A Novel Treatment Regimen for BK Viremia

Zaman, Rumina A.; Ettenger, Robert B.; Cheam, Hay; Malekzadeh, Mohammed H.; Tsai, Ethan

doi:10.1097/01.tp.0000441825.72639.4f

Cited by 40 publications

(30 citation statements)

References 32 publications

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“…Other alternative therapies include leflunomide and fluoroquinolone antibiotics [12]; however, experience is limited, even in adults [13]. Few reports of leflunomide use in the setting of HSCT are available and its safety has not been Figure 1.…”

Section: Discussionmentioning

confidence: 99%

“…The current first line BKV-oriented therapy is intravenous cidofovir; however, its efficacy remains controversial [2]. Alternative strategies include intravesical instillation of cidofovir [2,7], hyperbaric oxygen therapy [11], leflunomide, and fluoroquinolone [12]; however, their effect is limited [13]. Invasive intervention such as vascular embolization or cystectomy may be necessary in uncontrollable HC.…”

Section: Introductionmentioning

confidence: 98%

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Choreito Formula for BK Virus–associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Kawashima

Ito

Sekiya

et al. 2015

Biology of Blood and Marrow Transplantation

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Therapy for BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is limited after hematopoietic stem cell transplantation (HSCT). We examined whether choreito, a formula from Japanese traditional Kampo medicine, is effective for treating BKV-HC. Among children who underwent allogeneic HSCT between October 2006 and March 2014, 14 were diagnosed with BKV-HC (median, 36 days; range, 14 to 330 days) after HSCT, and 6 consecutive children received pharmaceutical-grade choreito extract granules. The hematuria grade before treatment was significantly higher in the choreito group than in the nonchoreito group (P = .018). The duration from therapy to complete resolution was significantly shorter in the choreito group (median, 9 days; range, 4 to 17 days) than in the nonchoreito group (median, 17 days; range, 15 to 66 days; P = .037). In 11 children with macroscopic hematuria, the duration from treatment to resolution of macroscopic hematuria was significantly shorter in the choreito group than in the nonchoreito group (median, 2 days versus 11 days; P = .0043). The BKV load in urine was significantly decreased 1 month after choreito administration. No adverse effects related to choreito administration were observed. Choreito may be a safe and considerably promising therapy for the hemostasis of BKV-HC after HSCT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Choreito Formula for BK Virus–associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Kawashima

Ito

Sekiya

et al. 2015

Biology of Blood and Marrow Transplantation

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“…Because of the difficulty in predicting BKVN in transplant recipients, a latent period from BK viraemia to the development of BKVN, and possible sampling errors in diagnosing early BKVN due to its focal nature[25], screening of the blood or urine for BKV infection and pre-emptive reduction of immunosuppressants when BKV is detected have been shown to reduce, the risk of the development of BKVN (0.8%-1.3%)[27,28,32,33]. Interestingly, some centres report that despite having a BKV screening programme in the literature, their incidence of BKVN is greater than that seen in our cohort (4.2%-6.4%)[11,26,31], This includes one centre that screened for decoys cells in urine fortnightly for the first 3 mo, then at 6 and 12 mo and yearly after transplant[31].…”

Section: Discussionmentioning

confidence: 99%

Outcomes of renal transplant recipients with BK virus infection and BK virus surveillance in the Auckland region from 2006 to 2012

