P KOTAGIRI1, R MASTERSON1, P HUGHES1, K BARRACLOUGH1
1Royal Melbourne Hospital, Parkville, Australia
Aim: To examine for associations between mycophenolic acid (MPA) exposure at week 5 (w5) and month 3 (m3) post-kidney transplant and clinical outcomes in recipients treated with mycophenolate mofetil (MMF), tacrolimus and prednisolone.
Background: RCT data supports a MPA AUC0-12 target of 30-60mg·h/L early post-kidney transplant. A single study has suggested AUC0-12 should remain >30mg·h/L for the entire first year but the majority in this trial received cyclosporine and had corticosteroids withdrawn.
Methods: This retrospective study involved individuals transplanted between 2015-2017 who had MPA AUC0-12 estimated at w5 and m3. Outcomes examined included rejection, neutropenia, anaemia, diarrhoea, BK and CMV viremia and infections requiring hospitalisation.
Results: 216 individuals were studied. Rejection after the first month was seen in 18% and was more frequent with a w5 AUC0-12 <20mg·h/L (80% vs. 20%; p=0.002). Using multivariate logistic regression, a w5 AUC0-12 <20mg·h/L was independently predictive of subsequent rejection AOR 25.2 (95%CI 2.5,252.3;p=0.006). Neutropenia occurred in 26% and was more frequent with a w5 MPA AUC0-12 >40mg·h/L (32% vs. 19%;p=0.05), and was even more pronounced when AUC0-12 cut-off values of 50mg·h/L and 60mg·h/L were considered (48% vs. 16%,p<0.001; and 56% vs. 19%,p<0.001). Similarly, neutropenia was more frequent with a m3 AUC0-12 >40mg·h/L (45% vs. 25%;p=0.02), with the proportion affected again increasing with higher AUC0-12 cut-off values No associations were observed between m3 AUC0-12 and rejection or w5 or m3 AUC0-12 and any other toxicities examined.
Conclusions: These data suggest 20mg·h/L might be an appropriate minimum target at w5 in individuals receiving MMF, tacrolimus and steroids. However, larger studies are needed. The increased neutropenia seen with increasing MPA AUC0-12 highlights the importance of balancing risks of under and over-exposure.
Renal Registrar at the Royal Melbourne Hospital