High Incidence and Early Onset of Urinary Tract Cancers in Patients with BK Polyomavirus Associated Nephropathy

Li, Yi-Jung; Wu, Hsin-Hsu; Chen, Cheng‐Hsu; Wang, Hsu-Han; Chiang, Yang‐Jen; Hsu, Hsiang-Hao; Pang, See‐Tong; Wang, Chia Hui; Tian, Ya-Chung

doi:10.3390/v13030476

Cited by 6 publications

(6 citation statements)

References 47 publications

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“…Once reactivated, BKPyV rapidly replicates, leading to viruria, viremia and even BKPyVN. Recently, BKPyV has even been considered as an oncogenic virus [ 4 , 5 ]. Because effective anti-BKPyV therapy is not yet available, immunosuppressant reduction is the mainstay of treatment but increases the risk of rejection of the graft.…”

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor-alpha blockade suppresses BK polyomavirus replication

Wang

et al. 2022

Infection

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Purpose BK Polyomavirus (BKPyV) infection manifests as renal inflammation and can cause kidney damage. Tumor necrosis factor-α (TNF-α) is increased in renal inflammation and injury. The aim of this study was to investigate the effect of TNF-α blockade on BKPyV infection. Methods Urine specimens from 22 patients with BKPyV-associated nephropathy (BKPyVN) and 35 non-BKPyVN kidney transplant recipients were analyzed. Results We demonstrated increased urinary levels of TNF-α and its receptors, TNFR1 and TNFR2, in BKPyVN patients. Treating BKPyV-infected human proximal tubular cells (HRPTECs) with TNF-α stimulated the expression of large T antigen and viral capsid protein-1 mRNA and proteins and BKPyV promoter activity. Knockdown of TNFR1 or TNFR2 expression caused a reduction in TNF-α-stimulated viral replication. NF-κB activation induced by overexpression of constitutively active IKK2 significantly increased viral replication and the activity of the BKPyV promoter containing an NF-κB binding site. The addition of a NF-κB inhibitor on BKPyV-infected cells suppressed viral replication. Blockade of TNF-α functionality by etanercept reduced BKPyV-stimulated expression of TNF-α, interleukin-1β (IL-1β), IL-6 and IL-8 and suppressed TNF-α-stimulated viral replication. In cultured HRPTECs and THP-1 cells, BKPyV infection led to increased expression of TNF-α, interleukin-1 β (IL-1β), IL-6 and TNFR1 and TNFR2 but the stimulated magnitude was far less than that induced by poly(I:C). This may suggest that BKPyV-mediated autocrine effect is not a major source of TNFα. Conclusion TNF-α stimulates BKPyV replication and inhibition of its signal cascade or functionality attenuates its stimulatory effect. Our study provides a therapeutic anti-BKPyV target.

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Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor-alpha blockade suppresses BK polyomavirus replication

Wang

et al. 2022

Infection

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“…27 While BK virus nephropathy has been associated with an increased incidence of GU malignancies, we did not observe GU malignancies in patients with BK viremia in our cohort. 28 In addition to GU malignancies, we observed other second malignancies in our cohort. One patient was diagnosed with systemic lightchain amyloidosis 4 years after transplantation which was not present on the patient's initial workup for multiple myeloma and one patient was diagnosed with lung adenocarcinoma.…”

Section: Myeloma and Second Malignanciesmentioning

confidence: 53%

Outcomes of kidney transplant recipients with ESKD due to plasma cell dyscrasia: A case series

Dinh

Wong

Martin

et al. 2021

Clinical Transplantation

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Transplant centers have historically been reluctant to proceed with kidney transplantation in individuals with plasma cell dyscrasias (PCDs) due to concern for high rates of PCD recurrence and PCD-related mortality. As novel therapies for PCDs have improved hematologic outcomes, strategies to optimize kidney transplantation in individuals with PCD-mediated kidney disease are needed. In this single-center case series we discuss our protocol for the transplantation of individuals with ESKD attributed to PCD as well as the hematologic and allograft outcomes of 12 kidney transplant recipients with ESKD attributed to PCD. Median follow-up time after kidney transplantation was 44 months (IQR 36, 84). All patients had a functioning allograft 1 year after kidney transplantation. 9/12 patients were alive and had a functioning allograft 5 years after kidney transplantation. Five patients experienced relapse of PCD (of whom three responded well to subsequent therapies) and four patients developed secondary malignancies, including three patients with urologic malignancies. This case series demonstrates that patients with kidney disease attributed to PCD have favorable outcomes with kidney transplantation. Transplant evaluation in patients with PCDs should involve a multidisciplinary team of transplant nephrologists and oncologists to select appropriate candidates. Providers should consider screening for urologic malignancies pre-and post-transplantation.

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“…21 Uncontrolled BKPyV replication in kidney recipients is a risk factor for BKPyV nephropathy (a common cause of graft loss), which is associated with elevated bladder cancer risk. 22,23 BKPyV can also cause hemorrhagic cystitis in stem cell transplant recipients. 6 BKPyV nephropathy is not known to occur among PLWH, and hemorrhagic cystitis has only rarely been reported.…”

Section: Discussionmentioning

confidence: 99%

Brief Report: The Virome of Bladder Tumors Arising in People Living With HIV

Starrett,

Foster,

Sigel

et al. 2023

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: People living with HIV (PLWH) have elevated risk for developing virus-related cancers. Bladder cancer risk is not increased in PLWH but is elevated among immunosuppressed solid organ transplant recipients (SOTRs). BK polyomavirus and, to a lesser extent, other viruses have been detected in bladder cancers from SOTRs. Objective: To characterize the virome of bladder tumors in PLWH. Design: Retrospective case series. Methods: We sequenced DNA and RNA from archived formalin-fixed bladder tumors from PLWH. Nonhuman reads were assembled and matched to a database of known viruses. Results: Fifteen bladder tumors from PLWH (13 carcinomas, 2 benign tumors) were evaluated. Fourteen tumors were in men, and the median age at diagnosis was 59 years (median CD4 count 460 cells/mm3). All but 1 tumor yielded both sufficient DNA and RNA. One bladder cancer, arising in a 52-year-old man with a CD4 count of 271 cells/mm3, manifested diverse Alphatorquevirus DNA and RNA sequences. A second cancer arising in a 58-year-old male former smoker (CD4 count of 227 cells/mm3) also showed Alphatorquevirus and Gammatorquevirus DNA sequences. Neither tumor exhibited viral integration. Conclusions: Alphatorqueviruses and Gammatorqueviruses are anelloviruses, which have also been detected in bladder cancers from SOTRs, but anelloviruses are common infections, and detection may simply reflect increased abundance in the setting of immunosuppression. The lack of detection of BK polyomavirus among bladder tumors from PLWH parallels the lower level of bladder cancer risk seen in PLWH compared with SOTRs, indirectly supporting a role for BK polyomavirus in causing the excess risk in SOTRs.

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High Incidence and Early Onset of Urinary Tract Cancers in Patients with BK Polyomavirus Associated Nephropathy

Cited by 6 publications

References 47 publications

Tumor necrosis factor-alpha blockade suppresses BK polyomavirus replication

Tumor necrosis factor-alpha blockade suppresses BK polyomavirus replication

Outcomes of kidney transplant recipients with ESKD due to plasma cell dyscrasia: A case series

Brief Report: The Virome of Bladder Tumors Arising in People Living With HIV

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