Of these, BKVAN is the most common and the most clinically significant because of its association with graft loss . BKVAN was essentially a nonexistent entity in the 1980s and early 1990s, confirmed by a study that retrospectively KOS 953 Inhibitors,Modulators,Libraries reviewed biopsy slides of kidney transplant patients shedding decoy cells (cells in the urine that contain viral inclusions) between 1985 and 1996 . However, Inhibitors,Modulators,Libraries its incidence has steadily increased in the subsequent years, with reports from recent decades describing incidence rates as high as 10% . More importantly, BKVAN has emerged as an important cause of graft loss, reported in 0% to 80% of cases depending on immunosuppressive regimen employed, cohort size, timing of detection, and management strategy instituted [6, 13, 16].
Current knowledge regarding risk factors for BKVAN in the posttransplant period is extremely limited and inconsistent. A number of clinical and demographic factors have been associated with increased Inhibitors,Modulators,Libraries risk (Table 1) [17�C35], but most have been only variably implicated and have limited predictive value . More plausible is the notion that risk of BKVAN is dependent on the interaction of multiple risk factors , with a primary contribution from immunosuppression, and additional contributions from such donor, recipient, and viral factors as those tabulated. Table Inhibitors,Modulators,Libraries 1 Factors other than immunosuppression associated with increased risk of posttransplant BKV replication. 2. Immunosuppression and BKV Immunosuppression is the most significant and the only widely accepted risk factor for posttransplant BKV replication.
This is largely because BKV associated disease is seen only in immunosuppressed populations, and because multiple studies have shown reductions in BKV replication following immunosuppression minimisation . However, the relationship Inhibitors,Modulators,Libraries between BKVAN and immunosuppression remains poorly defined. Particularly, it remains unclear whether any particular agent can be specifically implicated, or whether overall potency of immunosuppression is responsible. 2.1. In Vitro Studies Surprisingly, in addition to its immunosuppressive properties, cyclosporine has been shown to possess antiviral activity in vitro against herpes simplex virus , vaccinia virus , HIV-1 [40, 41], and hepatitis C virus [42�C45].
Similarly, some studies have shown a suppressive effect of mycophenolic acid (MPA; Cilengitide the active drug moiety of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS)) on the in vitro replication of various herpes viruses , HIV-1 [47�C49], and hepatitis B virus [50�C52]. Based on these data, Acott et al. [53, 54] investigated the impact of cyclosporine and MPA on BKV replication using Vero E6 cells of green monkey origin infected with BKV (VJ isolate) when 70�C90% confluence had been reached.