*Purpose: In recent years, significant improvement in organ transplant outcomes have been achieved by using multidrug therapy with several immune monitoring, but the complexity of assessing each drug interactions, including drug blood concentrations, has become a clinical problem. Area Under the Curve (AUC), one of the pharmacokinetic (PK) parameters, is an useful marker of bioavailability in determining the dosage of immunosuppressants. However, due to operational, financial, and patient burden, it is difficult to perform therapeutic drug monitoring for all patients as a practical matter.

*Methods: To evaluate the validity of AUC in optimizing the dose of immunosuppressants, we conducted a retrospective observational study of 204 living donor kidney transplants performed at our institution between July 2012 and October 2020, using the clinical course as an index. In the PK study conducted in the early postoperative period (1 month) and in the maintenance period (after 3 months) at our hospital, and we examined the correlation between AUC and C0, C1, and C2 of CNI (CSA, TAC), MMF, and EVR, respectively, and their association with clinical events.

*Results: Although there was a strong correlation between C2 and AUC of CSA and TAC (r=0.82 and 0.83 in early period: r=0.79 and 0.89 in maintenance period, respectively), there was no correlation between C0 and AUC (r=0.45 and 0.26 in early period: r=0.39 and 0.58 in maintenance period, respectively), indicating that maintenance of CNI by C0 alone is insufficient to control immunosuppressants. On the other hand, no correlation between C0, C1, and C2 and AUC was observed for MMF monitoring in both the early postoperative and maintenance phases (r=all less than 0.6), suggesting that adjusting MMF by AUC is essential for proper management. In the clinical course of the 156 patients who could be followed, de novo DSA was produced in 25 patients in spite of appropriate AUC control by PK study. Furthermore, there were 37 cases of post-transplant infections requiring hospitalization were observed, and bacterial urinary tract infections were the most prevalent. In patients with post-transplant infections, the group with high AUC despite low C0 in MMF, bacterial infections were found in 9 of 13 patients (69.2%) and viral infections in 16 of 35 patients (45.7%). This result suggested the importance of AUC measurement because only C0 control may result in over-immunosuppression in MMF control.

*Conclusions: This study revealed that AUC measurement is useful due to the effects of drug malabsorption and delayed absorption, and that it is important to perform PK analysis for CNI as well as MMF periodically for appropriate management of immunosuppressants.

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