Native Versus Allograft BK Polyomavirus Nephropathy: A Matched Cohort Study of Clinicopathological Features and Outcomes.

BACKGROUND: BK polyomavirus nephropathy (BKPyVN) is a well-recognized cause of graft dysfunction and loss in kidney transplant recipients (KTRs). However, its clinical and pathological features in the native kidneys of non- KTRs remain poorly defined. We aimed to characterize native-kidney BKPyVN and compare it with allograft BKPyVN. METHODS: We retrospectively analyzed the clinical, virological, pathological and prognostic features of native-kidney BKPyVN. A 1:4 matched cohort of KTRs with allograft BKPyVN served as the control group. Diagnosis was established by kidney biopsy with SV40-T immunohistochemical confirmation and supported by BKPyV DNA detection in urine and/or plasma. RESULTS: Nine patients with native-kidney BKPyVN were identified, including 6 who had undergone hematopoietic stem cell transplantation, 2 lung and 1 heart-lung transplantation. All underwent kidney biopsy for progressive kidney dysfunction. At diagnosis, all had marked BKPyV DNAviruria, and plasma BKPyV DNA was detectable in 8 of 9 patients. Tubular basement membrane (TBM) C4d staining was observed in 8 of 9 cases and correlated with the extent of tubular SV40-T positivity. Compared with allograft BKPyVN, native-kidney BKPyVN presented with higher plasma BKPyV DNA levels, greater intrarenal viral load and more severe tubulointerstitial injury (all p < 0.05). Kaplan-Meier analysis showed lower 12-month ESRD-free survival in patients with native-kidney BKPyVN than in those with allograft BKPyVN (p = 0.001). CONCLUSIONS: Native-kidney BKPyVN is associated with advanced tubulointerstitial injury, frequent TBM C4d deposition and poor short-term renal outcomes. The greater severity than allograft BKPyVN may largely reflect delayed diagnosis in the absence of routine BKPyV surveillance. Earlier BKPyV testing and timely kidney biopsy should be considered in high-risk patients with otherwise unexplained kidney dysfunction.