CMV disease in CMV-mismatched renal transplant recipients with prophylactic low dose valaciclovir

Valaciclovir (VACV) 2 g q.i.d. for 3 months after kidney transplantation has been shown, (Lowance et al., NEJM 1999; 340: 1462-70), to reduce CMV disease from 45 to 16% and rejection from 52 to 26% in CMV-negative (D+R-) recipients. Neurotoxic side effects, however, were frequent, and 5% of the patients experienced hallucinations. We hypothesised that a lower dosage of VACV would prevent CMV disease with fewer CNS side effects.

Since September 1998 all CMV-mismatched renal transplant recipients received VACV 1 g t.i.d. for 3 months posttransplantation (PT). The incidence of CMV disease, rejection and neurotoxic side effects during 6 months PT was studied retrospectively in, up to now, 25 patients.

24% (6/25) of the patients developed CMV disease. The mean time for onset of symptoms was 145 days (92-191). Five of the patients had mild-moderate symptoms and recovered after ganciclovir therapy for 3 weeks. One patient was diagnosed with a CMV-associated retinitis on day 191 PT. The rate of biopsy-confirmed acute graft rejection was 32% (8/25). 20% (5/25) of the patients had a serum creatinine of >200 micromol/l after 6 months, including one patient on hemodialysis. CNS adverse effects were not observed. None out of nine patients with basiliximab induction and VACV developed CMV disease. One patient with basiliximab that did not receive VACV, developed a symptomatic CMV-infection.

The incidence of CMV disease was lower than in historical controls at our centre, and the time to onset of symptoms was prolonged. Compared to the 8 g VACV/day study, CMV disease and graft rejection was more frequent, but no neurotoxic side effects were observed. A combination with basiliximab induction and VACV 3 g/day shows promising results, but randomised studies are needed for confirmation.