Document Detail

Sirolimus therapy predisposes to new-onset diabetes mellitus after renal transplantation: a long-term analysis of various treatment regimens.
MedLine Citation:
PMID:  21693238     Owner:  NLM     Status:  In-Data-Review    
PURPOSE: This retrospective analysis evaluated the impacts of sirolimus (SRL), cyclosporine (CsA), and steroids (S) on the occurrence, treatment, and complications of new-onset diabetes after transplantation (NODAT).
METHODS: We compared 4 groups: group 1, SRL plus full-exposure CsA/S (n = 118); group 2, full-exposure CsA/S/no SRL ± antiproliferative drug (n = 141); group 3, SRL plus reduced CsA exposure/S (n = 212); and group 4, no SRL/full-exposure CsA/S ± antiproliferative drug (n = 43).
RESULTS: NODAT rates reflected the level of CsA exposure; at 10 years 54% versus 30% for groups 1 versus 2 (P = .0001); at 5 years 30% versus 21% for Groups 3 versus 4 (P = .3); 81% of cases were detected within 1 year. The lower NODAT rate in group 3 reflected a benefit of reduced CsA exposure (P = .02; hazard ratio (HR), 1.006). Group 1 showed higher CsA (P = .0001) and lower SRL concentrations (P = .016) versus group 3. CsA exposure closely correlating with NODAT among group 1 (P = .0001) was the major difference between groups 1 and 3 (P = .04; HR, 0.97). Differences in steroid treatment did not play a significant role in NODAT. Comparing groups 1 and 2, SRL was an independent risk factor for NODAT (P = .004; HR, 3.5).
CONCLUSIONS: Our 10-year experience revealed SRL to be an etiologic agent for NODAT, displaying interactive, possibly pharmacokinetic, and pharmacodynamic effects with concomitant CsA in combination treatment.
E Gyurus; Z Kaposztas; B D Kahan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation proceedings     Volume:  43     ISSN:  1873-2623     ISO Abbreviation:  Transplant. Proc.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0243532     Medline TA:  Transplant Proc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1583-92     Citation Subset:  IM    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Division of Immunology and Organ Transplantation, University of Texas Medical School, Houston, Texas.
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