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BK polyomavirus-associated nephropathy

What's new

Added 2024 TTS and 2019 AST guidelines for the diagnosis and management of BK polyomavirus-associated nephropathy.

Background

Overview

Definition
BKPyV-nephropathy is a kidney disease caused by the BKPyV, which generally results in asymptomatic infections but can cause severe complications in immunocompromised patients, especially kidney transplant recipients.
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Pathophysiology
The pathophysiology of BKPyV-nephropathy involves the reactivation of BKPyV in renal tubular cells and the uroepithelium, leading to viral replication and immune-mediated tissue damage. BKPyV-encoded microRNAs have been shown to control viral replication and assist in immune evasion.
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Epidemiology
BKPyV viremia and BKPyV-nephropathy are reported to affect 10-20% and 1-10% of kidney transplant recipients, respectively.
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Risk factors
Risk factors for BKPyV-nephropathy include intense immunosuppression, HLA mismatches, prior rejection and anti-rejection treatment, and BKPyV-seropositive donor/seronegative recipient pairs.
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Disease course
The clinical course of BKPyV-nephropathy is characterized by the progression from asymptomatic BKPyV reactivation to overt nephropathy, most commonly 2-6 months after transplantation.
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Prognosis and risk of recurrence
The prognosis of BKPyV-nephropathy is generally poor, with graft loss occurring in > 50% of cases. However, early detection and reduction of immunosuppression can significantly improve outcomes, reducing graft loss to < 10% of cases.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of BK polyomavirus-associated nephropathy are prepared by our editorial team based on guidelines from the Transplantation Society (TTS 2024), the American Society of Transplantation (AST 2019), and the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2009).
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Screening and diagnosis

Pre-transplant testing
As per AST 2019 guidelines:
Do not obtain testing for genetic markers, BKPyV viruria, virus genotyping, or BKPyV virus-like particles/VP1-specific-specific antibody levels in kidney transplant donors before transplantation.
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Do not obtain testing for genetic markers, BKPyV virus-like particles/Vp1-specific antibody levels, or BKPyV (subtype)-neutralizing antibody levels, or BKPyV‐specific T‐cell quantity or function in kidney recipients before kidney transplantation.
D
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  • Indications for screening (kidney transplant recipients)

  • Indications for screening (non-kidney transplant recipients)

Diagnostic investigations

NAATs: as per TTS 2024 guidelines, use quantitative nucleic acid testing assays targeting conserved BKPyV genome sequences to allow the detection of all genotypes and variants.
B
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  • Donor-specific antibodies

  • Evaluation for JC polyomavirus‐associated nephropathy

Diagnostic procedures

Renal biopsy: as per TTS 2024 guidelines, perform kidney biopsy as clinically indicated (such as increased serum creatinine, proteinuria, hematuria) in patients with detectable BKPyV-DNAemia.
A
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  • Histopathology

Medical management

Reduction of immunosuppression, general principles: as per TTS 2024 guidelines, consider confirming that all immunosuppressive drug doses and concentrations are within the institutional target range.
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  • Reduction of immunosuppression (antimetabolite first)

  • Reduction of immunosuppression (calcineurin inhibitor first)

  • Reduction of immunosuppression (mTOR inhibitors)

  • Reduction of immunosuppression (belatacept)

  • Adjunctive therapies

  • Management of acute rejection

Surgical interventions

Retransplantation: as per TTS 2024 guidelines, perform retransplantation in otherwise eligible patients who have lost their previous allograft due to BKPyV-nephropathy.
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Specific circumstances

Pediatric patients: as per TTS 2024 guidelines, obtain monthly screening for plasma BKPyV-DNAemia in pediatric kidney transplant recipients until 9 months post-transplantation, then every 3 months until 24 months post-transplantation.
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consider continuing screening every 3 months until 36 months post-transplantation.
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Follow-up and surveillance

Laboratory monitoring: as per TTS 2024 guidelines, monitor BKPyV-DNAemia every 2-4 weeks until clearance
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or stabilizing at plasma viral loads < 1,000 copies/mL.
B
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