- Dr. Parmjeet Randhawa, Principal Investigator
- Dr. Sidney Finkelstein, Co-Investigator
- University of Pittsburgh, Pittsburgh, USA
- Polyomavirus BK, JC and SV40 in the Kidney: Pathogenesis, Early Diagnosis and Improving Graft Outcome
The kidney is a common site for latent infection by polyomavirus. In healthy subjects with a functioning immune system, this latent infection is not associated with any symptoms. However, in kidney transplant recipients who receive potent immunosuppressive drugs to prevent rejection of the graft, latent virus can reactivate and result in a disease called polyomavirus nephropathy. At present, this disease is diagnosed at a rather late stage, and frequently results in loss of the transplanted organ.
This grant proposal will focus on early diagnosis of currently unrecognized and milder forms of this disease using the polymerase chain reaction (PCR), a technique that can amplify minute quantities of virus to a level that can be detected easily in the laboratory. Once a diagnosis of viral nephropathy has been made, physicians reduce the dosage of immunosuppressive drugs. This allows the patient’s immune system to recover and try to get rid of the viral infection. We have recently started giving a drug called cidofovir to help combat polyomavirus infection in the kidney. Unfortunately, this drug can be quite toxic to the kidney if given for a prolonged period. The PCR test described above will allow us to determine quickly when polyomavirus has been eliminated from the patient’s kidney, and thus minimize exposure to this potentially harmful drug. We will also use virus growing in the laboratory to identify less toxic alternative drugs for possible clinical use in patients with polyomavirus nephropathy.
Finally, the PCR test will be used to understand the changes in viral genetic configuration that allow transformation of silent or latent viral infection to an active disease, which interferes with optimal functioning of the transplanted kidney.