84 Predictive risk factors of post-transplant high-grade CMV reactivation in CMV-seropositive patients in the modern immunosuppressive era

Abstract

INTRODUCTION AND OBJECTIVES: Cytomegalovirus (CMV) prophylaxis is recommended for CMV-seronegative kidney transplant recipients (R-) receiving the grafts from CMV seropositive donors (Dþ). Meanwhile, whether Rþ patients need universal CMVprophylaxis remains unclear. Most of Rþ patients with low-grade CMV reactivation show spontaneous remissionwithout deteriorating thegraft function and survival. In addition, valganciclovir (VGCV) possibly causes some adverse effects and GCVresistant CMV. Although targeting CMV prophylaxis to Rþ patients is ideal, there are few reports addressing the risk factors of highgrade CMV reactivation in Rþ patients in the modern immunosuppressive era. METHODS: Since July 2004, consecutive 151 Rþ patients who received the kidney from Dþ in our hospital were enrolled in this study. No recipients received CMV prophylaxis. The induction immunosuppressive therapy was consisted of tacrolimus, MMF, steroid, and basiliximab. Patients with immunological high risks (ABO-incompatible or donor specific anti-HLAantibody positive) received a single-low dose of rituximab and 3 to 4 sessions of apheresis prior to transplantation. High-grade CMV reactivation was defined as CMV-antigenemia (Ag) positive cells becoming higher than 10/200,000 blood leukocytes during the clinical course. The CMV-Ag levelwasmonitoredat2 to3-weekly intervalsuntil 6months,andat monthly intervals from6 to 12months post-transplantation.We investigated the predictive risk factors of high-grade CMV reactivation in Rþ patients. RESULTS: The proportion of high-grade CMV reactivation was 29.8% (45/151) in this series. All patients who developedCMV reactivation were cured by VGCV or GCV successfully without inducing GCV-resistant CMV. Although no significant difference was found in the graft function, the graft survival was significantly shorter in the Rþ patients with CMV reactivation than those without (p 1⁄4 0.019). In multivariate analysis, the pre-transplant low-IgG titer against CMV (p 1⁄4 0.014), potent immunosuppressive protocol (p 1⁄4 0.019), and high level of MPA AUC 0-12 at 1 month after transplantation (p 1⁄4 0.045) were independently associated with the development of high-grade CMV reactivation in Rþ patients. CONCLUSIONS: The development of high-grade CMV reactivation deteriorated the graft survival in Rþ patients in the modern immunosuppressive era. Pre-transplant low-IgG titer against CMV, potent immunosuppressive protocol, and high MPA level were predictive risk factors for the development of high-grade CMV reactivation.