| Abstrakt: |
Reactivation of BKvirus in renal allografts causes a destructive chronic infection. This single‐center retrospective cohort study describes the evolution of BKvirus 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/TAin 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% CI2.19–11.396, p < 0.001), deceased donor (HR3.201, 95% CI1.149–8.915, p = 0.026), and late acute rejection (HR3.124, 95% CI1.037–9.413, p = 0.043). Transplant failure occurred in 38.1%, with uncontrolled infection (58.3%) and SV40T‐negative chronic rejection (41.7%) causing losses. BKVANis characterized by subacute virus‐induced tubular injury, inflammation, and progressive nephron destruction. Effective antiviral therapy remains an unmet clinical need. This longitudinal cohort study uses sequential histopathology to detail the relationships and kinetics of viral cytopathic effect, interstitial inflammation, and progressive nephron destruction occurring in transplanted kidneys infected with BK virus. See the companion article from Drachenberg et al on page 2078, and Mengel's editorial on page 1972. |
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