Rapid dynamics of polyomavirus type BK in renal transplant recipients.
BACKGROUND
Polyomavirus type BK-associated nephropathy (PVAN) is an emerging cause of early renal transplant failure. No specific antiviral treatment has been established. Current interventions rely on improving immune functions by reducing immunosuppression. In patients with PVAN, a high BK virus (BKV) load is detectable in plasma. However, the relationship between BKV replication and disease is not well understood.


METHODS
In a retrospective analysis of BKV plasma load in renal transplant recipients undergoing allograft nephrectomy (n = 3) or changes in immunosuppressive regimen (n = 12), we calculated viral clearance rates and generation times and estimated the loss of BKV-infected renal cells.


RESULTS
After nephrectomy, BKV clearance was fast (viral half-life [t(1/2)], 1-2 h) or moderately fast (t(1/2), 20-38 h), depending on the sampling density, but it was independent of continued immunosuppressive regimens. After changing immunosuppressive regimens, BKV was cleared with a t(1/2) of 6 h-17 days. Using the basic reproductive ratio, the efficacies of intervention ranged from 7% to 83% (mean, 28%; median, 22%).


CONCLUSIONS
The results emphasize that high-level BKV replication is a major pathogenetic factor that may have implications for genome rearrangements, immune evasion, and antiviral resistance.
Funk
Georg A
GA
School of Biological Sciences, Royal Holloway University of London, Egham, UK.
Steiger
Jurg
J
Hirsch
Hans H
HH
D001739:BK Virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects*; D008954:Models, Biological; D009392:Nephrectomy; D027601:Polyomavirus Infections / Q000821:virology*; D012189:Retrospective Studies; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication
D007166:Immunosuppressive Agents