Prophylaxis against Herpes Infections in Kidney Transplant Patients with Special Emphasis on CMV

Abstract

Method: Since 1990, we have treated all kidney transplanted patients with cyclosporin (CsA)+ an initial 10 d anti-lymphocyte globulin (ALG) course, from September 1995 supplemented with mycophenolate mofetil (MMF). In 170 consecutive transplantations from June 1992 to the end of 1996, aciclovir 3200 mg/d (adjusted for kidney function and in children to age) was given prophylactically for 3 months post-transplantation (Tx), monitored with systematic and frequent tests for HSV and CMV. In case of CMV infection, we gave ganciclovir intravenously (oral ganciclovir from 1996) in doses according to kidney function for 3 months, followed by a further 3 months observation and monitoring period. In case of acute cellular rejection, ganciclovir was given during the 10-d OKT3 course and 1 week further. In case of delayed graft function combined with aciclovir side effects, ganciclovir was given until aciclovir could be reintroduced. Results: 39% were HSV seronegative at Tx. There were no seroconversions or reactivations within the observation period. No mucocutaneous HSV infections was observed. No resistant strains developed. 26% were both HSV and CMV negative at Tx. 52% were CMV negative at Tx. 30% experienced a CMV infection post-transplant. The patients were grouped according to CMV status in the donor (D) and recipient (R) before Tx. We found approximately the same number of patients in the 4 CMV groups D-/R-, D+/R-, D-/R+ and D+/R+. Most infections occurred in the D+/R- group compared to D-/R- (p=0.009). A significant increase in the number of CMV infections occurred in this subgroup when we gave reduced doses in case of delayed graft function (p=0.015), from 1994. We observed only 1 CMV disease (in 1992). Serological EBV testing were performed concomitantly. No correlation was seen between CMV and EBV infections. From September 1995 we have treated all transplanted patients (n=40) with CsA/ALG/MMF. We found no significant increase in CMV infections in this group. Conclusions: Prophylaxis with aciclovir (combined with ganciclovir during acute rejections and in case of delayed graft function with aciclovir side effects) gives a good protection against HSV and CMV infections and prevents CMV disease effectively. High-dose aciclovir post-transplantation (or shift to ganciclovir) seems to be important to obtain effective prophylaxis. Better immunosuppression with MMF does not result in more CMV infections.