Background: Donor-specific antibody (DSA) formation is a key factor in development of antibody-mediated rejection and irreversible renal dysfunction. Prevention of DSA formation is critical, mandating therapeutic levels of all immunosuppressive agents, including MMF. Measurement of 2 hour MPA AUC levels provides precise and feasible assessment of the adequacy of individual MMF dosage. This was a retrospective study to determine if aggressive monitoring of MPA AUC levels and optimizing MMF therapy would affect formation of DSA.
Methods: Between October 2010 and November 2012, MPA AUC testing was performed on 264 DSA-negative renal transplant patients. Group 1 (clinical): 201 patients post-transplant>1 year (range 1-11 years) underwent MPA AUC testing for clinical indication (increased serum creatinine, increased immune cell function, side effects associated with MMF). Group 2 (preemptive): from May 2011-November 1, 2012, 63 patients post transplant < 1 year underwent preemptive AUC testing. Patients in both groups were assessed for MMF dosage, MPA AUC levels and DSA status.
Results: Group 1: at time of initial MPA AUC testing, 108 (54%) patients had subtherapeutic MPA AUC levels (<60). Dose adjustment was made in all patients who could tolerate higher doses and repeat MPA AUC testing was performed in 42 patients:
|n=42||Initial testing||Post-dosage change||p value|
|MMF Dose (mg/d)±SEM||1192±90||1884±102||<0.0001|
|MPA AUC(mg h/L)±SEM||41.90±1.59||64.02±2.56||<0.0001|
To date, 130 patients in Group 1 have undergone repeat testing for DSA (including 27/42 patients with initially subtherapeutic MPA AUC): all remain DSA negative.
Group 2: all patients underwent initial MPA AUC testing within 9 months of transplant. At initial testing, 13 (21%) patients had MPA AUC < 60, dose adjustment was made and repeat MPA AUC testing was performed:
|n=13||Initial testing||Post-dosage change||p value|
|MMF Dose (mg/d)±SEM||1194±98||1731±196||<0.0001|
|MPA AUC(m h/ L)±SEM||45.97±4.02||68.15±2.39||<0.0001|
To date, 36 patients in Group 2 have undergone repeat testing for DSA (including 9/13 patients with initially subtherapeutic MPA AUC): all remain DSA negative.
Conclusions: 1.There is an unexpectedly high incidence of inadequate MMF dosing, even within the first year of renal transplantation. 2. Aggressive and preemptive MPA AUC monitoring ensures therapeutic MMF dosing and results in low if not absent DSA formation in both established and de novo renal transplant patients.
To cite this abstract in AMA style:Waybill M, Narins S, Scott R, Yang H. Therapeutic Mycophenolic Acid Area-Under-Curve (MPA AUC) Levels Abolish Donor-Specific Antibody Formation in Established and De Novo Renal Transplant Patients [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/therapeutic-mycophenolic-acid-area-under-curve-mpa-auc-levels-abolish-donor-specific-antibody-formation-in-established-and-de-novo-renal-transplant-patients/. Accessed September 23, 2017.
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