title: Calcineurin inhibitors in HLA-identical living related donor kidney transplantation.
abstract: BACKGROUND
  Given the nephrotoxicity of calcineurin inhibitors (CNIs), we asked whether their addition improved living related donor (LRD) human leukocyte antigen (HLA) identical kidney transplant recipient outcomes.
  
  
  METHODS
  We performed a comprehensive literature review and a single-center study comparing patient survival (PS) and graft survival (GS) of LRD HLA-identical kidney transplants for three different immunosuppression eras: Era 1 (up to 1984): anti-lymphocyte globulin (ALG) induction and maintenance immunosuppression with prednisone and azathioprine (AZA) (n = 114); Era 2a (1984-99): CNI added; evolution from ALG to thymoglobulin; AZA to mycophenolate (n = 262). Era 2b (1999-2011): rapid discontinuation of prednisone (thymoglobulin induction, CNI and mycophenolate) in recipients having first or second transplant and not previously on prednisone (n = 77).
  
  
  RESULTS
  Demographics differed by era: recipient (P < 0.0001) and donor age (P < 0.0001) increased and the proportion of Caucasian donors (P = 0.02) and recipients (P = 0.003) decreased with each advancing era. There was no significant difference in PS (P = 0.6); cause of death (P = 0.5); death-censored GS (P = 0.8) or graft loss from acute rejection by era. Graft loss from chronic allograft nephropathy (P = 0.02) and hypertension (P = 0.005) were greater in the CNI eras. There were no significant differences in the 1/creatinine slopes between eras for the first (P = 0.6), second (P = 0.9) or >2 years post-transplant (P = 0.4). Literature review revealed no clear benefits for CNI in these human leukocyte antigen (HLA) identical LRD graft recipients.
  
  
  CONCLUSIONS
  This study confirmed that there are no benefits of CNIs for HLA-identical LRD recipients. Moreover, we did find evidence of potential harm. Thus, monotherapy or early discontinuation of CNI should be given consideration in these patients.
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Priya S
authors.initials: PS
authors.lastname: Verghese
authors.forename: Ty B
authors.initials: TB
authors.lastname: Dunn
authors.forename: Srinath
authors.initials: S
authors.lastname: Chinnakotla
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Gillingham
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Matas
authors.forename: Michael S
authors.initials: MS
authors.lastname: Mauer
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000276:immunology; D001379:Azathioprine / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D002648:Child; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000401:mortality; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D065095:Calcineurin Inhibitors; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D001379:Azathioprine; D016559:Tacrolimus
keywords: HLA identical; calcineurin inhibitors; cyclosporine; renal transplant; tacrolimus