LATE BREAKING II

O. Witzke¹, M. Nitschke², M. Bartels³, U. Ott⁴, I.A. Hauser^5
1Department Of Nephrology, University Hospital Essen, Essen/GERMANY, ²Devision Of Nephrology And Transplantation, University of Lübeck, Lübeck/GERMANY, ³Surgical Clinic, University Hospital Leipzig, Leipzig/GERMANY, ⁴Internal Medicine Iii, Friedich-Schiller-University, Jena/GERMANY, ⁵Nephrology, University Hospital Frankfurt/M, Frankfurt/M/GERMANY

Body: Introduction: Prophylaxis and preemptive therapy are competitive approaches to prevent cytomegalovirus (CMV) infection after renal transplantation. Several prospective randomized studies show that in high risk (D+/R-) patients prophylaxis is the best option for preventing CMV, and to a lesser extend this is also true for D+/R+ patients. Within the last few years, evidence is growing that not only CMV disease but also asymptomatic (subclinical) active CMV infection correlates with increased long term morbidity, graft loss, diabetes, atherosclerosis and mortality following solid organ transplantation. Methods: We performed a randomized clinical trial to determine if renal transplant recipients with a positive CMV serostatus had a higher rate of active CMV infection (i.e. CMV replication) and disease when treated preemptively for CMV infection, compared to recipients treated with primary prophylaxis; and whether this correlates with a higher rate of chronic graft alteration and long-term graft and patient survival. Prophylaxis consisted of 2x450mg (900mg) valganciclovir tablets/day adjusted for renal function for 100 days post-transplantation. Patients were monitored with a quantitative CMV PCR test (Cobas^â Amplicor^â CMV-Monitor) and positive patients (≥ 400 CMV DNA copies/ml) received 4 valganciclovir tablets 1800mg/day adjusted for renal function followed by secondary prophylaxis with 2 valganciclovir tablets 900mg/day for 28 days. Patients were to be followed for 5 years; initial 12 month data are presented in this abstract. Results: 296 patients were analyzed (168 D+/R+ and 128 D-/R+), 146 to prophylaxis and 150 to preemptive therapy. At 12 months overall tolerability was good for both treatments. Episodes of acute graft rejection were more common with prophylaxis (18.5% versus 12.0%, p>0.05, prophylaxis versus preemptive therapy), but a significantly higher rate of rejection was only observed in the D-/R+ group (21.4% versus 8.3%, p=0.042, prophylaxis versus preemptive therapy), with no difference in the D+/R+ group (16.7% versus 15.4%, p>0.05, prophylaxis versus preemptive therapy). Active CMV infection was significantly higher with preemptive therapy (36.0% versus 10.3%, p<0.0001, preemptive therapy versus prophylaxis), and most CMV infection was seen for D+/R+ patients receiving preemptive therapy (51.3% versus 14.4%, p<0.0001, preemptive therapy versus prophylaxis). Similarly, D+/R+ patients with preemptive therapy had the greatest rate of CMV disease (19.2% versus 4.4%, p=0.003, preemptive therapy versus prophylaxis). Renal function was similar for prophylaxis versus preemptive therapy. Graft loss occurred for more preemptive patients (4.7% versus 2.7%, p>0.05, preemptive therapy versus prophylaxis). Conclusion: In conclusion, valganciclovir prophylaxis significantly reduces the incidence of CMV infection and disease, particularly for D+/R+ patients without reducing overall graft function. Hence, the antiviral effect of CMV prophylaxis may be dependent on the CMV status of the donor and routine prophylaxis for all D+/R+ patients should be considered. The ongoing follow-up will determine if additional long-term benefits for graft survival are observed for D+/R+ patients receiving prophylaxis.

Disclosure: All authors have declared no conflicts of interest.