title: Treatment of refractory BK virus-associated nephropathy with cidofovir.
abstract: BK virus-associated nephropathy (BKVN) has become recognized as an important cause of allograft dysfunction in renal transplant recipients and despite reduction in immunosuppression, 30-40% of recipients ultimately progress to allograft loss. Cidofovir is an antiviral agent that demonstrates in vitro activity against murine polyomavirus and has been proposed for treatment of BKVN in renal allograft recipients. We describe the clinical course, renal function, serial renal histology and urine and blood viral load measurements in two consecutive patients with refractory BKVN who were treated with low-dose cidofovir (0.25 mg/kg IV). In each case, renal dysfunction and BK viral load progressed despite reduced immunosuppression, and persistent BK virus infection was documented in serial renal allograft biopsy specimens. Administration of low-dose cidofovir was associated with clearance of BK virus DNA from blood and allograft, and stabilization of renal function in both patients, without significant toxicity. These preliminary data suggest that low-dose cidofovir may be tolerated, even among renal transplant recipients with significant renal dysfunction due to BKVN. Prospective, controlled trials are warranted to further define the optimal dose, toxicity and potential role of cidofovir in renal transplant recipients with BK virus nephropathy.
authors.affiliation: Department of Internal Medicine, Pathology, University of Chicago, Chicago, IL, USA.
authors.forename: Pradeep V
authors.initials: PV
authors.lastname: Kadambi
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Josephson
authors.forename: James
authors.initials: J
authors.lastname: Williams
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Keith R
authors.initials: KR
authors.lastname: Jerome
authors.forename: Shane M
authors.initials: SM
authors.lastname: Meehan
authors.forename: Ajit P
authors.initials: AP
authors.lastname: Limaye
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001739:BK Virus / Q000302:isolation & purification; D000077404:Cidofovir; D003404:Creatinine / Q000097:blood; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000628:therapy; D006630:Hispanic or Latino; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy / Q000821:virology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D027601:Polyomavirus Infections / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000188:drug therapy*; D019562:Viral Load; D044465:White People
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D003404:Creatinine; D000077404:Cidofovir