title: BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game.
abstract: We review BK-virus nephropathy (BKN) as a new complication that increasingly affects renal allografts and causes dysfunction. Since starting in 1996, we have seen 11 cases. Currently, the prevalence of BKN is 3% in our graft biopsies. The diagnosis can only be made histologically. The virus affects tubular epithelial cells that show characteristic intranuclear inclusion bodies. The major reason for impaired graft function and a possible way for viral particles to gain access to the blood via peritubular capillaries is necrosis of infected epithelial cells. BK-virus DNA in the plasma, which can be detected by PCR, is closely associated with nephropathy. BK-virus does not stimulate tubular MHC-class II expression as judged by immunofluorescence double labelling. The inflammatory response is inconsistent and the frequency of rejection episodes is not increased during disease. Clinical manifestation of viral nephropathy evolves in several stages. (i) Initial, asymptomatic and reversible activation of the virus, judged by the presence of inclusion bearing cells in the urine. (ii) High dose immunosuppressive drug regimens, often including tacrolimus. (iii) Tubular injury and viraemia as additional promoting conditions. BKN nephropathy was associated with graft loss in 45% of our patients. The remaining patients with persistent viral nephropathy showed renal dysfunction (serum creatinine levels on average 150% above baseline readings). Currently, no established antiviral therapy is available. We discuss attempts to lower immunosuppression as a means to control viral replication. We propose a diagnostic algorithm for screening and monitoring the disease.
authors.affiliation: Institute for Pathology, Institute for Medical Microbiology and Department of Nephrology, Kantonsspital, University of Basel, Basel, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Nickeleit
authors.forename: H H
authors.initials: HH
authors.lastname: Hirsch
authors.forename: M
authors.initials: M
authors.lastname: Zeiler
authors.forename: F
authors.initials: F
authors.lastname: Gudat
authors.forename: O
authors.initials: O
authors.lastname: Prince
authors.forename: G
authors.initials: G
authors.lastname: Thiel
authors.forename: M J
authors.initials: MJ
authors.lastname: Mihatsch
mesh_terms: D000818:Animals; D001739:BK Virus; D006084:Graft Rejection / Q000209:etiology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000382:microbiology*; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000473:pathology; D009336:Necrosis; D030361:Papillomavirus Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology; D011183:Postoperative Complications; D014412:Tumor Virus Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology
chemical_list: D000949:Histocompatibility Antigens Class II