Efficacy and safety of universal valganciclovir prophylaxis combined with a tacrolimus/mycophenolate-based regimen in kidney transplantation.
BACKGROUND
Immunosuppressive and antiviral prophylactic drugs are needed to prevent acute rejection and infection after transplantation. We assessed the efficacy and safety of the introduction of universal valganciclovir prophylaxis in combination with a tacrolimus/mycophenolate-based regimen in kidney transplantation at our centre.


METHODS
We reviewed all consecutive patients who underwent kidney transplantation over a 5.5-year period. Patients transplanted from January 2000 to March 2003 (period 1) were compared to patients from April 2003 to July 2005 (period 2). In period 1 patients were treated with basiliximab, cyclosporine, steroids and mycophenolate (or azathioprine). Prophylaxis with valacyclovir was prescribed in cytomegalovirus (CMV) D+/R- patients, while any R+ patients were managed with a preemptive approach. In period 2, immunosuppression consisted of basiliximab or thymoglobulin induction, tacrolimus, steroids and mycophenolate. Three-month CMV prophylaxis with valganciclovir was used in all at-risk patients.


RESULTS
Data analysis included 73 patients (period 1) and 70 (period 2). Acute rejection was more frequent in period 1 than in period 2 (42% vs 7%, p <0.001). Overall, 30% of patients in period 1 were diagnosed with CMV infection/disease requiring antiviral treatment, compared with 11.4% in period 2 (p = 0.003). Late-onset CMV disease remained a problem in D+/R- patients in both periods. There was no difference in incidence of BK virus nephropathy, fungal infections, PTLD, graft loss or mortality. However, 4 cases (5.7%) of delayed transient asymptomatic agranulocytosis were observed in period 2.


CONCLUSIONS
The present analysis indicates that the combined regimen introduced in period 2 improved clinical results with a significant decrease in acute rejection and in CMV infection/disease incidence. However, a unique syndrome of delayed transient agranulocytosis probably due to drug myelotoxicity was observed in a subset of patients.
Transplantation Centre, Centre Hospitalier Universitaire Vaudois, University Hospital of Lausanne, CH-1011 Lausanne, Switzerland.
Oriol
O
Manuel
Jean-Pierre
JP
Venetz
Jacques
J
Fellay
Jean-Blaise
JB
Wasserfallen
Nada
N
Sturzenegger
Massimiliano
M
Fontana
Maurice
M
Matter
Pascal R
PR
Meylan
Manuel
M
Pascual
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000187:drug effects; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008485:Medical Audit; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care; D012189:Retrospective Studies; D012449:Safety; D013557:Switzerland; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D000077562:Valganciclovir
D000903:Antibiotics, Antineoplastic; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D000077562:Valganciclovir; D009173:Mycophenolic Acid; D015774:Ganciclovir; D016559:Tacrolimus