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%). CONCLUSION: 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.
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%). CONCLUSION: 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.
Authors: H T Banks; Shuhua Hu; Kathryn Link; Eric S Rosenberg; Sheila Mitsuma; Lauren Rosario Journal: Inverse Probl Sci Eng Date: 2015-03-13 Impact factor: 1.950
Authors: Liise K Kayler; Ibrahim Batal; Ravi Mohanka; Claire Morgan; Amit Basu; Ron Shapiro; Parmjeet S Randhawa Journal: Transplantation Date: 2008-09-27 Impact factor: 4.939
Authors: Rainer Gosert; Christine H Rinaldo; Georg A Funk; Adrian Egli; Emilio Ramos; Cinthia B Drachenberg; Hans H Hirsch Journal: J Exp Med Date: 2008-03-17 Impact factor: 14.307
Authors: H H Hirsch; F Vincenti; S Friman; M Tuncer; F Citterio; A Wiecek; E H Scheuermann; M Klinger; G Russ; M D Pescovitz; H Prestele Journal: Am J Transplant Date: 2012-11-08 Impact factor: 8.086