Association between Trough Mycophenolic Acid Concentration and Clinical Events in Live Donor Kidney Transplant Recipients

Introduction:

Mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil (MMF), is used as maintenance immunosuppressant in solid organ transplantation.  Therapeutic drug monitoring of MPA is recommended due to large inter-patient variabilities and strong association between MPA exposure and clinical events. 

Objectives:

The present study was conducted to assess the correlation between trough MPA level and clinical outcomes in live donor kidney transplant recipients. 

Study Design:

This was single centre non-randomized longitudinal prospective open-label study.

Methods: A total of 104 live donor allograft recipients were enrolled from Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India.  MPA levels were measured on post transplant day 0 and 7 and months 1,3,6,9 and 12. Altogether, 582 samples were analyzed for trough MPA level by HPLC.

Results: Twenty (19.2%) episodes of acute rejection (AR) were reported in study cohort. Mean trough MPA levels were significantly lower in patients with acute rejection (AR) compared with rejection free patients (1.61mg/l versus 2.15mg/l; p< 0.05). Likewise, Trough MPA levels were also significantly higher in patients with MPA related adverse events such as leucopenia (3.28mg/l versus 1.89mg/l; p<0.001), GI adverse events (3.15mg/l versus 2mg/l; p< 0.05; GI AEs) and infections (2.25mg/l versus 1.88mg/l; p< 0.05) compared to patients without leucopenia, GI AEs and infection, respectively. Receiver operating curve analysis revealed trough MPA levels 1.60 mg/l best discriminate patients with and without AR, and MPA level 3 mg/l best differentiate patients with and without adverse events.

Conclusions:

The present study demonstrates significant relationship between trough MPA levels and clinical events. Fixed dose regimen was associated with low trough MPA levels during initial period of transplantation and hence additional risk of AR due to under exposure of MPA. This study recommended patients with MPA related AEs such as leucopenia or GI AEs could be benefited, from concentration controlled MMF dose regimen.