Questions

BK virus — Questions

Study questions about BK virus — exam-style, clinical-scenario and FAQ.

Mock Exam mode

Sit this set one question at a time. Multiple-choice questions mark themselves; written questions reveal a tickable mark scheme so you can score your own answer. You get a combined score at the end.

11 questions: 7 MCQ, 4 written.

High-priority (past-paper) questions only

Why A

There is no antiviral of proven benefit, so the mainstay is stepwise reduction of immunosuppression, guided by the plasma viral load, to restore BK-virus-specific T-cell control; this clears the virus in about 80 per cent of patients. Aciclovir and ganciclovir have no useful activity against BK virus, a randomised trial of levofloxacin showed no effect, and increasing immunosuppression would worsen replication.

A complete answer separates the specimen used for decisions from the one used for screening, states the surveillance schedule, and makes management hinge on immunosuppression.

Specimens

The plasma BK virus DNA load is the decision marker: virus in the blood reflects significant renal replication and is what triggers and monitors treatment. Urinary shedding is near-universal in reactivation, so it is sensitive but not specific, and a high urine load alone does not establish nephropathy. Proven nephropathy requires a renal biopsy with viral cytopathic change and positive SV40 large T antigen immunohistochemistry, taking at least two cores including medulla because the disease is focal.

Screening schedule

All kidney transplant recipients are screened for plasma BK virus DNA at intervals: conventionally monthly until about nine months after transplant, then every three months until two years. A sustained plasma load above 10,000 copies per millilitre is taken as presumptive nephropathy and prompts intervention before the graft is damaged.

Management

The mainstay is stepwise reduction of immunosuppression to restore BK-virus-specific T-cell control: reduce the antimetabolite to no more than half its dose and lower the calcineurin-inhibitor target, which clears the virus in around 80 per cent of patients. There is no antiviral of proven benefit, and adjuncts are reserved for failure of reduction. The important caveat is concurrent acute rejection: if rejection coexists, it is treated first and immunosuppression reduced only afterwards, because the two conditions demand opposite changes.

Features

BK-virus haemorrhagic cystitis is high-level replication of BK virus in the urothelium, causing denudation and bleeding of the bladder lining. It is of late onset, some two to twelve weeks after engraftment, and is defined by the combination of cystitis symptoms (dysuria, frequency, suprapubic pain), visible haematuria with clots, and a high urine BK virus load. Two transplant-specific factors amplify it: prior urotoxic conditioning, in which cyclophosphamide and its metabolite acrolein damage the bladder epithelium, and the inflammatory surge of immune reconstitution at engraftment.

Distinction from early cystitis

Early haemorrhagic cystitis, occurring in the first days after transplant, is due to conditioning toxicity alone and is brief; it is not caused by BK virus. The later onset, the high urine BK load and the timing around engraftment separate BK-virus cystitis from this earlier urotoxic form.

Management

Management is largely supportive: hydration, bladder irrigation, evacuation of clots, and transfusion of platelets or red cells as needed, while returning cellular immunity brings the infection under control. There is no antiviral of proven benefit. Reducing immunosuppression, the mainstay in renal nephropathy, is constrained here by the risk of graft-versus-host disease.

Why it matters

The two conditions look alike but demand opposite treatment. Both present as graft dysfunction with a rising creatinine and both show an interstitial inflammatory infiltrate with tubulitis on biopsy, yet nephropathy is treated by reducing immunosuppression while rejection is treated by augmenting it. Choosing wrongly harms the graft: cutting immunosuppression in rejection accelerates it, and increasing it in nephropathy fuels viral replication.

How they are distinguished

A high and rising plasma BK virus load points to nephropathy, which is then confirmed on biopsy by viral cytopathic change with positive SV40 large T antigen immunohistochemistry. Acute rejection is favoured by features such as endarteritis and, in antibody-mediated rejection, C4d deposition along peritubular capillaries, in the absence of viral staining. The two can coexist, and biopsy with the SV40 stain is what separates them. When both are present, rejection is treated first and immunosuppression reduced only afterwards.

