title: Intermediate-dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy.
abstract: BK virus allograft nephropathy (BKVAN) is a rising complication in kidney transplant recipients. Reducing immunosuppression has been the initial form of therapy in most cases, but is not always associated with improvement in graft function. Anti-viral therapy with low-dose cidofovir (0.25-0.42 mg/kg/dose) has been used successfully in some patients, but dose-related nephrotoxicity has limited its use. We present our experience with 3 kidney transplant recipients diagnosed with BKVAN who received intermediate-dose cidofovir (0.75-1.0 mg/kg/dose) without probenecid, and without concomitant nephrotoxicity. Three female patients, ages 8, 19 and 20 yr, presented with elevated serum creatinine (SCr) values, BK virus stain positive on renal biopsy and high plasma BK viral loads. As a result of viral loads being >2 million copies/ml in two patients and a lack of response to reduction in immunosuppression in the third, we initiated therapy with low-dose cidofovir. Because of persistent positive BK stain and positive plasma viral load, we then administered intermediate-dose cidofovir, without probenecid, for several subsequent doses (seven to 15 infusions till date). All patients tolerated the intermediate-dose cidofovir with no significant rise in SCr during the course of the infusions. The most recent SCr values in all three patients were improved from those at the initial diagnosis of BKVAN. All three patients showed a marked drop in BK viral loads when on intermediate-dose cidofovir, with complete clearing of viremia in two patients. In our experience, intermediate-dose cidofovir without probenecid, used judiciously, is not associated with additional nephrotoxicity and may provide an additional alternative for treatment.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610-0296, USA.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Araya
authors.forename: Judy F
authors.initials: JF
authors.lastname: Lew
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fennell
authors.forename: Richard E
authors.initials: RE
authors.lastname: Neiberger
authors.forename: Vikas R
authors.initials: VR
authors.lastname: Dharnidharka
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001739:BK Virus / Q000235:genetics; D001706:Biopsy; D002648:Child; D000077404:Cidofovir; D000075202:Contraindications; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000473:pathology*; D009395:Nephritis, Interstitial / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D063065:Organophosphonates / Q000008:administration & dosage* / Q000627:therapeutic use; D027601:Polyomavirus Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D011339:Probenecid; D014184:Transplantation, Homologous; D014412:Tumor Virus Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D014528:Uricosuric Agents
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D014528:Uricosuric Agents; D003596:Cytosine; D000077404:Cidofovir; D011339:Probenecid