Extracorporeal photopheresis in BK virus infection after kidney transplantation: current evidence and emerging clinical applications

Abstract BK polyomavirus (BKPyV) infection is a major complication after kidney transplantation, with no approved antiviral therapy and management reliant on immunosuppression reduction, which increases rejection risk. This review outlines the biological rationale for extracorporeal photopheresis (ECP) in infectious settings and critically appraises the current evidence for its use in BKPyV replication and BKPyV-associated nephropathy (BKPyVAN). ECP is an immunomodulatory therapy that induces apoptosis of apheresis-isolated mononuclear cells via ex vivo exposure to a photoactivatable agent and UVA light; reinfusion promotes tolerogenic dendritic cells, regulatory T-cell expansion, and cytokine modulation. Its antiviral potential was first observed in cytomegalovirus, with ECP linked to reduced viral burden in heart, lung, and hematopoietic transplantation. Experience in BKPyV is more limited, restricted to small case series and reports, where ECP combined with immunosuppression reduction was associated with sustained reductions in viremia, reaching > 99% in individual series, without increased rejection. These uncontrolled, confounded designs cannot isolate an ECP-specific antiviral effect, and the proposed antiviral mechanism remains hypothetical. ECP may be a promising adjunctive strategy in selected high-risk patients with persistent BKPyV viremia or BKPyVAN, but prospective, controlled studies are needed to confirm efficacy and define optimal use.