Pathogenesis

BK virus persists for life in the renal tubular epithelium and urothelium and is held in check by cellular immunity. After kidney transplantation the immunosuppression needed to protect the graft permits uncontrolled lytic replication, and the replicating virus is frequently donor-derived, carried in with the kidney. Infected tubular cells enlarge with intranuclear inclusions, round up and slough into the urine as decoy cells, and lyse, releasing virus and provoking an interstitial inflammatory infiltrate. The process is graded through three histological stages, from early cytopathic change with little inflammation, through interstitial inflammation and tubulitis, to tubular atrophy and fibrosis, the last representing irreversible scarring and graft loss.

Specimens for screening versus diagnosis

Screening uses the plasma BK virus DNA load, which reflects renal replication and is the marker that triggers pre-emptive treatment; urine load and decoy cells are more sensitive but less specific, useful as a first filter rather than a decision point. Diagnosis of proven nephropathy is histological: a renal biopsy showing viral cytopathic change with an inflammatory infiltrate, confirmed by SV40 large T antigen immunohistochemistry. Because the infection is focal and favours the medulla, at least two cores including medulla are taken, and a negative stain does not exclude early disease.

Why E

BK virus attaches to branched gangliosides (GT1b and GD1b) displayed on renal tubular epithelium and urothelium and enters by caveolin-dependent endocytosis, which directs it to the urinary tract. JC virus, by contrast, uses a sialylated glycan with the serotonin 5-HT2A receptor and a clathrin route into glial cells, which is why it targets the brain. The other options describe unrelated viruses.

Why B

Decoy cells are infected tubular and urothelial cells bearing ground-glass intranuclear inclusions, shed into the urine during BK-virus reactivation; they are a sensitive but non-specific marker of replication. They are not malignant cells, are distinct from the owl-eye cells of cytomegalovirus, and have nothing to do with eosinophils or red-cell casts.

Two cystitis patterns after stem-cell transplant

Early (first days, around conditioning): chemical cystitis caused directly by urotoxic conditioning agents (cyclophosphamide, ifosfamide, busulfan).
Late (after engraftment, typically weeks 3 to 6): BK polyomavirus haemorrhagic cystitis, with a high urinary BK load, as in this case.

The timing separates the two, which is why option B (placing chemical cystitis weeks after engraftment) is wrong.

Diagnosis and management

BK haemorrhagic cystitis is a bladder disease, not the renal-allograft nephropathy (option C), and the urinary load alone does not equate to disease: 50 to 80 per cent of stem-cell recipients have high viruria but fewer than 20 per cent develop cystitis, so viruria is necessary but not sufficient (option E is wrong). Management is largely supportive: hydration, bladder irrigation, analgesia and transfusion as needed; no antiviral is of proven benefit, though cidofovir is sometimes tried. Option D is wrong because this is BK, not CMV, disease.

Why D

The plasma BK virus DNA load is the decision marker, because virus in the blood reflects significant renal replication; a sustained plasma load above 10,000 copies per millilitre is taken as presumptive nephropathy and prompts pre-emptive reduction of immunosuppression. Urinary shedding and decoy cells are sensitive but not specific, serology does not guide treatment, and a creatinine rise alone is non-specific.

Why C

Proven nephropathy requires viral cytopathic change with positive immunohistochemistry for the SV40 large T antigen, using an antibody that cross-reacts with the BK-virus large T antigen to stain infected tubular nuclei. C4d marks antibody-mediated rejection, not BK disease; Congo red, silver and cytomegalovirus stains identify unrelated processes.

Why B

No antiviral has proven benefit against BK virus, and management rests on reducing immunosuppression. A randomised trial of levofloxacin showed no effect on viral load; cidofovir gives inconsistent results and carries nephrotoxicity and uveitis; and ganciclovir and aciclovir have no useful activity against BK virus.

