Reduction by combination prophylactic therapy with CMV hyperimmune globulin and acyclovir of the risk of primary CMV disease in renal transplant recipients.
CMV-seronegative recipients of kidneys from CMV-seropositive donors (D+/R+) are at highest risk for developing clinical CMV disease. Even with routine prophylactic use of low-dose acyclovir we had a CMV disease incidence of 26% (5/19) in these patients. Published studies using either acyclovir or CMV hyperimmune globulin (HIG) alone as prophylaxis have also shown clinical disease in 20-30% of D+/R+ patients--less than controls but still significantly greater than in comparable CMV+ recipients (R+). The purpose of this study was to determine whether the risk of primary CMV disease in D+/R- patients was reduced by prophylaxis with combined CMV-HIG and low-dose acyclovir as follows: CMV-HIG (Immuno) 1 ml/kg i.v. immediately prior to transplantation and at 3-week intervals for 6 months; acyclovir 600 mg/day p.o. for 3 months. A total of 361 consecutive renal transplants were studied prospectively. All D+/R- pts (n = 73) received CMV-HIG and acyclovir, the others (91 D+/R+, 74 D-/R+, 123 D-/R-) received only low-dose acyclovir. The incidence of clinical CMV disease, CMV-related graft loss, graft and patient survival, and the influence of ALG and OKT-3 were analyzed and compared between groups. Of the 361 patients only 18 (5%) developed CMV disease, with 5 CMV-related graft losses. CMV disease occurred in only 10% of the D+/R- patients, lower than in previously reported studies. Significantly the incidence was as low as in CMV+ recipients of kidneys from both CMV+ (6%) and CMV- (7%) donors. Use of OKT-3 for steroid-resistant rejection increased the risk of developing CMV disease: 11/50 (22%) receiving OKT-3 developed CMV disease vs. only 7/311 (2%) who did not (P < 0.001); 11/18 (61%) with CMV disease had received OKT-3. ALG induction immunosuppression did not increase the risk of CMV in patients who subsequently received OKT-3. No patient developed CMV disease after discontinuing prophylaxis. There were no complications related to either CMV-HIG or acyclovir use. Compared with all other patients, the D+/R- group had superior graft survival at 1 and 3 years (94% vs. 87% and 86% vs. 74%, P < 0.05) but similar patient survival. Combined CMV-HIG and low-dose acyclovir appear to be better than either agent alone in preventing primary CMV disease in CMV- patients who receive CMV+ kidneys. Low-dose oral acyclovir (600 mg/day) may be as effective in preventing CMV disease as higher-dose prophylactic regimens, at least when accompanied by CMV-HIG.(ABSTRACT TRUNCATED AT 400 WORDS)
Kidney Transplant Service, Victoria General Hospital, Halifax, Nova Scotia, Canada.
D L
DL
Nicol
A S
AS
MacDonald
P
P
Belitsky
S
S
Lee
A D
AD
Cohen
H
H
Bitter-Suermann
J
J
Lowen
A
A
Whalen
D000212:Acyclovir / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D006085:Graft Survival; D006801:Humans; D007116:Immunization, Passive; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D007223:Infant; D007231:Infant, Newborn; D016030:Kidney Transplantation / Q000009:adverse effects; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use; D014019:Tissue Donors
D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D016853:Muromonab-CD3; C045781:cytomegalovirus-specific hyperimmune globulin; D000212:Acyclovir