Research Group
- Dr. Volker Nickeleit, Principal Investigator
Location
- The University of North Carolina, Chapel Hill, USA
Title
- BK-Virus Load Measurements in Kidneys: New Strategies for Assessing the Risk of BK-Virus Nephropathy
Renal transplantation has made significant progress over the last 30 years. Not only have graft survival rates vastly improved and acute rejection episodes diminished, but high-risk patients, such as those requiring transplantation across ABO incompatible blood-group barriers, are now also eligible for transplantation. These remarkable strides are due to the development of new, highly potent immunosuppressive strategies. However, progress comes at a price. Previously uncommon infections have emerged and turned into serious complications post-transplantation. One of these infectious complications is polyomavirus nephropathy caused by BK-viruses. Practically non-existent in the 1980s, so-called BK-virus nephropathy (BKN) is currently diagnosed in 1% to 5% of renal allograft recipients world wide. BK-virus nephropathy leads to graft failure in up to 52% of patients.
It is commonly believed that BK-virus nephropathy is due to the re-activation of latent viruses. However, little is known about specific risk factors promoting the disease. In recent years, we have learned that an early diagnosis of BKN, which depends on the detection of characteristic histological changes, is required for favourable long-term graft function.
Our study aims to characterize risk factors and diagnostic strategies to better understand BKN and to ultimately limit graft loss. We will use quantitative PCR analyses in order to measure BK-virus loads in renal tissue samples. One objective of our study protocol is to define (currently undetermined) reference ranges of latent BK-virus loads in kidneys. We will test the hypothesis whether certain donor organs containing high loads of dormant BK-virus are prone to the development of viral nephropathy. This can potentially define a new measurable risk factor. In addition, we will determine whether post-transplantation BK-virus load measurements by PCR allow for the diagnosis of BKN in very early stages prior to the development of histological changes in allografts. If applicable, diagnostic strategies could be amended by incorporating tissue PCR analyses into the routine work-up of allograft biopsies. Thus, we hope to shed additional light on the biology of BK-virus nephropathy. Our findings can have direct clinical implications and help to prevent the detrimental impact of BK-virus nephropathy on renal allograft survival.