BK-virus nephropathy in renal transplants - tubular necrosis, MHC-class IIexpression and rejection in a puzzling game

We review BK-virus nephropathy (BKN) as a new complication that increasingl y 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 bo dies. The major reason for impaired graft function and a possible way for v iral particles to gain access to the blood via peritubular capillaries is n ecrosis 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 immunofluorescen ce double labelling. The inflammatory response is inconsistent and the freq uency of rejection episodes is not increased during disease. Clinical manif estation of viral nephropathy evolves in several stages. (i) Initial, asymp tomatic and reversible activation of the virus, judged by the presence of i nclusion 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 n ephropathy 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 con trol viral replication. We propose a diagnostic algorithm for screening and monitoring the disease.