Polyomavirus nephropathy: Pathogenesis, morphological and clinical aspects

The polyoma-BK-virus strain was said to be "in search" of a disease. The search is finally over. Since the mid 1990ies, when new third generation immunosuppressive drug regimens were introduced into the routine management of renal allograft recipients, the polyoma-BK-virus (allograft) nephropathy (BKN) has gained increasing clinical interest. BKN is currently the most common infection affecting renal allografts with a prevalence of 1% up to 10% reported in various transplant centers world-wide. It can lead to chronic allograft dysfunction and eventual graft loss in more than 50% of cases (observed in some institutions). BKN is most likely caused by the reactivation of latent BK viruses which enter under sustained and intensive immunosuppression into a productive and lytic replicative cycle. BKN is typically limited to the kidney transplant. It is histologically defined by the presence of intranuclear viral inclusion bodies in tubular and parietal glomerular epithelial cells. Different variants of polyomavirus inclusion bodies (types I through 4) and adjunct techniques [immunohistochemistry, electron microscopy and polymerase chain reaction (PCR)] that are used for proper characterization are described. Virally induced severe tubular injury is the morphologic correlate for the clinically observed allograft dysfunction. Special emphasis is placed on the pathogenesis leading from latent to productive BK-Virus infections and on the clinical and pathophysiological significance of different histological stages of BKN. Risk factors promoting disease as well as clues to diagnose BKN and concurrent acute allograft rejection are discussed. The pathologist's role in patient management using the detection of polyomavirus inclusion bearing decoy cells in the urine, plasma PCR analyses, and graft biopsies is highlighted.