Treatment of polyomavirus infection in kidney transplant recipients: a systematic review.
BACKGROUND.: Polyomavirus-associated nephropathy (PVAN) is an important cause of kidney graft loss but there is no consensus on its management. This study aimed to systematically document all published treatments for PVAN to determine the most effective therapy. METHODS.: A computerized search in MEDLINE, EMBASE, and Cochrane databases (1950-2008) was performed. References from review articles and published abstracts from the American Transplant Congress (2005-2008) were also included. Study selection criteria included (a) population: adult (>18 years) kidney-only, primary or repeat renal transplant recipients; (b) setting: polyoma viruria, viremia or biopsy-proven PVAN or both; and (c) treatment: immunosuppression reduction alone or with adjuvant agents. The primary outcome was graft failure rate, and secondary outcomes included acute rejection rate, elimination of viruria and viremia, graft function, patient survival, and adverse events. RESULTS.: Of 555 identified citations, 40 studies examining the effect of immunosuppression reduction alone or in combination with cidofovir, leflunomide, intravenous immunoglobulin, or ciprofloxacin were included for appraisal. Pooled results found a death-censored graft loss rate of 8/100 patient-years for immunosuppression reduction alone and 8 and 13/100 patient-years for the addition of cidofovir or leflunomide, respectively. CONCLUSIONS.: There does not seem to be a graft survival benefit of adding cidofovir or leflunomide to immunosuppression reduction for the management of PVAN. However, the evidence base is poor and highlights the urgent need for adequately powered randomized trials to define the optimal treatment of this important condition.
Johnston
Olwyn
O
Division of Nephrology, University of British Columbia, Vancouver, BC, Canada. Olwyn.Johnston@vch.ca
Jaswal
Dharmvir
D
Gill
John S
JS
Doucette
Steve
S
Fergusson
Dean A
DA
Knoll
Greg A
GA
D000998:Antiviral Agents / Q000627:therapeutic use*; D001739:BK Virus / Q000187:drug effects; D000077404:Cidofovir; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000502:physiology; D063065:Organophosphonates / Q000627:therapeutic use*; D027601:Polyomavirus Infections / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012086:Reoperation; D015996:Survival Rate; D017211:Treatment Failure; D014412:Tumor Virus Infections / Q000188:drug therapy*; D014766:Viremia / Q000188:drug therapy
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D063065:Organophosphonates; D003596:Cytosine; D003404:Creatinine; D000077404:Cidofovir