Histological Evolution of BK Virus–Associated Nephropathy: Importance of Integrating Clinical and Pathological Findings

Abstract

Long-term clinicopathological studies of BK-associated nephropathy (PyVAN) are not available. We studied 206 biopsies (71 patients), followed 3.09 ± 1.46 years after immunosuppression reduction. The biopsy features (% immunostain for PyV large T ag + staining and inflammation ± acute rejection) were correlated with viral load dynamics and serum creatinine to define the clinicopathological status (PyVCPS). Incidence of acute rejection was 28% in the second biopsy and 50% subsequently (25% mixed T cell-mediated allograft rejection (TCMR) + antibody-mediated allograft rejection (AMR); rejection overall affected 38% of patients (>50% AMR). Graft loss was 15.4% (0.8-5.3 years after PyVAN); 76% had complete viral clearance (mean 28 weeks). The only predictors of graft loss were acute rejection (TCMR p = 0.008, any type p = 0.07), and increased "t" and "ci" in the second biopsy (p = 0.006 and 0.048). Higher peak viremia correlated with poorer viral clearance (p = 0.002). Presumptive and proven PyVAN had similar presentation, evolution, and outcome. Late PyVAN (>2 years, 9.8%) justifies BK viremia evaluation at any point with graft dysfunction and/or biopsy evaluation. This study describes the histological evolution of PyVAN and corresponding clinicopathological correlations. Although the pathological features overall reflect the viral and immunological interactions, the PyVAN course remains difficult to predict based on any single feature. Appropriate clinical management requires repeat biopsies and determination of the PyVCPS at relevant time points, for corresponding personalized immunosuppression adjustment.

Treatment for presumed BK polyomavirus nephropathy and risk of urinary tract cancers among kidney transplant recipients in the United States

“…Viruria sometimes progresses to viremia (usually after a gap of a few weeks), with a reported incidence of 5–15%. Although the progress to viremia closely mirrors the onset of BKVN, the incidence of biopsy-proven BKVN is reported to be only 1–5%, likely due to the focal nature of BKV disease (9–11). BKVN often leads to renal allograft loss, and a substantial body of literature exists about this association and its management (8, 12).…”

Clinical characteristics and outcomes of late‐onset BK virus nephropathy in kidney and kidney‐pancreas transplant recipients

“…In our cohort 18% of kidney transplant recipients were diagnosed with BKPyVAN beyond 1 year post‐transplant; however, since the majority of our cohort was not routinely screened beyond 1 year post‐transplant, this represents a minimum estimate of the frequency of late‐onset BKPyVAN. These findings emphasize the importance of evaluating for BKPyV viremia at all times that a renal graft biopsy is deemed clinically necessary, as is recommended in current guidelines . Notably, the incidence rate of BKPyVAN was similar between SPK recipients and KTR, but SPK recipients were significantly more likely to develop late‐onset BKPyVAN, suggesting that monitoring in SPK recipients should be extended beyond 1 year for this group to optimize the opportunity for earlier detection and intervention.…”

“…Presumptive BKPyVAN was defined as a plasma BKPyV load >10 000 BKPyV DNA copies/mL, a well‐validated, sensitive, and specific threshold for biopsy‐proven BKPyVAN, as previously described . Proven and presumed cases were pooled for analysis to reflect the entire spectrum of clinical BKPyVAN, to include true cases of BKPyVAN that might have been missed because of a falsely negative biopsy, and because these clinical entities have been shown to have a generally similar histologic and clinical course . To verify comparability in BK viral load across assays, the clinically used BKPyV assay in this study was directly compared to the assay used to define the 10 000 BKPyV DNA copies/mL threshold for BKPyVAN, and demonstrated viral load results within 0.1 log BKPyV DNA copies/mL.…”

“…This definition of “late‐onset” is problematic both because the mean/median onset of BKPyVAN is often later than 6 months and because all major guidelines recommend routine BKPyV screening up to 1 year post‐transplant. Recent studies have documented the histological evolution of BKPyVAN and have noted isolated late cases occurring >2 years post‐transplantation . Additional data on BKPyVAN occurring beyond 1 year post‐transplant are necessary to identify the incidence and outcomes and to identify potential patient groups in whom longer durations of screening beyond 1 year post‐transplant might be appropriate.…”

BK Virus Nephropathy Revisited

“…The authors were well positioned to independently revisit the natural histologic and clinical evolution of BKVN under contemporary clinical screening protocols, maintenance immunosuppression, and immunosuppression reduction approaches in cases with viremia and BKVN (2,3). Both articles study kidney transplants with BKVN.…”