Does JC Virus Nephropathy Exist?

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The JC virus is a member of the
Polyomavirus family, which includes the BK virus.  It infects about 80% of healthy adults and
establishes latency in renal tissue. It was first isolated in 1971 from the
brain of a patient (initials JC), with Hodgkin’s lymphoma who died of
progressive multifocal leukoencephalopathy. While working on a transplant
service some years ago and reviewing screening results for polyoma virus, I
noticed a high rate of JC viruria which didn’t always correlate with BK
replication. Allograft function always seemed to remain excellent and I was
unsure of the relevance of the results. Thankfully we soon stopped checking
polyoma viral loads in the urine so I stopped worrying about a test I didn’t
know how to interpret. I have wondered since does JC Nephropathy even exist so
decided look at the evidence.

A few points to note regarding JC Virus and renal transplant patients:
·        
The relationship between JC virus replication and
immunosuppression is less well defined than with BK virus. A study of renal
transplant recipients and matched non-immunosuppressed controls had similar
rates of JC viruria (but more high levels in the transplant patients).
Also, JC viruria appears to respond less well to immunosuppression reduction.
·        
Dan Brennan’s group recently prospectively reviewed the interaction between BK and JC virus in 200 renal
transplant patients in the first year. They detected BK and JC viruses in the urine of 35 and 16% of
transplant recipients respectively with BK viral load being 400 times higher
than JC. Interestingly, the presence of BK viruria made concurrent JC viruria
significantly less likely and no episodes of JC viremia or JC nephropathy were
observed. Moreover, a lower acute rejection rate and improved graft survival
was observed among those who had JC viruria which was independent of the lower
BK levels.
·        
Regarding JCV viremia in the renal transplant
recipients, it seems to be uncommon (maybe 10-15%), transient and low level. Rates
may not be different to immunocompetent individuals and it does not appear to
correlate with renal dysfunction.  Viremia appears to be even less common in
other solid organ recipients.
·        
In the few reported cases of apparent JC
Nephropathy, there has been poor correlation with JC viremia in contrast to the
relationship with BK viremia and BK nephropathy.  A prospective cohort of 980 renal transplant
patients reported >40% JC viruria, 14.5% JC viremia with 0.9% developing JC
Nephropathy. The patients who
were biopsied with JC shedding mostly had stable renal function and were
biopsied due to decoy cell shedding. The few who had a bump in creatinine which
prompted biopsy had other reasons to explain the allograft dysfunction (e.g.
ATN). Reduction of
immunosuppression did not clear viral replication but no graft loss occurred.
·        
Many people in the 1950s-60s were exposed to
contaminated vaccines containing the SV-40 (Simian Virus 40) virus, another
Polyoma virus. The immunohistochemical stain used to diagnose Polyoma Virus
nephropathy on biopsy uses antibodies mostly specific to SV-40 and cannot
distinguish between BK, JC and SV-40 viruses. There is speculation that SV-40
may also potentially cause nephropathy.

Ok enough already, does JC Virus
Nephropathy exist?
…..Probably! Certainly it appears to
be rare and not correlated with BK Nephropathy. It has a different relationship
with immunosuppression from BK Nephropathy and appears to have a favorable
outcome.
So what is the significance of JC
Virus replication post renal transplant?
Very little, at least for
viruria. In fact, patients seem to have less BK replication when JC viruria is
present and there is even a suggestion of a better outcome in patients shedding
JC, which is independent of the lower incidence of BK replication.
Should we screen for JC Virus
replication post kidney transplant?
I don’t see a compelling reason based on our current knowlegde.

2 comments

  1. Nice post Paul. JC was John Cunningham, a nerdy and useless piece of information. This is not a HIPAA violation!
    Andrew Malone

  2. Another great post by Paul Phelan! JC was John Cunningham, a little piece of useless information! this is not a HIPAA violation.
    Andrew Malone

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