Camilla Lorant: BK polyomavirus infection after kidney transplantation: Risk factors, viral transmission and immune response

Abstract

BK polyomavirus (BKPyV) is a significant cause of graft impairment or graft loss following kidney transplantation. BKPyV often causes asymptomatic infection during childhood, after which the virus establishes latency in the uroepithelial cells of the urinary tract. Seroprevalence in adults exceeds 90%. When the immune system is suppressed, the virus may reactivate and cause serious complications such as BKPyV-associated nephropathy (BKPyVAN) with the risk of permanent damage to the kidney. BKPyVAN affects 1-10% of all kidney transplant recipients.

There is currently no effective antiviral treatment against BKPyV. Tapering of immunosuppression, with the increased risk of rejection, is often the only option. Therefore, many transplant centres screen for BKPyV DNAemia after kidney transplantation. Since frequent screening is resource-intensive, it would be of clinical benefit to better predict who will be affected by BKPyV infection and BKPyVAN to more accurately target the screening.

The overall aim of this thesis was to identify risk factors for development of BKPyV to increase the precision of the diagnosis and to improve the clinical outcome in kidney transplant recipients.

In both a retrospective and a prospective study we found that male sex was a risk factor for BKPyVAN or high-level BKPyV DNAemia and in the prospective study we also identified older recipient age as a risk factor.

The incidence was approximately equal in both studies, 4.7% and 4.9%, respectively, despite the fact that screening for BKPyV had been introduced before the second study. It is likely that we found more BKPyV infections after the screening was introduced and also that they were found earlier.

In the prospective study most BKPyV infections were identified to be of donor origin. There was a higher risk of the recipient developing BKPyV infection if the donor had viruria in connection with the transplant. In addition, there was a higher risk of developing BKPyV infection if the donor had high BKPyV antibody levels at transplantation and if the donor and recipient were serologically mismatched.

When analysing immunological markers, a low CD4/CD8 ratio and a positive immune risk profile (CD4/CD8 ratio <1 and CMV seropositivity) in the recipient before transplantation were identified with increased risk of developing BKPyV infection.

In conclusion, this thesis has provided further insight into general and immunological risk factors for development of BKPyV infection after kidney transplantation and knowledge that is of benefit to improve BKPyV screening in the future.