High priorityMCQ
The primary management of BK-virus-associated nephropathy in a kidney transplant recipient is to:
- A. Reduce immunosuppression under viral-load guidance
- B. Start high-dose intravenous aciclovir
- C. Add a fluoroquinolone such as oral levofloxacin for three months
- D. Increase immunosuppression to suppress the virus
- E. Begin intravenous ganciclovir
Show answer
Correct answer: A
Why A

There is no antiviral of proven benefit, so the mainstay is stepwise reduction of immunosuppression, guided by the plasma viral load, to restore BK-virus-specific T-cell control; this clears the virus in about 80 per cent of patients. Aciclovir and ganciclovir have no useful activity against BK virus, a randomised trial of levofloxacin showed no effect, and increasing immunosuppression would worsen replication.
High priorityClinical scenarioA kidney transplant recipient, nine months post-transplant and still on full immunosuppression after earlier rejection episodes, has a rising serum creatinine and a rising BK virus load. Outline the specimens used, the screening schedule, and the management.
Model answer
A complete answer separates the specimen used for decisions from the one used for screening, states the surveillance schedule, and makes management hinge on immunosuppression.

Specimens

The plasma BK virus DNA load is the decision marker: virus in the blood reflects significant renal replication and is what triggers and monitors treatment. Urinary shedding is near-universal in reactivation, so it is sensitive but not specific, and a high urine load alone does not establish nephropathy. Proven nephropathy requires a renal biopsy with viral cytopathic change and positive SV40 large T antigen immunohistochemistry, taking at least two cores including medulla because the disease is focal.

Screening schedule

All kidney transplant recipients are screened for plasma BK virus DNA at intervals: conventionally monthly until about nine months after transplant, then every three months until two years. A sustained plasma load above 10,000 copies per millilitre is taken as presumptive nephropathy and prompts intervention before the graft is damaged.

Management

The mainstay is stepwise reduction of immunosuppression to restore BK-virus-specific T-cell control: reduce the antimetabolite to no more than half its dose and lower the calcineurin-inhibitor target, which clears the virus in around 80 per cent of patients. There is no antiviral of proven benefit, and adjuncts are reserved for failure of reduction. The important caveat is concurrent acute rejection: if rejection coexists, it is treated first and immunosuppression reduced only afterwards, because the two conditions demand opposite changes.
High priorityClinical scenarioDescribe BK-virus haemorrhagic cystitis after allogeneic haematopoietic stem cell transplantation, including its distinction from early cystitis and its management.
Model answer
Features

BK-virus haemorrhagic cystitis is high-level replication of BK virus in the urothelium, causing denudation and bleeding of the bladder lining. It is of late onset, some two to twelve weeks after engraftment, and is defined by the combination of cystitis symptoms (dysuria, frequency, suprapubic pain), visible haematuria with clots, and a high urine BK virus load. Two transplant-specific factors amplify it: prior urotoxic conditioning, in which cyclophosphamide and its metabolite acrolein damage the bladder epithelium, and the inflammatory surge of immune reconstitution at engraftment.

Distinction from early cystitis

Early haemorrhagic cystitis, occurring in the first days after transplant, is due to conditioning toxicity alone and is brief; it is not caused by BK virus. The later onset, the high urine BK load and the timing around engraftment separate BK-virus cystitis from this earlier urotoxic form.

Management

Management is largely supportive: hydration, bladder irrigation, evacuation of clots, and transfusion of platelets or red cells as needed, while returning cellular immunity brings the infection under control. There is no antiviral of proven benefit. Reducing immunosuppression, the mainstay in renal nephropathy, is constrained here by the risk of graft-versus-host disease.
High priorityClinical scenarioHow is BK-virus-associated nephropathy distinguished from acute rejection in a kidney transplant recipient, and why does the distinction matter?
Model answer
Why it matters

The two conditions look alike but demand opposite treatment. Both present as graft dysfunction with a rising creatinine and both show an interstitial inflammatory infiltrate with tubulitis on biopsy, yet nephropathy is treated by reducing immunosuppression while rejection is treated by augmenting it. Choosing wrongly harms the graft: cutting immunosuppression in rejection accelerates it, and increasing it in nephropathy fuels viral replication.

How they are distinguished

A high and rising plasma BK virus load points to nephropathy, which is then confirmed on biopsy by viral cytopathic change with positive SV40 large T antigen immunohistochemistry. Acute rejection is favoured by features such as endarteritis and, in antibody-mediated rejection, C4d deposition along peritubular capillaries, in the absence of viral staining. The two can coexist, and biopsy with the SV40 stain is what separates them. When both are present, rejection is treated first and immunosuppression reduced only afterwards.
High priorityExam-styleDescribe the pathogenesis of BK-virus-associated nephropathy, and the specimens preferred for screening versus diagnosis. [10]
Model answer
Pathogenesis

BK virus persists for life in the renal tubular epithelium and urothelium and is held in check by cellular immunity. After kidney transplantation the immunosuppression needed to protect the graft permits uncontrolled lytic replication, and the replicating virus is frequently donor-derived, carried in with the kidney. Infected tubular cells enlarge with intranuclear inclusions, round up and slough into the urine as decoy cells, and lyse, releasing virus and provoking an interstitial inflammatory infiltrate. The process is graded through three histological stages, from early cytopathic change with little inflammation, through interstitial inflammation and tubulitis, to tubular atrophy and fibrosis, the last representing irreversible scarring and graft loss.

Specimens for screening versus diagnosis

Screening uses the plasma BK virus DNA load, which reflects renal replication and is the marker that triggers pre-emptive treatment; urine load and decoy cells are more sensitive but less specific, useful as a first filter rather than a decision point. Diagnosis of proven nephropathy is histological: a renal biopsy showing viral cytopathic change with an inflammatory infiltrate, confirmed by SV40 large T antigen immunohistochemistry. Because the infection is focal and favours the medulla, at least two cores including medulla are taken, and a negative stain does not exclude early disease.
MCQ
BK virus is directed to the urinary tract rather than the brain because it:
- A. Uses the serotonin 5-HT2A receptor on glial cells
- B. Requires the CD4 receptor on lymphocytes
- C. Replicates only at the low temperature of the skin
- D. Integrates exclusively into hepatocyte DNA
- E. Binds gangliosides on renal and urothelial cells
Show answer
Correct answer: E
Why E

BK virus attaches to branched gangliosides (GT1b and GD1b) displayed on renal tubular epithelium and urothelium and enters by caveolin-dependent endocytosis, which directs it to the urinary tract. JC virus, by contrast, uses a sialylated glycan with the serotonin 5-HT2A receptor and a clathrin route into glial cells, which is why it targets the brain. The other options describe unrelated viruses.
MCQ
Decoy cells on the urine cytology of a transplant recipient are:
- A. Malignant urothelial cells indicating a high-grade invasive bladder carcinoma
- B. Epithelial cells with intranuclear inclusions shed in BK reactivation
- C. Cytomegalovirus-infected owl-eye cells
- D. Eosinophils indicating allergic interstitial nephritis
- E. Red-cell casts indicating glomerulonephritis
Show answer
Correct answer: B
Why B

