Monday, November 25, 2013

Does JC Virus Nephropathy Exist?

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.


Anonymous said...

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

Anonymous said...

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