BK Polyomavirus-associated nephropathy – diagnostic and treatment standard

Abstract BK polyomavirus (BKPyV) is recognised as a significant viral complication of kidney transplantation. Prompt immunosuppression reduction reduces early graft failure rates due to BK polyomavirus-associated nephropathy (BKPyVAN), however modulation of immunosuppression can lead to acute rejection. Medium-to-long term graft outcomes are negatively impacted by BKPyVAN, likely due to a combination of virus-induced graft damage and host immune responses against graft alloantigens potentiated by immunosuppression reduction. Kidney biopsy remains the gold-standard diagnostic test, however false negative findings are common due to the focal nature of BKPyVAN. BKPyV DNAemia, as measured by quantitative polymerase chain reaction (qPCR), is established as a screening test but there is at present no (inter)national standardisation of these assays to allow collation and comparison of data between centres. Randomised controlled trials are lacking both in terms of optimal immunosuppression reduction strategies, and for the medications variably used to attempt treatment in clinical practice. Much of the fundamental biology of BKPyV is not yet understood, and further elucidation is required to promote rational direct-acting antiviral drug design. Insights into the role of adaptive immunity in control of BKPyV have informed the design of novel treatments such as adoptive immunotherapies and neutralizing antibodies which require evaluation in clinical studies. Here, we review the current standards of diagnosis and treatment of BKPyVAN and discuss novel developments in the pathophysiology, diagnosis, outcome prediction and management.