Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: a prospective evaluation.
BACKGROUND
JC virus (JCV) viruria is more common than BK virus (BKV) viruria in healthy individuals but in kidney transplants (KT), polyomavirus nephropathy (PVAN) is primarily caused by BKV. Few cases of PVAN have been attributed to JCV. Systematic studies on JCV replication in KT are lacking.


METHODS
Out of a cohort of KT patients screened with urine cytology, patients shedding decoy cells were studied (n=103). Molecular studies demonstrated BKV, JCV, or BKV+JCV shedding in 58 (56.3%), 28 (27.2%), and 17 (16.5%), respectively. Biopsy was performed when decoy cells persisted 2 months or serum creatinine increased >20%.


RESULTS
BKV viruria was strongly associated with BKV viremia (93%), PVAN (48%, P=0.01) and graft loss (P=0.03). Higher BKV viremia correlated with graft dysfunction (P=0.01), more advanced histological pattern of PVAN (P<0.0001), and more infected cells in biopsy (P=0.0001). BKV viremia of > or =10,000 copies/mL was significantly associated with histologically confirmed PVAN (P=0.0001). Reduction of immunosuppression lead to disappearance of decoy cells in patients shedding BK (>93%). JCV viruria, was more often asymptomatic (P=0.002) and affected older patients (P=0.02). JCV PVAN was less common (21.4%) and was characterized by sparse cytopathic changes but significant inflammation and fibrosis. JCV viremia was rare (14.2%), transient, and low (mean 2.0E+03/mL). After reduction of immunosuppression decoy cells persisted in >50% of patients with JCV (P=0.0001), but no graft loss occurred. During the period of the current study, the incidence of BKV-PVAN was 5.5% and the incidence of JCV-PVAN was 0.9%.


CONCLUSIONS
The data point to significant differences of BKV and JCV biology regarding replication and disease in KT patients, with important implications for screening and management.
Drachenberg
Cinthia B
CB
Department of Pathology, Medicine and Pediatrics, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
Hirsch
Hans H
HH
Papadimitriou
John C
JC
Gosert
Rainer
R
Wali
Ravinder K
RK
Munivenkatappa
Raghava
R
Nogueira
Joseph
J
Cangro
Charles B
CB
Haririan
Abdolreza
A
Mendley
Susan
S
Ramos
Emilio
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001739:BK Virus / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D001706:Biopsy; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D015994:Incidence; D007577:JC Virus / Q000235:genetics / Q000502:physiology*; D007668:Kidney / Q000473:pathology / Q000821:virology; D007674:Kidney Diseases / Q000473:pathology* / Q000821:virology*; D016030:Kidney Transplantation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D027601:Polyomavirus Infections / Q000473:pathology; D011446:Prospective Studies; D014412:Tumor Virus Infections / Q000473:pathology; D014779:Virus Replication / Q000502:physiology*
D004279:DNA, Viral