Prophylaxis of Cytomegalovirus Primary Infection With Short-Term
Ganciclovir Theraphy
R. Lauzurica, B. Baye ´s, C. Frı´as, A. Herna ´ ndez, A. Jimenez, N. Fontsere ´ , and R. Romero
C
YTOMEGALOVIRUS (CMV) remains one of the
most important pathogens in kidney and other solid
organ transplantation. It produces greater morbility nowa-
days rather than the significant mortality rates in the past.
CMV not only produces direct damage due to the infection,
but also indirect complications including excessive immu-
nosuppression and augmented acute rejection as well as
decreasing patient and allograft survivals and increasing
economic costs.
1
The most important risk factors for CMV
infection are recipient CMV serologic status in relation to
organ donor serology (D
+
/R
-
), and the use of antilympho-
cyte antibodies either for induction or for acute rejection
therapy.
1,2
There are two major forms of CMV infection;
prophylaxis by administration of antiviral drugs or gamma-
globulins at the time of transplantation and for a variable
period after transplantation, and preemptive therapy,
namely giving antiviral drugs when there is evidence of the
virus replication after kidney transplantation.
1,3
We report our experience with a group of high risk
patients (D
+
/R
-
) who received low-dose and short-term
gancyclovir prophylaxis.
PATIENTS AND METHODS
Definitions
Between July 1997 and July 2002, 156 kidney transplants were
performed at our Kidney Transplantation Unit. Fifteen seronega-
tive recipients received a kidney allograft from a seropositive
donor. Prophylaxis included intravenous (IV) gancyclovir (1.25–5
mg/kg/d adjusted by kidney function) for 1 week, followed by oral
(PO) gancyclovir (500 mg/8 –12 hours according to the body mass
index) for 3 more weeks (total treatment period of 4 weeks). The
diagnosis of CMV infection was established by seroconversion
and/or pp65 antigenemia.
Asymptomatic CMV infection was diagnosed when evidence of
seroconversion and/or positive antigenemia occurred without any
clinical features. Symptomatic CMV infection occurred when se-
roconversion and/or positive antigenemia were associated with
fever and/or leukopenia without organ or tissue involvement. CMV
disease was established when there was evidence of CMV infection
with involvement of one or more organs.
RESULTS
Fourteen of the 15 patients were men. Mean age was 41
years (range 19 – 69). Only 2 received induction with anti-
lymphocyte antibodies; all received prednisone; 12 tacroli-
mus; 3 cyclosporine; 11 mycophenolate mofetil; and 3
azathioprine. Two experienced an acute rejection episode
that was treated (and resolved) with methylprednisolone
pulses (250 –500 mg IV for 3 days). Thirteen of 15 devel-
oped a primary infection; two (2 and 25 months after KT)
have not seroconverted yet. CMV diagnosis was established
between 3 and 78 days after KT (mean 48 days). Asymp-
tomatic CMV infection was detected in two patients who
did not receive therapy. Symptomatic infection occurred in
seven patients with CMV disease in four patients, including
(mild transaminitis in three; and only one patient with
transaminitis, pneumonitis and superinfection) with Pneu-
mocystis carinii. In 12 patients, diagnosis was achieved by
positive antigenemia and in 1 by seroconversion. Only three
patients required hospital admission (for 2, 10, and 30 days,
respectively). In all but one subject therapy consisted of
ganciclovir (PO 500 mg/3 times a day for 1 month). In two
patients with CMV disease, ganciclovir was initiated IV
followed by PO delivery and in one (with pneumonitis) was
combined with specific gammaglobulin. There were no
deaths. Neither infection recurrences nor drug resistances
occurred. Up to now all patients but one have functional
kidneys (serum creatinine below 140 mol/L) without clin-
ical, biological, or histologic criteria of chronic allograft
nephropathy. One patient lost the kidney due to active
alcoholism after kidney transplantation with noncompli-
ance to immunosuppresion medications.
DISCUSSION
Strategies for CMV infection prophylaxis are diverse: CMV
hyperimmune globulins, which are more effective than
unselected globulin treatment, acyclovir, valacyclovir, and
ganciclovir.
1,4
The best results have been obtained with
ganciclovir but the doses and lengths of treatment are quite
different from those described in our protocol.
1,4,5
The
From the Nephrology Department, Kidney Transplant Unit
(R.L., B.B., N.F., R.R.) and Microbiology Department (C.F., A.H.,
A.J.), Hospital Universitari Germans Trias i Pujol, Badalona,
Spain.
Address reprint requests to Dr Ricardo Lauzurica, Kidney
Transplant Unit, Hospital Universitari Germans Trias i Pujol,
Crta.del Canyet, s/n -08916 Badalona, Spain. E-mail:
rlauzu@ns.hugtip.scs.es
© 2003 by Elsevier Inc. All rights reserved. 0041-1345/03/$–see front matter
360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/s0041-1345(03)00714-0
Transplantation Proceedings, 35, 1751–1752 (2003) 1751