Clin Transplant Res.  2024 Jun;38(2):71-89. 10.4285/ctr.24.0006.

Polyomavirus nephropathy: diagnosis, histologic features, and differentiation from acute rejection

• Nast CC

• KMID: 2557601
• DOI: http://doi.org/10.4285/ctr.24.0006

Abstract

Polyomaviruses, particularly BK virus, are ubiquitous latent infections that may reactivate with immunosuppression during kidney transplantation, resulting in polyomavirus nephropathy (PVN). The levels of viruria and viremia serve as tools for screening and making a presumptive diagnosis of PVN, respectively, while a definitive diagnosis requires a kidney biopsy. There are histologic classifications of PVN based on the extent of tubular cell viral infection, interstitial fibrosis, and interstitial inflammation. These classifications correlate to some degree with graft function and loss, aiding in determining treatment efficacy and prognostication. PVN has histologic overlap with acute cell-mediated rejection, making the differential diagnosis challenging, although there are suggestive features for these different causes of graft dysfunction. This article reviews the diagnosis, histologic findings, and classifications of PVN, and discusses how to differentiate viral nephropathy from acute rejection.

Keyword

Polyomavirus; BK virus; Viremia; Kidney biopsy; Graft rejection

Figure

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  Fig. 1 Tubular epithelial cell viral cytopathic features in BK virus nephropathy. (A) Ground glass amorphous (arrow) and finely granular (arrowhead) intranuclear inclusions (H&E, ×600). (B) Vesicular intranuclear (arrows) and eosinophilic (arrowhead) intranuclear inclusions (H&E, ×600). (C) Eosinophilic dense granular intranuclear inclusions with circumferential halos (arrows) and necrotic desquamated virally infected tubular cells (arrowheads; Jones methenamine silver, ×600). (D) Different viral cytopathic features (arrows) in one biopsy (PAS, ×400).

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  Fig. 2 Electron microscopy of a tubular cell infected with BK virus. (A) Extensive intranuclear viral particles (virions) showing loose aggregation and paracrystalline arrays (arrows; ×12,000). (B) Virions clumped loosely and in arrays (×19,000). (C) Virions at higher magnification (×48,000).

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  Fig. 3 Morphologic features of BK virus nephropathy. (A) Sharply demarcated geographic inflammation associated with focally infected tubular cells (arrows; Jones methenamine silver, ×40). (B) Prominent medullary viral infection and inflammation with no cortical involvement. Note the arcuate artery (arrow) between the medulla to the right of the artery and cortex to the left of the artery (Jones methenamine silver, ×100). (C) Plasma cell-rich mixed inflammation in areas of viral infection (Jones methenamine silver, ×400). (D) Focal macrophage aggregation (arrow) around an injured tubule (PAS, ×600).

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  Fig. 4 Immunohistochemistry for simian virus 40 large T antigen. (A) Extensive dark brown staining of predominantly distal tubular epithelial cell nuclei (×200). (B) Staining of several tubular cell nuclei (arrows) within only one distal tubule (×400).

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  Fig. 5 Selected examples of the American Society of Transplantation Infectious Disease Community of Practice polyomavirus histologic classes. Class A: (A) <10% interstitial inflammation (ti0) and <10% tubulointerstitial scarring (interstitial fibrosis/tubular atrophy [IFTA] 0; PAS, ×100). (B) Minor interstitial inflammation with few infected tubular cells arrow; Jones methenamine silver, ×100). Class B2: (C) moderate interstitial inflammation (ti2) with moderate (26%–50%) parenchymal tubular cell cytopathic changes (arrows) in the medulla (Jones methenamine silver, ×100). (D) Moderate inflammation (arrows) and mild tubular atrophy with interstitial fibrosis (IFTA 1) in the cortex (arrowheads; Jones methenamine silver, ×100). Class B3: (E) interstitial inflammation involves 80% of the cortex (ti3; Jones methenamine silver, ×100). (F) Moderate (>25%–50%) interstitial fibrosis and tubular atrophy (IFTA 2; arrowheads) with tubular cell viral cytopathic changes in >50% of the parenchyma (Jones methenamine silver, ×200). (G) Higher magnification showing marked tubular cell cytopathic features (arrows; H&E, ×400).

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  Fig. 6 Examples of the Banff polyomavirus histologic classes. Class 1: (A) Simian virus 40 (SV40) staining (arrows) in <1% of the tubules (polyomavirus load [pvl] 1; ×200). (B) There is minimal interstitial fibrosis (ci0) (Jones methenamine silver, ×100). Class 2: (C) There are 1%–10% tubules with cells staining for SV40 (pvl 2), although one tubule has many infected cells (arrow; ×400). (D) There is mild interstitial fibrosis (ci1) with inflammation (arrows; PAS, ×100). Class 2: (E) >10% of the tubules have infected epithelial cells (arrows; pvl 3; ×200). (F) Minor interstitial fibrosis (ci0; PAS, ×100). Class 3: (G) There is extensive (>10%) tubular infection with BK virus (pvl 3) shown by SV40 staining (×40). (H) Severe (>50%) interstitial fibrosis with inflammation (ci3; arrows; PAS, ×40).

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  Fig. 7 BK virus nephropathy before and after viral clearance. Time of BK virus nephropathy diagnosis with >2 million viral copies/mL plasma. (A) There is severe inflammation in the interstitium (i3) and in tubules (t3, arrow). Necrotic desquamated tubular cells with cytopathic changes are in several tubules (arrowheads; H&E, ×200). (B) Simian virus 40 (SV40) immunohistochemical stain showing extensive infection of tubular cells (arrowheads; ×200). Kidney biopsy was done 3.5 months later, following treatment with reduced immunosuppression, intravenous immunoglobulin G, and leflunomide, with 13 viral copies/mL plasma. (C) There is mild inflammation in the interstitium (i1) and in tubules (t1; arrows; PAS, ×200). (D) SV40 immunohistochemical stain shows no infected tubular cells (×200).

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  Fig. 8 Glomerular parietal epithelial cell infection with BK virus. (A) Parietal epithelial cells with cytopathic features (arrows; PAS, ×600). (B) Positive immunohistochemical stain for simian virus 40 in parietal (arrows) and tubular (arrowhead) epithelial cells (×600).

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