A retrospective analysis of mycophenolic acid and cyclosporin concentrations with acute rejection in renal transplant recipients.
OBJECTIVE
Although monitoring of cyclosporin (CsA) is standard clinical practice postrenal transplantation, mycophenolic acid (MPA) concentrations are not routinely measured. There is evidence that a relationship exists between MPA area under the concentration-time curve (AUC) and rejection. In this study, a retrospective analysis was undertaken of 27 adult renal transplant recipients.


METHODS
Patients received CsA and MPA therapy and had a four-point MPA AUC investigation. The relationship between MPA AUC performed in the first week after transplantation, as well as median trough cyclosporin concentrations, and clinical outcomes in the first month posttransplant were evaluated.


RESULTS
A total of 12 patients experienced biopsy proven rejection (44.4%) and 4 patients had gastrointestinal adverse events (14.8%). A statistically significant relationship was observed between the incidence of biopsy proven rejection and both MPA AUC (p = 0.02) and median trough CsA concentration (p = 0.008). No relationship between trough MPA concentration and rejection was observed (p = 0.21). Only 3 of 11 (27%) patients with an MPA AUC > 30 mg x h/L and a median trough CsA > 175 microg/L experienced acute rejection, compared with a 56% incidence of rejection for the remaining 16 patients. Patients who experienced adverse gastrointestinal events had significantly lower MPA AUC (p = 0.04), but median trough CsA concentrations were not significantly different (p = 0.24). Further, 3 of these 4 patients had rejection episodes.


CONCLUSIONS
In addition to standard CsA monitoring, we propose further investigation of the use of a 4-point sampling strategy to predict MPA AUC in the first week posttransplant, which may facilitate optimization of mycophenolate mofetil dose at a time when patients are most vulnerable to acute rejection.
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba QLD 4102, Brisbane, Australia. peter_pillans@health.qld.gov.au
P I
PI
Pillans
R J
RJ
Rigby
P
P
Kubler
C
C
Willis
P
P
Salm
S E
SE
Tett
P J
PJ
Taylor
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology*; D004064:Digestive System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000494:pharmacology*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid