcineurin inhibitors reduce the acute rejection rate and greatly improve renal allograft survival. However, they are associated with some adverse events, including nephrotoxicity, a risk factor for allograft failure. Chronic calcineurin inhibitor-induced nephrotoxicity causes irreversible damage to renal components, such as arteriolar hyaline thickening. The aim of this study is to investigate the risk factors for tacrolimus-induced chronic nephrotoxicity using zero-time biopsy specimens.
  
  
  METHODS
  Between January 2001 and December 2010, 483 patients who underwent living-related kidney transplantation and had also been placed on a tacrolimus-based regimen were enrolled in this study. There were 1859 specimens evaluated comprising 483 zero-time biopsy specimens and 1376 protocol and for-cause biopsy specimens. De novo arteriolar hyaline thickening due to tacrolimus-induced chronic nephrotoxicity was scored according to the Banff classification aah score. In this study, tacrolimus-induced nephrotoxicity was defined as a positive aah score.
  
  
  RESULTS
  Of the 483 patients, 108 patients (22.4%) had biopsy-proven tacrolimus-induced chronic nephrotoxicity. Multivariate analysis showed that interlobular arteriosclerosis proven by zero-time biopsy (OR: 2.23, 95%CI: 1.38-3.58, P < 0.01) and acute rejection episodes (OR: 1.58, 95%CI: 1.00-2.47, P = 0.04) were independent risk factors for tacrolimus-induced chronic nephrotoxicity. However, tacrolimus-induced chronic nephrotoxicity did not affect long-term graft survival.
  
  
  CONCLUSIONS
  This is the first report showing that arteriosclerosis in zero-time biopsy specimens is a risk factor for histological tacrolimus-induced chronic nephrotoxicity.
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yagisawa
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Omoto
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
mesh_terms: D000208:Acute Disease; D000328:Adult; D064591:Allografts; D001160:Arterioles / Q000473:pathology; D001161:Arteriosclerosis / Q000150:complications* / Q000473:pathology; D001706:Biopsy; D065095:Calcineurin Inhibitors / Q000009:adverse effects*; D016009:Chi-Square Distribution; D002908:Chronic Disease; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: allograft; biopsy; calcineurin; nephrotoxicity; transplant