Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations.
Polyomavirus-associated nephropathy (PVAN) is an emerging cause of kidney transplant failure affecting 1-10% of patients. As uncertainty exists regarding risk factors, diagnosis, and intervention, an independent panel of experts reviewed the currently available evidence and prepared this report. Most cases of PVAN are elicited by BK virus (BKV) in the context of intense immunosuppression. No specific immunosuppressive drug is exclusively associated with PVAN, but most cases reported to date arise while the patient is on triple immunosuppressive combinations, often comprising tacrolimus and/or mycophenolate mofetil plus corticosteroids. Immunologic control of polyomavirus replication can be achieved by reducing, switching, and/or discontinuing components of the immunosuppressive regimen, but the individual's risk of rejection should be considered. The success rate of this intervention is increased with earlier diagnosis. Therefore, it is recommended that all renal transplant recipients should be screened for BKV replication in the urine: 1) every three months during the first two years posttransplant; 2) when allograft dysfunction is noted; and 3) when allograft biopsy is performed. A positive screening result should be confirmed in <4 weeks and assessed by quantitative assays (e.g. BKV DNA or RNA load in plasma or urine). Definitive diagnosis of PVAN requires allograft biopsy. If PVAN and concurrent acute rejection is diagnosed, antirejection treatment should be considered, coupled with subsequently reducing immunosuppression. The antiviral cidofovir is not approved for PVAN, but investigational use at low doses (0.25-0.33 mg/kg intravenously biweekly) without probenicid should be considered for refractory cases. Retransplantation after renal allograft loss to PVAN remains a treatment option for patients clearing polyomavirus replication.
Hirsch
Hans H
HH
Transplantation Virology, Institute for Medical Microbiology and Div. Infectious Diseases, Universitätsspital Basel, Switzerland. Hans.Hirsch@unibas.ch
Brennan
Daniel C
DC
Drachenberg
Cinthia B
CB
Ginevri
Fabrizio
F
Gordon
Jennifer
J
Limaye
Ajit P
AP
Mihatsch
Michael J
MJ
Nickeleit
Volker
V
Ramos
Emilio
E
Randhawa
Parmjeet
P
Shapiro
Ron
R
Steiger
Juerg
J
Suthanthiran
Manikkam
M
Trofe
Jennifer
J
D006801:Humans; D007674:Kidney Diseases / Q000453:epidemiology / Q000601:surgery* / Q000628:therapy / Q000821:virology*; D016030:Kidney Transplantation; D027601:Polyomavirus Infections / Q000150:complications* / Q000175:diagnosis; D012307:Risk Factors