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Investigation of viral infections in kidney transplant recipients unveils the pathogenic role of Parvovirus B19 in chronic allograft injury

Abstract number: O38

Barzon L., Pacenti M., Biasolo M., Murer L., Palù G.

Objectives: The relevance of viral infection of the kidney allograft in the development of allograft lesions is still unclear, although some viruses have been implicated. Aim of this study is the investigation of both systemic and intrarenal viral infections in kidney transplant recipients and their association with the risk of acute rejection and chronic allograft injuries predictive of long-term dysfunction.

Methods: Screening for genome sequences of all human herpesviruses, polyomaviruses, and parvovirus B19 in baseline and 6, 12, 24 months follow-up allograft biopsies performed in 69 transplanted children. Correlation of virological findings with clinical data, viral DNAemia, renal function tests, and allograft histology.

Results: Overall, viral DNA was detectable in 46% baseline biopsies and in about 70% follow-up biopsies. The most frequently detected viruses were parvovirus B19 and HHV-6, already present in donor kidneys, and BKV and EBV, usually acquired during follow-up. In most cases, viral DNA persisted in the kidney allograft during follow-up. Univariate and multivariate cox-proportional hazard regression analysis demonstrated that, among viruses, only the intrarenal persistence of B19 DNA was significantly associated with the development of chronic allograft injury, whereas HCMV DNAemia, but not allograft infection, was a risk factor for acute rejection. Analysis of matched data on intrarenal viral DNA detection and DNAemia indicated that HCMV did not involve the kidney allograft in the course of systemic infection. Instead, B19 targeted the kidney, where it established prolonged infection. Both the early transcript NS1 and the late lytic transcripts VP1, VP-2, and 11kDa were expressed in biopsies from patients with primary acute infection and DNAemia, whereas only NS1 was expressed in biopsies from patients without DNAemia. These results indicate that, after acute infection, characterised by expression of all viral genes, B19 establishes persistent infection in the kidney, characterised by expression of the early gene NS1 only. Kidney injury might be linked to persistent B19 replication in the allograft, but also to expression of the pro-apoptotic NS1 protein.

Conclusions: Unprecedented so far, this study demonstrates that persistent intrarenal parvovirus B19 infection is associated with chronic allograft injury in kidney transplant recipients. Moreover, this study underlines the role of HCMV as risk factor for acute rejection.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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