Inadequate mycophenolic acid exposure and acute rejection in kidney transplantation.
BACKGROUND
The clinical utility of predose levels of mycophenolic acid (MPA) monitoring among patients treated with mycophenolate mofetil (MMF) has been questioned. The aim of this study was to evaluate the impact of adequate MPA levels in the incidence of acute rejection episodes among a cohort of kidney transplant recipients.


METHODS
In this retrospective study of 314 consecutive cases treated with tacrolimus, MMF, and steroids, evaluated 12-hour trough MPA samples during the first week as well as at 1, 3, 6, and 12 months as median values.


RESULTS
During the first week, the median values of MPA were 1.6 microg/mL (p25-75 0.7-2.7 microg/mL) on mean doses of 1.84 +/- 0.38 g/d. The incidence of acute rejection was 28%. The mean MPA levels during the first week were significantly lower among patients who developed rejection than in nonrejectors (1.5 +/- 0.1 vs 2.1 +/- 0.1 microg/mL; P < .001). There were no significant differences in trough tacrolimus levels between rejectors and nonrejectors (11.2 +/- 0.4 vs 11.6 +/- 1.2 microg/mL; P < .78). Logistic regression analysis showed that one of the predictive factors of acute rejection was a 12-hour trough MPA <1.6 microg/mL (relative risk [RR] 2.6; CI [confidence interval] 95% 1.6-4.3; P < .001).


CONCLUSIONS
Adequate MPA exposure is important to prevent acute rejection. Taking into account that the routine measurement of the area under the curve of MPA is impractical, at least the follow-up of trough MPA levels may help in the management of renal transplant recipients.
Sánchez-Fructuoso
A I
AI
Department of Nephrology, Hospital Clínico San Carlos, Madrid, Spain. sanchezfruct@telefonica.net
de la Higuera
M A M
MA
Giorgi
M
M
Ramos
F
F
Garcia Ledesma
P
P
Calvo
N
N
Pérez-Flores
I
I
Barrientos
A
A
D000208:Acute Disease; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D009173:Mycophenolic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid