The Microbiologist nearly fell off his chair… people were rarely that polite when calling…
“Certainly, what can I help you with?” he replied, feeling immediately predisposed to being happy and helpful. (A very weird and unfamiliar feeling for the Microbiologist!)
“I have a complex patient who had a kidney transplant about 6 months ago who keeps getting UTIs. She has had a number of positive urine cultures and she feels better after being treated, but when the antibiotics stop, she quickly becomes symptomatic again. We’re wondering where we go from here. Should we try a longer course of antibiotics to see if that helps or would she benefit from antibiotic prophylaxis?”
The Microbiologist had been listening intently.
“This could be BK virus infection causing ureteral stenosis. Have you imaged the transplanted renal tract?”
“Beaky what virus?” asked the Junior.
And it had been going so well….
BK Virus is a double-stranded DNA virus, in the polyomavirus family, that infects about 90% of the population by the time they are adults.
B and K were the initials of the first patient from whom the virus was first isolated, hence the name BK Virus. (Science, and microbiology in particular, really does use some stupid nomenclature at times!)
After initial infection it remains latent in kidney tubular epithelial cells; here it can reactivate and be detectable in the urine of up to 20% of people who are completely healthy and have no symptoms. However, in some immunocompromised patients it can cause severe infections when it reactivates.
How does BK Virus infection present?
- Nephropathy – up to 10% of post-renal transplant patients, especially if taking Tacrolimus or Mycophenolate immunosuppression to prevent rejection of the transplanted kidney. Caused by reactivation and damage to kidney cells, detected by worsening kidney function on blood tests (Urea & Electrolytes)
- Ureteral stenosis – up to 3% of post-renal transplant patients, causes narrowing of the tube that connects the kidney to the bladder, which can prevent the kidney draining. Caused by virus reactivating and damaging ureteral cells, predisposing to urine infections in the stagnant urine as well as damage to the kidney if it can’t drain properly
- Haemorrhagic cystitis – up to 15% of bone marrow transplant patients develop severe cystitis which presents with pain on passing urine, frequency, urgency and blood and clots in the urine. Caused by virus reactivating in bladder cells which are then attacked by the immune system when the bone marrow starts to work again (known as immune reconstitution)
Note: the damage to the kidney in renal transplant patients does not cause any pain because the transplant itself does not have a nerve supply.
Very rarely BK Virus can cause more widespread infections of the lungs and central nervous system in immunosuppressed patients.
How is BK Virus infection diagnosed?
The initial infection with BK Virus is asymptomatic. In bone marrow transplant patients reactivation causes symptoms that suggest a UTI. However, in renal transplant patients no symptoms occur as the graft does not have a nerve supply and so cannot feel pain; reactivation should be suspected if their renal function based on blood tests (U&Es) starts to deteriorate.
The diagnosis of BK Virus infection is made by looking for virus in urine and blood by PCR. It can be difficult to prove that BK Virus infection is the cause of the deterioration in renal function in renal transplant patients as virus can be detected in urine without causing disease; however detection of the virus in blood is highly suggestive of infection. It is also possible to diagnose BK Virus infection through histopathology of renal biopsy samples, showing viral damage to kidney cells (known as inclusion bodies).
How is BK Virus infection treated?
Unfortunately, there is no specific treatment for BK Virus infection. The only way to control reactivation in immunosuppressed patients is to try to reverse as much of the immunosuppression as possible. This can be difficult as reducing the immunosuppression can lead to the body rejecting the transplant. Balancing infection against graft rejection can be a very tricky business, and isn’t always successful, resulting in loss of the kidney in 1-10% of patients.
Another approach to BK Virus management is to screen the urine of transplant patients regularly for virus and if it is detected then pre-emptively try and reduce the immunosuppression to bring it back under control. Again, there needs to be a careful balance between infection and graft rejection though.
The treatment of ureteral stenosis is usually a combination of both reducing immunosuppression as well as surgical correction of the narrowing in the ureter.
The management of haemorrhagic cystitis is much more difficult as there isn’t an option to reduce immunosuppression; the problem is actually the immune response attacking the bladder. In this situation supportive care with hyperhydration (to keep urine flowing) and bladder irrigation to remove virus, pain control and maintenance of platelet counts to control bleeding are all important. With good supportive care the cystitis should settle by itself and the virus become latent again.
The Microbiologist carefully explained the role of BK Virus to the Junior Doctor who listened intently. They discussed the need to send urine and blood samples for PCR and get some imaging to look at the renal tract.
At the end of the conversation the Junior said, “Thanks so much for your help. I’ll get the tests off right away. May I please call you to discuss the results when they are back?”
Ah… if only we could bottle those manners… thought the Microbiologist… the day was looking up after all….
If you need to know the answers here you go:
Captain Beaky, Timid Toad, Reckless Rat, Artful Owl and Batty Bat...
and if you need to waste 4.20 minutes of your time listen to this... you'll never believe this was in the Hit Charts in 1980s!