title: BK Virus Nephropathy: Histological Evolution by Sequential Pathology.
abstract: Reactivation of BK virus in renal allografts causes a destructive chronic infection. This single-center retrospective cohort study describes the evolution of BK virus allograft nephropathy (BKVAN) from 63 kidneys (from 61 patients) using sequential histopathology (454 biopsies, averaging 7.8 ± 2.6 per kidney) followed for 60.1 mo. Uninfected protocol biopsies formulated time-matched control Banff scores (n = 975). Interstitial inflammation occurred in 73% at diagnosis, correlating with viral histopathology (r = 0.413, p = 0.008) and amplifying early injury with accelerated interstitial fibrosis and tubular atrophy (IF/TA, p = 0.017) by 3 mo. Prodromal simian virus 40 large T antigen (SV40T)-negative inflammation with viremia preceded the histological diagnosis in 23.8%. Persistent subacute injury from viral cytopathic effect was associated with acute tubular necrosis and ongoing interstitial inflammation, culminating in IF/TA in 86.9%. Overall, cellular interstitial infiltration mitigated the intensity of subsequent tubular injury, SV40T, and tissue viral load, assessed by sequential paired histology (p < 0.001). Graft loss was predicted by high-level viremia (hazard ratio [HR] 4.996, 95% CI 2.19-11.396, p < 0.001), deceased donor (HR 3.201, 95% CI 1.149-8.915, p = 0.026), and late acute rejection (HR 3.124, 95% CI 1.037-9.413, p = 0.043). Transplant failure occurred in 38.1%, with uncontrolled infection (58.3%) and SV40T-negative chronic rejection (41.7%) causing losses. BKVAN is characterized by subacute virus-induced tubular injury, inflammation, and progressive nephron destruction. Effective antiviral therapy remains an unmet clinical need.
authors.affiliation: Department of Renal Medicine, Westmead Hospital, Westmead, Australia.
authors.forename: B J
authors.initials: BJ
authors.lastname: Nankivell
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, ICPMR, Sydney, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Renthawa
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, ICPMR, Sydney, Australia.
authors.forename: R N
authors.initials: RN
authors.lastname: Sharma
authors.affiliation: Department of Renal Medicine, Westmead Hospital, Westmead, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Kable
authors.affiliation: Department of Renal Medicine, Westmead Hospital, Westmead, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Connell
authors.affiliation: Department of Renal Medicine, Westmead Hospital, Westmead, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Chapman
mesh_terms: D001739:BK Virus / Q000302:isolation & purification / Q000472:pathogenicity; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000473:pathology*; D006085:Graft Survival; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000009:adverse effects*; D027601:Polyomavirus Infections / Q000209:etiology / Q000473:pathology*; D011183:Postoperative Complications; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D014412:Tumor Virus Infections / Q000209:etiology / Q000473:pathology*; D019562:Viral Load; D014766:Viremia / Q000209:etiology / Q000473:pathology*
keywords: clinical research/practice; complication: infectious; infection and infectious agents; infectious disease; kidney transplantation/nephrology; pathology/histopathology; viral: BK/JC/polyoma