INTRODUCTION

Cytomegalovirus (CMV) infection is one of the main causes of morbi-mortality in renal transplant patients (1,2). Different behaviour and treatment regimes exist to prevent it, from the prevention of the primary infection avoiding CMV+ donor with CMV- recipient to the use of prophylactic treatments with oral acyclovir (3), endovenous gancyclovir (4), specific anti-CMV gammaglobulin (5) etc. In our case, we set out our experience with preemptive treatment of the CMV infection. We carried out a prospective study of the use of antigenemia with the pp65 as a marker which identifies the patients at risk of suffering from cytomegalovirus disease and which allows the establishment of preemptive treatment with gancyclovir.

Material and methods: The study covers 79 renal transplant patients in our centre between September 1998 and September 1999. The mean age of the same was 59 years. The immunosuppression used was quadruple sequential with polyclonal SAL (Timoglobulina^® 1.25 mg/kg/day) for 5-7 days, anticalcineurinic (cyclosporine 9 mg/kg/day or tacrolimus 0.1 mg/kg/12 hours), mycophenolate mofetil (1-2 gr/day 6 months) and prednisone.

Samples were taken of total blood (antigenemia for pp65) and of urine (viruria) weekly between weeks 4 and 12 after transplantation. All the patients with positive antigenemia and without criteria of disease were treated with ev gancyclovir for 3 days followed by treatment with oral gancyclovir for a further 11 days.

In the event of suffering from disease they were treated with ev gancyclovir for 14 days. The infection and disease index is expressed on table I in accordance with serology for CMV of donor (D) and recipient (R). The patients with positive viruria and negative antigenemia were not treated.

Results:

As with most studies on this subject, we observed that the D-/R- combination is not frequent (2.5 %) and does not entail any risk of suffering from CMV infection or disease (0%). No prophylactic treatment or serialized antigenemia should be carried out in this small group of patients.

It was moreover confirmed that the D+/R- group has an extremely high risk of suffering from a primary infection (67 %), and in these primarily infected patients preemptive treatment with gancyclovir is not useful to prevent the appearance of disease, as 100% of the primarily infected patients develop it and mostly in a serious form. Despite this development, no patient died as a result of the same.

In this D+/R- group, prophylactic treatment should be initiated from the time of transplantation. The most frequent group was the D+/R+ (81 %), 31 % of this group presenting positive antigenemia. Of the patients who presented it, 60 % presented CMV disease, although mostly slight or moderate. Surprisingly, the D-/R+ group presented 0 % of positive antigenemia and no cases of disease, it being deduced that reinfection by the donor would appear to be more important for the development of disease than reactivation by the recipient.

In relation to preemptive treatment of patients who had + antigenemia without criteria of disease, ev gancyclovir followed by oral gancyclovir was shown to be effective, it not being necessary in any case to change from oral gancyclovir to ev gancyclovir due to lack of therapeutic response. No patient with positive viruria and negative antigenemia developed the disease. Viruria was not of predictive use in any of the serological groups.

Conclusions:

1/ The use of antigenemia associated with strict clinical control allows an early diagnosis and preemptive treatment of CMV infection in the renal transplant patient.

2/ D+/R- is shown to be a high-risk serological group. In this group, prophylactic treatment with gancyclovir should be initiated on beginning the transplantation.

3/ Ev gancyclovir followed by oral gancyclovir is effective in the treatment of CMV infection, not being associated with an increase in relapses.

4/ With post-transplantation CMV infection, reinfection by the donor would appear to be more important that the reactivation of the recipient’s CMV.

5/ Viruria was not of predictive use in any of the serological groups.

REFERENCES

1- "Infectious disease complications of renal transplantation" Rubin RH. Kidney Int 44: 221, 1993.

2- "Management and prevention of cytomegalovirus infection after renal transplantation" Farrugia E, Schwab TR. Mayo Clin Proc 67: 879, 1992.

3- "A randomized, placebo-controlled trial of oral acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts" Balfour HH Jr, Chace BA, Stapleton JT et al. N Engl J Med 320: 1381, 1989.

4- "New developments in cytomegalovirus prevention and management" Snydman DR, Rubin RH, Werner BG. Am Kidney Dis 21: 217, 1993.

5- "Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal transplant recipients" Snydman DR, Werner BG, Heinze-Lacey B et al. N Engl J Med 317: 1049, 1987.