Cytomegalovirus risk factors in renal transplantation with modern immunosuppression.
BACKGROUND
Immunosuppressive regimens have lowered the rate of kidney rejection, but with increasing immunodeficiency-related complications. New cytomegalovirus (CMV) prophylaxis also has become available. The impact of these 2 developments on CMV diseases has not been well evaluated. We conducted a randomized trial comparing a drug regimen common in the 1980s, cyclosporin A (CsA) with azathioprine (Aza), with a drug combination used most today, tacrolimus (Tac) with mycophenolate mofetil (MMF), and we analyzed CMV risk factors in kidney transplant patients.


METHODS
The 300 patients included in the trial underwent the same universal prophylaxis and preemptive therapy. CMV events and risk factors were prospectively recorded.


RESULTS
With preventive and preemptive strategies combined for 3 months, CMV replication was detected in 32.6% and CMV disease in 18.1% of patients. Multivariate analysis on risk factors for CMV disease were CMV donor (D)/recipient (R) matching and first month renal function (risk ratio [95% confidence interval]: 1.02 [1.01; 1.04]; P=0.011), but not the immunosuppressive regimen (P=0.35). The D+/R- combination increased the risk of CMV disease by a factor of 9 (P<0.0001) when compared with D-/R- status, and a factor of 3.5 (P<0.0001) when compared with all CMV-positive recipients. Despite the 50% rate of CMV disease in the D+/R- group, no asymptomatic CMV replication was detected with the preemptive strategy.


CONCLUSIONS
With modern immunosuppression, a sequential quadritherapy with Tac/MMF, and a 3-month CMV prevention strategy, the risk for CMV disease remains close to that with CsA/Aza. A CMV-negative recipient transplanted from a CMV-positive donor (D+/R-) remains a major risk factor, calling for better CMV prophylaxis or matching in negative recipients. Preemptive strategy thus appeared inefficient for this high-risk group. Transplant recipients with altered renal function should also be considered at risk.
Bataille
S
S
Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, AP-HM, Marseille, France.
Moal
V
V
Gaudart
J
J
Indreies
M
M
Purgus
R
R
Dussol
B
B
Zandotti
C
C
Berland
Y
Y
Vacher-Coponat
H
H
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D018890:Chemoprevention; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000187:drug effects / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000453:epidemiology* / Q000517:prevention & control* / Q000821:virology; D004359:Drug Therapy, Combination; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D051437:Renal Insufficiency; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine; D015774:Ganciclovir; D016559:Tacrolimus