Treatment of BK virus‐associated nephropathy with CMX001 after kidney transplantation in a young child

Abstract

NC, with renal failure secondary to bilateral dysplastic kidneys, received an LRD renal transplant (tx) at 17 months of age. Her early post-tx course was complicated by persistently elevated blood polyoma BK virus DNA loads. A protocol biopsy at six months post-transplant revealed BKVAN. Blood viral loads did not respond to decreased immunosuppression or treatment with ciprofloxacin and leflunomide. Six months post-tx, her serum creatinine began to rise and we sought experimental therapy to prevent the loss of her graft. At seven months post-tx, with FDA approval under an eIND, the patient was started on a 36-wk course of treatment with the investigational drug. The patient is now more than 24 months after stopping treatment with CMX. BKV viral DNA loads remain at low, but still detectable levels. Urine viral loads have declined, but remain elevated. EBV DNA loads become undetectable. The patient's serum creatinine has declined back to a baseline of 0.5-0.7 mg/dL and has been stable for two yr. Renal function was preserved in association with the use of CMX001 to treat BKV nephropathy in a young pediatric kidney transplant recipient. There were no serious adverse events associated with the use of CMX001. This novel medication may be of value in the treatment of BKVAN in pediatric renal transplant recipients.

BK virus nephropathy in renal transplant recipients

“…The advantage of CMX001 is its potency against all DNA viruses with no reported nephrotoxicity and ease of oral administration . Reisman et al . reported its successful use in a paediatric RTR with BKVN …”

“…The advantage of CMX001 is its potency against all DNA viruses with no reported nephrotoxicity and ease of oral administration. 55 Reisman et al 56 reported its successful use in a paediatric RTR with BKVN. 56 Papadopoulou et al 57 have reported developing virusspecific T lymphocytes (VST) from the donor that can recognize antigens found in five common viruses encountered by immunosuppressed hosts (viz.…”

BK virus: Current understanding of pathogenicity and clinical disease in transplantation

“…After a 36‐week treatment course, BK viral load levels declined, although remained detectable. Epstein‐Barr virus (EBV) became undetectable, and renal function improved to baseline, remaining stable for a further 2‐year follow‐up, with no serious drug related adverse effects observed . In 2015, a further report showed stabilisation of renal function and resolution of viraemia in a HSCT recipient with biopsy‐proven BKVN .…”

Efficacy and adverse effects of cidofovir for treatment of BK virus infection in kidney transplant recipients

“…Invitro study showed that brincidofovir can inhibit BK virus replication, protein expression and production of new virion in human urothelial cell with high cellular absorption less toxicity (63). Some case reports demonstrated the efficacy of brincidofovir in BK-VAN (64,65). Recently, the data on brincidofovir treatment of cytomegalovirus (CMV) infection has been presented (66,67).…”