Hsiao¹,

Pilmore²,

Zhou³

et al. 2016

WJN

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AIMTo evaluate incidence, risk factors and treatment outcome of BK polyomavirus nephropathy (BKVN) in a cohort of renal transplant recipients in the Auckland region without a formal BK polyomavirus (BKV) surveillance programme.METHODSA cohort of 226 patients who received their renal transplants from 2006 to 2012 was retrospectively reviewed.RESULTSSeventy-six recipients (33.6%) had a BK viral load (BKVL) test and 9 patients (3.9%) developed BKVN. Cold ischaemia time (HR = 1.18, 95%CI: 1.04-1.35) was found to be a risk factor for BKVN. Four recipients with BKVN had complete resolution of their BKV infection; 1 recipient had BKVL less than 625 copies/mL; 3 recipients had BKVL more than 1000 copies/mL and 1 had graft failure from BKVN. BKVN has a negative impact on graft function [median estimated glomerular filtration rate (eGFR) 22.5 (IQR 18.5-53.0) mL/min per 1.73 m2, P = 0.015), but no statistically significant difference (P = 0.374) in renal allograft function was found among negative BK viraemia group [median eGFR 60.0 (IQR 48.5-74.2) mL/min per 1.73 m2), positive BK viraemia without BKVN group [median eGFR 55.0 (IQR 47.0-76.0) mL/min per 1.73 m2] and unknown BKV status group [median eGFR 54.0 (IQR 43.8-71.0) mL/min per 1.73 m2]. The incidence and treatment outcomes of BKVN were similar to some centres with BKV surveillance programmes.CONCLUSIONRecipients with BVKN have poorer graft function. Although active surveillance for BKV has been shown to be effective in reducing incidence of BKVN, it should be tailored specifically to that transplant centre based on its epidemiology and outcomes of BKVN, particularly in centres with limited resources.

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“…Given that there has been some benefit with CDV, CPRO or LEF (42, 43), these agents were considered an important starting point for potential therapeutics targeting BKPyV associated HIV-SGD. HIV-SGD (29) is AIDS defining in pediatric HIV infection and increasing in the adult HIV population (44).…”

Section: Discussionmentioning

confidence: 99%

Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system

2015

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BK polyomavirus (BKPyV) is a known kidney tropic virus that has been detected at high levels in HIV-associated salivary gland disease (HIV-SGD), one of the most important AIDS associated oral lesions. BKPyV has been detected in HIV-SGD patient saliva and replicates in salivary gland cells in vitro. BKPyV antivirals are currently in wide use to guard against BKPyV mediated organ rejection in kidney transplant recipients. The goal of this study was to investigate the inhibitory effects of three such antiviral agents, ciprofloxacin, cidofovir, and leflunomide in BKPyV infected salivary gland cells. Human salivary gland cells, and Vero cells, were infected with BKPyV, treated with antiviral drugs and assessed for BKPyV gene expression and viral replication for up to 5 days post infection. The kinetics of BKPyV replication were different in salivary gland cells compared to kidney cells. Ciprofloxacin and cidofovir had minimal effect on metabolic activity and host cell DNA replication, however, cell toxicity was detected at the protein level with leflunomide treatment. Ciprofloxacin decreased BKV T Ag and VP1 mRNA expression by at least 50% in both cell types, and decreased T Ag protein expression at days 3 and 4 post infection. A 2.5 – 4 log decrease in intracellular DNA replication and a 2 – 3 log decrease in progeny release were detected with ciprofloxacin treatment. Cidofovir and leflunomide also inhibited BKPyV gene expression and DNA replication. The three drugs diminished progeny release by 30–90% and 2 – 6 fold decreases in infectious virus were detected post drug treatment by fluorescence focus assay. Additionally, three clinical BKPyV isolates were assessed for their responses to these agents in vitro. Cidofovir and leflunomide, but not ciprofloxacin treatment resulted in statistically significant inhibition of BKPyV progeny release from salivary gland cells infected with HIV-SGD BKPyV isolates. All three drugs decreased progeny release from cells infected with a transplant derived viral isolate. In conclusion, treatment of human salivary gland cells with each of the three drugs produced modest decreases in BKPyV genome replication. These data highlight the need for continued studies to discover more effective and less toxic drugs that inhibit BKPyV replication in salivary gland cells.

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A Novel Treatment Regimen for BK Viremia

Abstract: This analysis demonstrates for the first time that, used in a stepwise fashion, ciprofloxacin and leflunomide are effective and safe treatments for BK viremia in PRTR.

Cited by 40 publications

References 32 publications

Choreito Formula for BK Virus–associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Choreito Formula for BK Virus–associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Outcomes of renal transplant recipients with BK virus infection and BK virus surveillance in the Auckland region from 2006 to 2012

Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system

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