*Purpose: To monitor blood concentration of immunosuppressants, therapeutic drug monitoring (TDM) is required at any point after kidney transplantation (KT) to prevent kidney graft from acute or chronic rejection and minimize drug-induced adverse events (AE). Area under curve (AUC) calculated from multipoint TDM is ideal for this drug monitoring but difficult to perform in any institution. In addition, drug absorption would be affected in patients with diabetes mellitus (DM) due to concomitant intestinal hypomobility. MMF, in part, which undergoes enterohepatic circulation as a metabolic pathway, might to be tough to maintain within target therapeutic range, however; the real behavior in diabetic patients has not been fully studied. We herein investigated the difference of drug absorption and real dose of MMF between diabetic and non-diabetic KT recipients.

*Methods: A total of 172 patients who underwent KT at our hospital from 2015 to 2020 were enrolled in this study. They were divided into 2 groups with or without DM (n=37, n=135, respectively) Initial MMF-TDM by multipoint blood sampling was performed 1W after KT, then oral dose was adjusted according to AUC using the trapezoid method. Further TDMs were performed at 1M and 12M after KT together with kidney graft biopsy. The target range of MPA-AUC were more than 60 and 30mg•hr/L at 1M and 12M, respectively. We investigated the dose of MMF, the chronic graft damage using Banff chronicity score sum and AE represented by over-immunosuppression using urinary decoy cell appearance at 12M.

*Results: In both months post KT, DM Group required higher dose of MMF than that in non-DM in any periods such as diurnal (DIU) or nocturnal period (NOC) to achieve target range of MPA-AUC (Fig.1). In diurnal period, although MPA-AUC was equivalent in both groups at 1M, that in DM Group was significantly lower than that in non-DM Group at 12M. (Fig.2) In contrast, nocturnal MPA-AUC in DM group was significantly higher at 1M, while it became similar at 12M. Despite of significant difference in dose of MMF, there was no difference in the Banff chronicity score sum (cg+cv+ptc) in graft (Fig. 3) as well as the appearance of urinary decoy cell in both groups at 12M. (Fig. 4).

*Conclusions: Diabetic KT recipients required a larger amount (roughly, 30% up-dosing) of MMF to obtain the same target level as that in non-DM recipients. Although MPA-AUC in DM group tended to be lower than that in non-DM group, Diabetic KT recipients achieved comparable outcome without rejection and over-immunosuppression by adjusting doses.

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