Virology & risk factors
Virus
- BK is a polyomavirus (family Polyomaviridae); related JC and SV40
- Primary infection in childhood; latent in urothelium and renal tubular cells
- Reactivation under immunosuppression — peaks 2–12 months post-transplant
Risk Factors
- Tacrolimus (more than ciclosporin)
- Triple immunosuppression with MMF
- Steroid-resistant rejection treated with thymoglobulin or high-dose steroids
- HLA mismatch, deceased donor, older donor
- Recipient seronegativity, donor seropositivity
- Ureteric stent in situ > 6 weeks
- Diabetes, male sex
Screening, diagnosis & differential
SCREENING (UK protocol):
- Plasma BK PCR monthly for first 6 months
- Every 3 months until 12 months
- Whenever serum creatinine rises unexplained, or before rejection treatment
Interpretation
- Negative or < 1,000 copies/mL — no action; rescreen as scheduled
- 1,000–10,000 copies/mL — increase monitoring; review immunosuppression
- > 10,000 copies/mL (4 log) — 'presumed BKVN' — act now
- > 100,000 copies/mL (5 log) — high probability of biopsy-proven BKVN
Biopsy
- Indicated for sustained high-level viraemia (> 10,000) or unexplained creatinine rise
- Histology: tubular cells with intranuclear basophilic inclusions; tubulitis; interstitial inflammation
- SV40 large-T antigen immunostain confirms BK (or JC, much rarer)
- Banff scheme for PVN — pvl1 (minimal) to pvl3 (extensive)
- Concurrent acute T-cell mediated rejection in 10–30% — challenging to manage
Urine Tests
- Decoy cells on urine cytology — sensitive but non-specific
- Urine BK PCR — universally positive in BKVN but also in many recipients without disease — not used for diagnosis
Differential
- Acute T-cell or antibody-mediated rejection
- Calcineurin inhibitor toxicity
- Pyelonephritis
- Recurrent or de novo glomerular disease
- Drug-induced interstitial nephritis
Management & prevention
FIRST-LINE — REDUCE IMMUNOSUPPRESSION (stepwise):
- Reduce tacrolimus trough to 4–6 ng/mL
- Halve MMF dose; if no response, stop MMF
- If still viraemic, switch MMF to mTOR inhibitor (sirolimus / everolimus, trough 4–8)
- Reduce prednisolone to maintenance 5 mg if higher
- Monitor plasma BK PCR every 2 weeks until clearance (≥ 2 negatives)
- Monitor creatinine weekly during de-escalation
ADJUNCTIVE (limited evidence — consider in refractory / progressive cases):
- IVIg 0.5–2 g/kg — especially helpful when reducing IS risks rejection
- Leflunomide 100 mg loading × 3 days then 20–40 mg daily; monitor LFTs; long half-life
- Ciprofloxacin 500 mg BD for 1–3 months — modest in vitro activity
- Cidofovir 0.25–1 mg/kg/week without probenecid — nephrotoxic, rarely used
- Brincidofovir — in clinical trials
- Allogeneic BK-specific T cells — experimental, available in specialist centres
Managing Concurrent Rejection
- If biopsy shows BKVN + rejection — treat rejection first (pulse steroids), then immediately reduce baseline IS once rejection settles
- Avoid lymphocyte-depleting therapy unless severe rejection
Follow-up After Clearance
- Continue monthly plasma BK PCR for 6 months after clearance
- Slowly re-introduce MMF if no recurrence
- Long-term graft surveillance — risk of late chronic allograft injury
Graft Loss
- Return to dialysis if graft fails
- Failed graft nephrectomy considered if persistent viraemia/inflammation
- Re-transplantation possible once BK PCR negative — most centres want ≥ 2 negative plasma PCRs and a recovery period
Prevention
- Tailor induction immunosuppression — avoid over-suppression
- Minimise steroid pulses
- Remove ureteric stents promptly
- Adherence to screening protocol is the single most impactful intervention
