UTILITY OF MYCOPHENOLIC ACID AREA UNDER THE CURVE (MPA-AUC) AFTER MYCOPHENOLATE MOFETIL DOSE REDUCTION (MMF-DR) IN KIDNEY TRANSPLANT RECIPIENTS

A Malaweera1, A Ellis3, A Frauman3, D Lee1,2

1Department of Renal Medicine, Eastern Health, 2Eastern Health Clinical School, Monash University, 3Clinical Pharmacology and Therapeutics, Austin Health

Aims: To examine the utility of mycophenolic acid area under the curve (MPA-AUC) after mycophenolate mofetil dose reduction (MMF-DR) in kidney transplant recipients (KTR).

Background: The benefit of concentration-controlled dosing versus fixed dosing of MMF remains controversial, with data lacking for tacrolimus-based regimen. Universal MPA-AUC is labour intensive. We examined our approach of targeted MPA-AUC testing on KTR requiring MMF-DR to tailor subsequent MMF dosing since 2016.

Methods: We performed a retrospective single centre analysis on KTR (01/03/2012-29/02/2020) on tacrolimus, MMF and prednisolone who required MMF-DR (defined as <1500 mg/day within the first 12 months). We analysed estimated MPA-AUCt0-12 using trapezoid method following MMF-DR and compared the subsequent rejection rates at 12 months with or without MPA-AUC testing.

Results: 117 of 185 KTR (63%) required MMF-DR, of whom 71 (61%) had MPA-AUC testing. 73% were due to neutropenia. At 500mg BD (n=62), 39 (63%), 20 (32%), 2 (3%) and 1 (2%) had an MPA-AUC of 30-60mg.h/L, 20-29.9mg.h/L, >60 mg.h/L and invalid (due to early peak) respectively. At 250mg BD (n=9), 4 (44%), 2 (22%) and 3 (33%) had an MPA-AUC of 30-60mg.h/L, 20-29.9mg.h/L and <20mg.h/L respectively. 12 KTR (17%) had MMF dose adjusted based on MPA-AUC result (n=6 increased, n=6 decreased). Excluding KTR with early rejection within the first month, there was no significant difference in subsequent rejection rates following MMF-DR with or without MPA-AUC testing (2/44 (4.6%) versus 6/44 (13.6%); P=0.14).

Conclusion: Although the majority of KTR achieved a traditional therapeutic MPA-AUC range of 30-60mg.h/L following MMF-DR, it did alter decision-making on subsequent MMF dosing in some KTR. A larger prospective study is warranted to examine this targeted approach on clinical outcomes.


Biography:

I am currently a first year Nephrology Advanced trainee at Eastern Health and will be continuing my second year at Monash Health.
I completed my undergraduate medical degree at Cardiff university in the UK in 2011. After this, I completed my internship and medical training in London where I completed all three parts of the Membership of Royal College of Physicians Exams (MRCP)
Once I came to Australia, I completed Basic Physicians training and one year of advanced training in general medicine after completing the Royal College of Physicians exams.

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