Cytomegalovirus-specific immune monitoring to guide pre-emptive therapy surveillance protocol for prevention of cytomegalovirus infection after renal transplantation.

QuantiFERON-CMV assay at 3 weeks after transplatation, based on the result: 1) QuantiFERON-CMV positive recipients: monitoring for cytomegalovirus (CMV) DNAemia detection using quantitative real-time PCR from whole blood once a week for 4 weeks and subsequently, at months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, and 24. For safety reasons and for equal probability to detect all episodes of CMV DNAemia, PCR CMV be evaluated at weekly intervals up to Month 4 post-transplantation similarly as in the control group. PCR CMV once a week will be likewise performed during pre-emptive valganciclovir therapy or treatment of CMV disease. In cases of antirejection therapy with methylprednisolone pulses or lymphocyte depleting antibodies (antithymocyte globuline or rituximab) and/or treatment of antibody-medaited rejection (plasmapheresis, immunoadsorption, IVIG, bortezomib) a new Quantiferon-CMV evaluation will be performed 1 week after antirejection therapy initiation. If Quantiferon-CMV positive result persists at least one single PCR CMV test will be performed 1 month after antirejection therapy initiation. In the case of negative or indeterminate QuantiFERON-CMV result weekly PCR CMV monitoring will be started and continued up to Months 4 post-transplantation or for 1 month in later post-transplantation period. Similarly, QuantiFERON-CMV will be reassessed at the end of pre-emptive valganciclovir therapy or therapy of CMV disease. In the case of negative or indeterminate QuantiFERON-CMV result a switch to weekly PCR CMV monitoring will be started and continued up to Month 4 after transplantation. In all QuantiFERON-CMV positive patients with CMV viral load of more than 1000 IU/mL detected at sheduled time points, pre-emtive therapy with valganciclovir (Valcyte; Hoffman-La Roche, Grenzach-Wyhlen, Germany) will be instituted at a dose of 900 mg twice daily with food within 7 days at the latest and continued until reaching clearance of CMV DNAmia in 2 consecutive measurements (<50 IU/mL, at least for 14 days). 2) QuantiFERON-CMV negative/inderminated recipients: same weekly PCR CMV monitoring as in the control group including the same schedule of QuantiFERON-CMV assessments. Weekly PCR CMV monitoring up to Month 4 will be maintained irrespective to the change of QuantiFERON-CMV result in later post-transplant period.. Pre-emptive oral valganciclovir (VALCYTE; Roche) therapy at a dose of 900 mg twice daily if CMV viral load exceeds 1000 IU/mL. Pre-emptive valganciclovir will be started within 7 days and continued until reaching clearance of CMV DNAmia in 2 consecutive measurements (<50 IU/mL, at least for 14 days).