Prospective Study of Polyomavirus Type BK Replication and Nephropathy in Renal-Transplant Recipients
Hans H. Hirsch, M.D., Wendy Knowles, Ph.D., Michael Dickenmann, M.D., Jakob Passweg, M.D., Thomas Klimkait, Ph.D., Michael J. Mihatsch, M.D., and Jürg Steiger, M.D.
Background Nephropathy associated with the polyomavirus typeBK (BKV) nephropathy has emerged as a cause of allograft failurelinked to immunosuppressive regimens containing tacrolimus ormycophenolate mofetil. The presence of viral inclusions, knownas "decoy cells," in urine and the presence of BKV DNA in plasmahave been proposed as markers for the replication of BKV andassociated nephropathy, but data from prospective studies havebeen lacking.
Methods In a prospective, single-center study, we followed 78renal-transplant recipients who were receiving immunosuppressivetherapy that included tacrolimus (37 patients) or mycophenolatemofetil (41 patients). Urine was tested for the presence ofdecoy cells at routine visits. BKV DNA was measured 3, 6, and12 months after transplantation and whenever decoy cells weredetected. The viral load in plasma was quantified with the useof a real-time polymerase-chain-reaction method. Renal biopsywas performed if allograft function deteriorated.
Results Twenty-three patients had decoy-cell shedding a medianof 16 weeks after transplantation (range, 2 to 69), 10 patientshad BKV viremia at a median of 23 weeks (range, 4 to 73), and5 had BKV nephropathy at a median of 28 weeks (range, 8 to 86).KaplanMeier estimates of the probability of decoy-cellshedding, viremia, and nephropathy were 30 percent (95 percentconfidence interval, 20 to 40 percent), 13 percent (95 percentconfidence interval, 5 to 21 percent), and 8 percent (95 percentconfidence interval, 1 to 15 percent), respectively. Antirejectiontreatment, particularly with corticosteroids, was associatedwith BKV replication and nephropathy. The viral load in plasmawas higher in patients with BKV nephropathy than in those withoutnephropathy (P<0.001 by the MannWhitney test). BKVantibodies were detected in 77 percent of the 78 patients beforetransplantation, including 4 of 5 with BKV nephropathy.
Conclusions BKV nephropathy in renal-transplant recipients representsa secondary infection associated with rejection and its treatmentin most cases and could be monitored by measuring the viralload in plasma.
Source Information
From the Division of Infectious Diseases (H.H.H.), the Institute for Medical Microbiology (H.H.H., T.K.), and the Divisions of Nephrology and Transplantation Immunology (M.D., J.S.) and Hematology (J.P.) and the Institute for Pathology (M.J.M.), University of Basel, Basel, Switzerland; and the Enteric, Respiratory, and Neurological Virus Laboratory, Central Public Health Laboratory, London (W.K.).
Address reprint requests to Dr. Hirsch at the Division of Infectious Diseases, Department of Internal Medicine, University Hospitals Basel, Petersgraben 4, CH-4031 Basel, Switzerland, or at hans.hirsch{at}unibas.ch.
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