Morphological Spectrum of Polyoma Virus Disease in Renal Allografts: Diagnostic Accuracy of Urine Cytology

Abstract

The morphological features of polyoma virus disease (PVDz) in 571 concurrent urine and biopsy samples from 413 patients are described. In 54 patients PV was found in both biopsy and urine samples. Histologically, PV presented as: (a) mild, viral cytopathic/cytolytic changes, with absent or minimal inflammation involving isolated tubules; (b) moderate and severe, cytopathic/cytolytic changes associated with patchy or diffuse tubulo-interstitial inflammation and atrophy; (c) advanced, graft sclerosis with rare or absent viral cytopathic changes, indistinguishable from chronic allograft nephropathy. Histological progression from mild to moderate or severe disease was seen in 28 patients. The mean post-transplantation time at diagnosis was similar in patients with mild or moderate-severe renal involvement (1.05 and 1.3 years, respectively). All patients presented with similarly increased values of serum creatinine (mean 1.35 mg/dL). There was strong correlation between the number of PV infected cells in urine and the concurrent biopsies (p = 0.0001). In 13 patients PV was found only in urine; of these, two developed PVDz later. The positive predictive value of a positive urine was 90%, the negative predictive value of a negative urine was 99% and the accuracy of the test was 97%. We conclude that urine cytology is useful to evaluate renal transplant patients with PV reactivation because sloughed tubular cells are found in urine and positive urine samples are a consistent manifestation of PV renal involvement.

The human polyomaviruses

“…Taken together, these observations argue in favor of a caveolae-mediated endocytosis as the major route for BKV infectious entry [71]. In-support of the experimental evidence, ultrastructural analysis of BKV-infected renal tissue revealed that BK virions were localized to smooth, flask-shaped invaginations of the plasma membrane, which correspond to caveolae [72,73]. Conversely, JCV enters the target cell rapidly and requires proper assembly of clathrin-coated pits.…”

“…Viruses take advantage of the endocytic machinery to gain access to the cytosol and/or the nucleus of the target cell, where their replication and multiplication take place. BKV and JCV employ different internalization mechanisms to enter the host cell [69][70][71][72]. Dissection of the early events in the BKV lifecycle revealed that the virus enters cells by caveolae-mediated endocytosis.…”

Immunologic Control for Polyomavirus Infection after Kidney Transplantation

“…Urine cytology is inexpensive and simple, but its shortcoming is a high false-positive rate. However, according to the literature, the false-positive rate and positive predictive value of urine cytology are reported differently [2, 3], and these differences probably result from the rigorous protocols for early detection of PVN. It has been reported that urine PV proliferation (PV viruria) appears 4 weeks to several months prior to viremia [4, 5] and appears 12 weeks earlier than PVN [3, 6].…”

BK virus subtype IV nephropathy occurring 5 years after kidney transplantation

“…2A). A retrospective immunohistological stain with anti-BK virus antibody (a mouse monoclonal anti-BK virus large T antigen antibody; Cemicon) showed some positive nuclei in the tubular epithelium, while there was a lack of virally induced epithelial cell lysis, presenting as typical stage A according to Drackenberg's classifi cation 5 (Fig. 2B).…”