Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection.
BACKGROUND
Mycophenolate Mofetil (MMF) has been shown to significantly decrease the number of acute rejection episodes in renal transplant recipients during the 1st year. A beneficial effect of MMF on long-term graft survival has been more difficult to demonstrate. This beneficial effect has not been detected, despite the impact of acute rejection on the development of chronic allograft nephropathy and experimental evidence that MMF may have a salutary effect on chronic allograft nephropathy independent of that of rejection.


METHODS
Data on 66,774 renal transplant recipients from the U.S. renal transplant scientific registry were analyzed. Patients who received a solitary renal transplant between October 1, 1988 and June 30, 1997 were studied. The Cox proportional hazard regression was used to estimate relevant risk factors. Kaplan-Meier analysis was performed for censored graft survival.


RESULTS
MMF decreased the relative risk for development of chronic allograft failure (CAF) by 27% (risk ratio [RR] 0.73, P<0.001). This effect was independent of its outcome on acute rejection. Censored graft survival using MMF versus azathioprine was significantly improved by Kaplan-Meier analysis at 4 years (85.61% v. 81.9%). The effect of an acute rejection episode on the risk of developing CAF seems to be increasing over time (RR=1.9, 1988-91; RR=2.9, 1992-94; RR=3.7, 1995-97).


CONCLUSIONS
MMF therapy decreases the risk of developing CAF. This improvement is only partly caused by the decrease in the incidence of acute rejection observed with MMF; but, is also caused by an effect independent of acute rejection.
Ojo
A O
AO
Department of Medicine, The University of Michigan, Ann Arbor 48109, USA.
Meier-Kriesche
H U
HU
Hanson
J A
JA
Leichtman
A B
AB
Cibrik
D
D
Magee
J C
JC
Wolfe
R A
RA
Agodoa
L Y
LY
Kaplan
B
B
D000208:Acute Disease; D001379:Azathioprine / Q000627:therapeutic use; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine