Document Detail

Pharmacodynamic monitoring of cyclosporine a in renal allograft recipients shows a quantitative relationship between immunosuppression and the occurrence of recurrent infections and malignancies.
MedLine Citation:
PMID:  17130775     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: At present it is unclear which dose and consecutive blood levels of cyclosporine A (CsA) are optimal with respect to immunosuppressive efficacy and drug specific side effects at the level of individual patients. Several pharmacodynamic measures of CsA effects have been proposed, but have not become clinical routine yet. Besides the lack of practicability, the biological relevance of these assays has not been determined so far. METHODS: Residual expression of nuclear factor of activated T-cells (NFAT)-regulated genes two hours after drug intake was used as molecular pharmacodynamic marker to assess CsA effects on lymphocytes and correlated with the frequency of recurrent infections and malignancies in patients with five or more years of follow-up posttransplantation. RESULTS: Recurrent infectious complications were observed in 44% and malignancies in 20% of the 133 patients studied. Patients with a strong suppression of NFAT-regulated genes by CsA--as judged by a residual level of transcription of less than 15% after drug intake--develop more frequent infections (53% vs. 29%; P = 0.005) and malignancies (22% vs. 4%; P = 0.002). The lack of correlation between the incidence of these complications and CsA blood concentration might point to the interindividual differences in the sensitivity towards calcineurin inhibition. CONCLUSION: The data presented here reveal a clear relation between the frequency of infectious and malignant complications and the degree of suppression of NFAT-regulated genes by CsA in transplanted patients. Therefore, pharmacodynamic monitoring of CsA efficacy in transplanted patients might be a useful tool to adjust immunosuppressive therapy in individual patients.
Claudia Sommerer; Mathias Konstandin; Thomas Dengler; Jan Schmidt; Stefan Meuer; Martin Zeier; Thomas Giese
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation     Volume:  82     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-11-28     Completed Date:  2007-01-23     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1280-5     Citation Subset:  IM    
Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
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MeSH Terms
Analysis of Variance
Cyclosporine / blood,  pharmacokinetics*,  therapeutic use
Drug Monitoring
Gene Expression Regulation
Granulocyte-Macrophage Colony-Stimulating Factor / genetics
Immunosuppressive Agents / blood,  pharmacokinetics,  therapeutic use
Infection / epidemiology*
Interferon-gamma / genetics
Interleukin-2 / genetics
Kidney Transplantation / immunology,  physiology*
Middle Aged
NFATC Transcription Factors / genetics
Neoplasms / epidemiology*
Postoperative Complications / epidemiology*
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Interleukin-2; 0/NFATC Transcription Factors; 59865-13-3/Cyclosporine; 82115-62-6/Interferon-gamma; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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