Does mycophenolate mofetil increase the incidence of cytomegalovirus disease compared with azathioprine after cadaveric kidney transplantation?
Although most of the published papers had not found increase in the incidence of CMV disease in kidney transplant recipients treated with mycophenolate mofetil (MMF), we had feeling from everyday practice that after its introduction number of patients with CMV disease has increased. To test this hypothesis, we performed retrospective analysis of our database, comparing the incidence of CMV disease in patients treated with azathioprine (AZA) and patients treated with MMF. CMV disease was defined as CMV antigenemia (positive CMV pp65 determined by ELISA test) plus any of the following: decrease leucocytes or platelets, increased transaminases, increase in serum creatinine. The azathioprine treated group (AZA group) included 280 patients (132 female) treated for 17,672 months with AZA + Cyclosporine A (CyA) + steroid, or AZA + steroid, while the MMF group included 219 patients (112 female) treated for 5079 months with MMF + CyA + steroid, or MMF + steroid. There was no difference in acute rejection episodes between the AZA and the MMF group. The AZA group had 51 CMV disease episodes (1 episode per 346.5 treatment months), and the MMF group experienced 43 episodes (1 per 118.1 months) (P < .01). Mean onset of CMV disease was 32.65 +/- 47.69 (SD) months after transplantation in the AZA group, and 3.72 +/- 4.43 in the MMF group. There was no difference between two treatment groups regarding the donor-recipient CMV status mismatch. Despite having the increased incidence of CMV disease, MMF group had less severe disease compared to AZA group with decrease in leukocyte count in 11.6% vs 15.7% of episodes, decrease in platelet count in 20.9% vs 21.6%, elevation of transaminases in 18.6% vs 29.4% respectively, and finally increase in serum creatinine greater than 20% in 51.2% in MMF vs 74.5% in AZA group. Five patients from the AZA group experienced CMV pneumonitis with the mortality rate of 80%. Only one patient from the MMF group had CMV pneumonitis, and he survived. According to our results, patients treated with MMF have increased risk for development of CMV disease. However, the disease course is less severe, and less frequently accompanied with deterioration of renal function in comparison to the AZA group.
Basic-Jukic
N
N
Department of Dialysis, University Hospital Center Zagreb, Zagreb, Croatia. nina_basic@net.hr
Kes
P
P
Bubic-Filipi
L J
LJ
Puretic
Z
Z
Brunetta
B
B
Pasini
J
J
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001379:Azathioprine / Q000009:adverse effects*; D002102:Cadaver; D003586:Cytomegalovirus Infections / Q000139:chemically induced / Q000453:epidemiology*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D011183:Postoperative Complications / Q000453:epidemiology / Q000821:virology; D012189:Retrospective Studies; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine