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

Published on Mar 1, 2000in Nephrology Dialysis Transplantation4.198
· DOI :10.1093/ndt/15.3.324
Volker Nickeleit11
Estimated H-index: 11
Hans H. Hirsch60
Estimated H-index: 60
(University of Basel)
+ 4 AuthorsMichael J. Mihatsch72
Estimated H-index: 72
(University of Basel)
We review BK-virus nephropathy (BKN ) as Introduction a new complication that increasingly aVects renal allo- grafts and causes dysfunction. Since starting in 1996, Manifest polyomavirus infection of renal allografts we have seen 11 cases. Currently, the prevalence of with the BK-virus strain, i.e. BK-virus nephropathy BKN is 3% in our graft biopsies. The diagnosis can (BKN ), is an unusual complication that has recently only be made histologically. The virus aVects tubular been described (1-3). BKN causes severe graft dysfunc- epithelial cells that show characteristic intranuclear tion and contributes to graft loss (3-5). inclusion bodies. The major reason for impaired graft Polyomavirus (PV ), a subgroup of the papovavirus function and a possible way for viral particles to gain family, is a double stranded non-enveloped DNA virus access to the blood via peritubular capillaries is necrosis (6 ). Primary infection usually occurs early in life of infected epithelial cells. BK-virus DNA in the without clinical symptoms (6 ). PV frequently remains plasma, which can be detected by PCR, is closely in a dormant state in the kidneys and ureters of healthy, associated with nephropathy. BK-virus does not stimu- immunocompetent individuals (7-9). Immuno- late tubular MHC-class II expression as judged by compromised patients, however, have an increased immunofluorescence double labelling. The inflamma- risk of developing clinically manifest PV infection. tory response is inconsistent and the frequency of Human disease can be caused by two PV strains: JC rejection episodes is not increased during disease. and BK. JC-virus causes progressive multifocal leuko- Clinical manifestation of viral nephropathy evolves in encephalopathy (6,10). BK-virus is associated with several stages. (i) Initial, asymptomatic and reversible changes in the kidney (2,11) and, as proposed by some activation of the virus, judged by the presence of authors, with haemorrhagic cystitis and ureteral sten- inclusion bearing cells in the urine. (ii) High dose osis (12,13). Although immunosuppression increases immunosuppressive drug regimens, often including tac- the probability of latent BK-virus reactivation, clinical rolimus. (iii) Tubular injury and viraemia as additional manifestation of disease is rare. promoting conditions. BKN nephropathy was associ- In Basel we did not diagnose a single case of BKN ated with graft loss in 45% of our patients. The before 1996, even during previous high-dose cyclospo- remaining patients with persistent viral nephropathy rin therapy protocols (personal observation). However, showed renal dysfunction (serum creatinine levels on 10 patients with a total of 23 tissue samples were average 150% above baseline readings). Currently, no encountered in the following 3 years (current preval- established antiviral therapy is available. We discuss ence in transplant biopsies 3.1%, current prevalence in attempts to lower immunosuppression as a means to transplant recipients 4.5%). The prevalence in our control viral replication. We propose a diagnostic centre is similar to that recently reported by algorithm for screening and monitoring the disease. Drachenberg et al. (4). In comparison, a manifest CMV infection had been diagnosed in only 11 patients with a total of 16 graft biopsies over the past 32 years
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