Pathological characteristics of BK polyomavirus-associated nephropathy with glomerular involvement

Background: This study aimed to investigate the pathological characteristics of BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) with glomerular involvement in kidney transplant recipients. Methods: Forty-four patients with glomerular BKPyV infection were retrospectively induded for analysis. Immunohistochemical (IHC) staining was performed on paraffin sections using monoclonal mouse antiSV40 large T antigen antibody. Results: In BKPyV-infected glomeruli, the glomerular parietal epithelial cells (GPECs) were swollen, hyperchromatic, and enlarged, with an increased nuclear to cytoplasm (N/C) ratio and smudgy basophilic intra-nuclear viral inclusions. IHC staining revealed the distribution of BKPyV involvement in GPECs, podocytes, and shedding cells within Bowman's space. Notably, BKPyV affected GPEC proliferation and caused crescent formation (7 biopsies, 15.9%). Three biopsies exhibited fibrous crescents and the absence of viral inclusions. The other 4 biopsies exhibited cellular and fibro-cellular crescents, with viral cytopathic changes and positive IHC staining in the proliferative GPECs. Electron microscopy showed viral particles in both GPECs and podocytes. BKPyV-infected GPECs were degenerative, with mitochondrial swelling, endoplasmic reticulum expansion, and multi-layered membranous structure formation. Twelve (27.3%) patients received repeat biopsies within 1.6 to 39.5 months (median: 13.5 months), but none revealed persistent glomerular BKPyV infection. Conclusions: Distinct glomerular changes in BKPyVAN biopsies should raise the possibility of glomerular involvement.