Persistent BK Viremia Leads to BK Virus Nephropathy-Associated Graft Failure in a Simultaneous Liver-Kidney (SLK) Transplant Recipient on Ustekinumab

Introduction: BK virus-associated nephropathy(BKVAN) remains a significant cause of renal graft failure, typically managed by reducing immunosuppression. Ustekinumab, an IL-12/23 inhibitor used for severe Crohn’s disease, yet its safety in solid organ transplant is not well established. We present a case of persistent high-grade BK viremia and renal graft failure in an SLK recipient on Ustekinumab despite low-dose tacrolimus monotherapy. Case Description: A 70-year-old male with severe Crohn’s disease on ustekinumab, cryptogenic cirrhosis, and ESRD due to HRS underwent SLK transplant.Induction included basiliximab, and maintenance immunosuppression consisted of mycophenolate mofetil(MMF), tacrolimus, and prednisone. Ustekinumab (90mg SC q8w) was continued post-transplant. At 1 month, BK viruria (17,000 IU/ml) emerged, followed by BK viremia (1,660 IU/ml) at month 2. Despite MMF reduction, lower tacrolimus troughs, and low-dose prednisone, viremia worsened, peaking at >1,000,000IU/ml. Biopsy confirmed polyomavirus nephropathy (PVN class II) without evidence of rejection. MMF and prednisone were discontinued, IVIG was initiated, and Tacrolimus was maintained at 4-5 ng/ml troughs. Despite these measures, high-grade viremia and worsening allograft function persisted. Given persistent high-grade viremia and concern for impaired viral clearance, Ustekinumab was held for 4 months, during which viral load declined significantly to 45,000 IU/mL. Ustekinumab was reintroduced due to worsening Crohn’s symptoms, and viremia subsequently persisted, accompanied by progressive allograft dysfunction. Repeat allograft biopsy at 18 months after transplant revealed advanced PVN (70% IFTA), and GFR declined to <15ml/min. Discussion: Ustekinumab is a human IgG1κ monoclonal antibody that blocks the p40 subunit of IL-12/23, impairing Th1 and cytotoxic T-cell responses critical for antiviral defense.In this SLK recipient with Crohn’s disease, high-grade BKV and BKVAN progressed despite low-dose tacrolimus monotherapy. BKV load declined following Ustekinumab withdrawal and rebounded upon reintroduction due to relapse, suggesting impaired viral clearance associated with IL-12/23 inhibition. This case highlights the clinical conundrum of using IL-12/23 inhibitors to maintain Crohn's remission without compromising graft function amid ongoing BK replication.