Dataset Information

Risk factors for polyoma virus nephropathy.

ABSTRACT:

Background

Polyoma virus-associated nephropathy (PVN) is a common cause of renal transplant failure. The risk factors for the development of PVN have not yet been studied in large cohorts of patients for periods of 20 years.

Methods

We collected clinical, renal biopsy and urinary cytology data from all patients with renal transplantations performed at the University Hospital of Basel from 1985 to 2005. All patients with a renal biopsy and urine cytology were included (n = 880). Renal transplants were divided into three groups, according to evidence of polyoma virus (PV) infection (decoy cells in the urine) and biopsy-proven PVN: Renal transplants without evidence of a PV infection (n = 751). Renal transplants with PV reactivation, e.g. decoy cell (DC) found by urinary cytology, but without PVN (n = 90). Renal transplants with PVN (n = 39).

Results

The prevalence of biopsy-proven PVN in this cohort of patients was 3.3%. Immunosuppression with mycophenolate and/or tacrolimus, ATGAM, male gender of the recipient and a higher number of transplant rejection episodes were factors significantly associated with PVN development.

Conclusions

The most important risk factors for the development of PVN are acute rejection and ATGAM used as induction therapy as well as tacrolimus and mycophenolate as maintenance therapy. Therefore, we conclude that patients with tacrolimus and mycophenolate maintenance therapy should be carefully monitored for the development of PVN.

SUBMITTER: Prince O

PROVIDER: S-EPMC2644630 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Publications

Risk factors for polyoma virus nephropathy.

Prince Olivier O Savic Spasenija S Dickenmann Michael M Steiger Jürg J Bubendorf Lukas L Mihatsch Michael J MJ

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20081210 3

<h4>Background</h4>Polyoma virus-associated nephropathy (PVN) is a common cause of renal transplant failure. The risk factors for the development of PVN have not yet been studied in large cohorts of patients for periods of 20 years.<h4>Methods</h4>We collected clinical, renal biopsy and urinary cytology data from all patients with renal transplantations performed at the University Hospital of Basel from 1985 to 2005. All patients with a renal biopsy and urine cytology were included (n = 880). Re ...[more]

PMID: 19073658

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Project description:Virus infections can result in a range of cellular injuries and commonly this involves both the plasma and intracellular membranes, resulting in enhanced permeability. Viroporins are a group of proteins that interact with plasma membranes modifying permeability and can promote the release of viral particles. While these proteins are not essential for virus replication, their activity certainly promotes virus growth. Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease resulting from lytic infection of oligodendrocytes by the polyomavirus JC virus (JCV). The genome of JCV encodes six major proteins including a small auxiliary protein known as agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to viral propagation at various stages in the replication cycle, including transcription, translation, processing of late viral proteins, assembly of virions, and viral propagation. Previous studies from our and other laboratories have indicated that JCV agnoprotein plays an important, although as yet incompletely understood role in the propagation of JCV. Here, we demonstrate that agnoprotein possesses properties commonly associated with viroporins. Our findings demonstrate that: (i) A deletion mutant of agnoprotein is defective in virion release and viral propagation; (ii) Agnoprotein localizes to the ER early in infection, but is also found at the plasma membrane late in infection; (iii) Agnoprotein is an integral membrane protein and forms homo-oligomers; (iv) Agnoprotein enhances permeability of cells to the translation inhibitor hygromycin B; (v) Agnoprotein induces the influx of extracellular Ca(2+); (vi) The basic residues at amino acid positions 8 and 9 of agnoprotein key are determinants of the viroporin activity. The viroporin-like properties of agnoprotein result in increased membrane permeability and alterations in intracellular Ca(2+) homeostasis leading to membrane dysfunction and enhancement of virus release.

Dataset Information

Risk factors for polyoma virus nephropathy.

Background

Methods

Results

Conclusions

Publications

Risk factors for polyoma virus nephropathy.

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