Decoy cells are infected tubular and urothelial cells bearing ground-glass intranuclear inclusions, shed into the urine during BK-virus reactivation; they are a sensitive but non-specific marker of replication. They are not malignant cells, are distinct from the owl-eye cells of cytomegalovirus, and have nothing to do with eosinophils or red-cell casts.
MCQ
Four weeks after an allogeneic stem-cell transplant, and after engraftment, a patient develops painful haematuria, and BK virus is detected at high level in the urine. Which statement best fits this presentation?
- A. This is late-onset BK polyomavirus haemorrhagic cystitis, distinct from the early cystitis caused directly by conditioning agents such as cyclophosphamide, and managed mainly with supportive care as immunity recovers
- B. This is early conditioning-related chemical cystitis from cyclophosphamide, which characteristically begins several weeks after engraftment and is confirmed by the high level of BK virus that is found in the urine
- C. This is BK polyomavirus-associated nephropathy identical to the renal-allograft disease, and the high urinary BK level alone is sufficient to diagnose it without any need to measure the plasma BK viral load
- D. This is cytomegalovirus haemorrhagic cystitis, the commonest cause of late haematuria after a stem-cell transplant, and it should be treated promptly with ganciclovir guided by the urinary BK result
- E. The high urinary BK level confirms invasive disease in every case, because BK viruria is rare after transplant and is always accompanied by symptomatic haemorrhagic cystitis whenever it is detected in the urine after conditioning
Show answer
Correct answer: A
Two cystitis patterns after stem-cell transplant

Early (first days, around conditioning): chemical cystitis caused directly by urotoxic conditioning agents (cyclophosphamide, ifosfamide, busulfan).

Late (after engraftment, typically weeks 3 to 6): BK polyomavirus haemorrhagic cystitis, with a high urinary BK load, as in this case.

The timing separates the two, which is why option B (placing chemical cystitis weeks after engraftment) is wrong.

Diagnosis and management

BK haemorrhagic cystitis is a bladder disease, not the renal-allograft nephropathy (option C), and the urinary load alone does not equate to disease: 50 to 80 per cent of stem-cell recipients have high viruria but fewer than 20 per cent develop cystitis, so viruria is necessary but not sufficient (option E is wrong). Management is largely supportive: hydration, bladder irrigation, analgesia and transfusion as needed; no antiviral is of proven benefit, though cidofovir is sometimes tried. Option D is wrong because this is BK, not CMV, disease.
MCQ
Which specimen and result triggers pre-emptive treatment of BK virus in a kidney transplant recipient?
- A. A single urine sample showing decoy cells
- B. Urine BK virus DNA above 10,000 copies per millilitre on cytology
- C. BK virus IgG seroconversion in the recipient
- D. Plasma BK virus DNA above 10,000 copies per millilitre
- E. An isolated doubling of the serum creatinine
Show answer
Correct answer: D
Why D

The plasma BK virus DNA load is the decision marker, because virus in the blood reflects significant renal replication; a sustained plasma load above 10,000 copies per millilitre is taken as presumptive nephropathy and prompts pre-emptive reduction of immunosuppression. Urinary shedding and decoy cells are sensitive but not specific, serology does not guide treatment, and a creatinine rise alone is non-specific.
MCQ
Proven BK-virus-associated nephropathy on renal biopsy is confirmed by:
- A. Congo red staining for amyloid
- B. C4d staining of peritubular capillaries
- C. Immunohistochemistry for SV40 large T antigen
- D. Silver staining for fungal hyphae
- E. Immunostaining for cytomegalovirus early antigen
Show answer
Correct answer: C
Why C

Proven nephropathy requires viral cytopathic change with positive immunohistochemistry for the SV40 large T antigen, using an antibody that cross-reacts with the BK-virus large T antigen to stain infected tubular nuclei. C4d marks antibody-mediated rejection, not BK disease; Congo red, silver and cytomegalovirus stains identify unrelated processes.
MCQ
Regarding drug therapy for BK-virus-associated nephropathy, which statement is correct?
- A. Levofloxacin reliably clears the virus from blood
- B. No specific antiviral is of proven benefit
- C. Cidofovir is curative and free of toxicity
- D. Ganciclovir is the treatment of choice
- E. Aciclovir prophylaxis prevents nephropathy
Show answer
Correct answer: B
Why B

No antiviral has proven benefit against BK virus, and management rests on reducing immunosuppression. A randomised trial of levofloxacin showed no effect on viral load; cidofovir gives inconsistent results and carries nephrotoxicity and uveitis; and ganciclovir and aciclovir have no useful activity against BK virus.