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Clinical outcome with low-dose valacyclovir prophylaxis in high-risk renal transplant recipients: A 10-year experience
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
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Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-97644OAI: oai:DiVA.org:uu-97644DiVA: diva2:172665
Available from: 2008-10-29 Created: 2008-10-29 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Cytomegalovirus Infection in Immunocompetent and Renal Transplant Patients: Clinical Aspects and T-cell Specific Immunity
Open this publication in new window or tab >>Cytomegalovirus Infection in Immunocompetent and Renal Transplant Patients: Clinical Aspects and T-cell Specific Immunity
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cytomegalovirus (CMV) is a β-herpesvirus that, after primary infection, establishes a life-long persistence in the human host. Up to 90% of humans are infected with CMV, that is kept under control by CMV-specific CD8+ and CD4+ T cells. In patients with an impaired cellular immunity, however, CMV infections can be life-threatening. Thus, it is vital to identify risk factors and target high-risk patients. In this thesis we have evaluated low-dose valacyclovir prophylaxis in renal transplant patients and studied CMV-specific T cell immunity in healthy and renal transplant patients.

In renal transplant patients, the CMV serostatus of both the recipient (R) and the donor (D) has a major impact on the risk of developing CMV disease. In the high-risk D+/R- population, >50% are likely to develop CMV disease in the absence of prophylaxis and/or pre-emptive therapy. We have used low-dose valacyclovir prophylaxis for high-risk renal transplant patients, and graft and patient survival up to 5 years after transplantation was comparable to data reported for other prophylactic protocols. The incidence of CMV disease and graft rejection during the first year after transplantation was also comparable to that achieved with other protocols, and without the adverse effects reported for other therapies.

In the D+/R+ population, with a 15-35% risk of developing CMV disease, it is important to identify those individuals that are subject to a higher risk because of risk factors other than CMV serostatus. We therefore measured several immunologic parameters in renal transplant patients and in immunocompetent individuals with latent and primary CMV infection. In patients with a primary symptomatic CMV infection, CMV-specific CD8+ T cells peaked within a month after onset of symptoms but declined rapidly. In renal transplant patients, we found that the reduction in IFNγ-producing CMV-specific CD4+ T cells at 2 months post-transplantation may predict high-grade CMV DNAemia.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 87 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 386
Keyword
Cytomegalovirus, renal transplantation, cellular immunity, valacyclovir, mismatched, prophylaxis, tetramer, CD4 T cells, CD8 T cells
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-9324 (URN)978-91-554-7309-9 (ISBN)
Public defence
2008-11-29, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:15
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Available from: 2008-10-29 Created: 2008-10-29 Last updated: 2010-12-28Bibliographically approved

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