Faculty Collaboration Database

Calcineurin inhibitors in HLA-identical living related donor kidney transplantation. Nephrol Dial Transplant 2014 Jan;29(1):209-18

Date

01/15/2014

Pubmed ID

24414376

Pubmed Central ID

PMC3888312

DOI

10.1093/ndt/gft447

Scopus ID

2-s2.0-84892711071 (requires institutional sign-in at Scopus site)   15 Citations

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.

Author List

Verghese PS, Dunn TB, Chinnakotla S, Gillingham KJ, Matas AJ, Mauer MS

Author

Ty Blink Dunn MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Antilymphocyte Serum
Azathioprine
Calcineurin Inhibitors
Child
Creatinine
Cyclosporine
Female
Graft Rejection
Graft Survival
HLA Antigens
Humans
Immunosuppressive Agents
Kidney Transplantation
Living Donors
Male
Middle Aged
Tacrolimus
Young Adult