Calcineurin inhibitors in HLA-identical living related donor kidney transplantation

Priya Verghese, Ty B Dunn, Srinath Chinnakotla, Kristin J. Gillingham, Arthur J Matas, Michael Mauer

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

BackgroundGiven 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.MethodsWe 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).ResultsDemographics 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.ConclusionsThis 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.

Original languageEnglish (US)
Pages (from-to)209-218
Number of pages10
JournalNephrology Dialysis Transplantation
Volume29
Issue number1
DOIs
StatePublished - Jan 2014

Bibliographical note

Funding Information:
This study was supported by a grant from the National Institutes of Health (DK013083). This study was partially presented as an abstract at the annual meeting of the 2013 American Transplant Congress in Seattle, WA, USA.

Keywords

  • HLA identical
  • calcineurin inhibitors
  • cyclosporine
  • renal transplant
  • tacrolimus

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