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Review
. 2014 Jan;29(1):209-18.
doi: 10.1093/ndt/gft447.

Calcineurin inhibitors in HLA-identical living related donor kidney transplantation

Priya S Verghese  1 , Ty B Dunn, Srinath Chinnakotla, Kristin J Gillingham, Arthur J Matas, Michael S Mauer
Affiliations
Review

Calcineurin inhibitors in HLA-identical living related donor kidney transplantation

Priya S Verghese et al. Nephrol Dial Transplant. 2014 Jan.

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.

Keywords: HLA identical; calcineurin inhibitors; cyclosporine; renal transplant; tacrolimus.

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Figures

FIGURE 1:
FIGURE 1:
Patient survival by era.
FIGURE 2:
FIGURE 2:
Death-censored graft survival by era.
FIGURE 3:
FIGURE 3:
Acute rejection-free survival by era.
See this image and copyright information in PMC

References

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