Author:

Keywords:

Adult, Aged, Antiviral Agents, BK Virus, Chemotherapy, Adjuvant, Cytosine, Dose-Response Relationship, Drug, Female, Humans, Immunosuppressive Agents, Kidney Transplantation, Male, Middle Aged, Nephritis, Interstitial, Phosphonic Acids, Polyomavirus Infections, Treatment Outcome, Tumor Virus Infections, Science & Technology, Life Sciences & Biomedicine, Surgery, Transplantation, BK polyomavirus, cidofovir, interstitial nephritis, renal transplantation, VIRUS-ASSOCIATED NEPHROPATHY, PHARMACOKINETICS, INFECTION, RISK, Cidofovir, Organophosphonates, 11 Medical and Health Sciences, 3202 Clinical sciences, 3204 Immunology

Abstract:

BK virus interstitial nephritis (BKVIN) is a serious complication after kidney grafting, necessitating drastic reduction of immunosuppressive therapy in order to enable viral clearance. Despite these measures, progressive graft dysfunction and graft loss occur in the majority of recipients. We diagnosed BKVIN in 21 recipients grafted between 1998 and 2004. Eight of 21 patients were treated with weekly, adjuvant low-dose cidofovir in addition to reduction of immunosuppressive therapy. BKVIN caused irreversible deterioration of graft function in all patients but renal function stabilized after antiviral treatment (creatinine clearance: 51.8-32 mL/min; p=0.001) and no graft loss occurred in cidofovir-treated recipients during 24.8 (8-41) months follow-up. Peak serum cidofovir concentrations were dose-dependent and attained approximately one-tenth of thein vitroEC50 for cidofovir against BK-virus, while pre-treatment with probenecid did not alter peak serum concentrations nor affected the incidence of nephrotoxicity. In fact, no cidofovir-related renal toxicity occurred; few patients had minor transient side effects (nausea, skin rash). In contrast, 9 of 13 patient who received no adjuvant cidofovir therapy lost their graft after median 8 (4-40) months. In this selected group of recipients with BKVIN, the use of adjuvant low-dose cidofovir therapy resulted in prolonged graft survival and stabilized graft function.